Serum biomarkers in lung cancer

• US 20060223127A1
• Filed: 12/16/2003
• Published: 10/05/2006
• Est. Priority Date: 12/18/2002
• Status: Active Grant

• Current Assignee: Queen Elizabeth Hospital (Meridian Hospital Co. Plc), Vermillion, Inc.
• Original Assignee: Ciphergen Biosystems Incorporated, Queen Elizabeth Hospital (Meridian Hospital Co. Plc)
• Inventors: Yip, Victor F., Yip, Christine L., Cho, Chi Shing, Yip, Timothy Tak Chun, Au, Siu Kie, Yip, Tai-Tung
• Granted Patent: US 8,014,952 B2
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G01N 33/6851 Methods of protein analysis involving laser desorption ionisation mass spectrometry
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations

Abstract

Certain biomarkers and biomarker combinations are useful in a qualifying lung cancer status in a subject. A diagnostic methodology employing these biomarkers and combinations can detect whether a subject has lung cancer.

Claims

1. A method for qualifying lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a diagnostic level of a protein selected from either a first group consisting of

(i) IM-522, IM-273, IM-520, IM-519, IM-454, IM-507, IM-521, IM-148, IM-266, IM-537, N-471, IM-510, IM-544, IM-474, IM-155, IM-157, IM-176, IM-445, IM-177, IM-440, IM-468, IM-438, IM-547, IM-359, IM-436, IM-106, IM-455, IM-444, IM-158, IM-265, IM-50, IM-159, IM-156, IM-439, IM-157, IM-508, IM-514, IM-478, IM-473, IM-360, IM-435, IM-150, IM-151, IM-110, IM-51, IM-163, IM-437, IM-546, IM-153, and IM-268,

or from a second group consisting of

(ii) WM-61, WM-447, WM-446, WM-133, WM-119, WM-278, WM-134, WM-363, WM-282, WM-362, WM-120, WM-290, WM-65, WM-277, WM-70, WM-369, WM-17, WM-473, WM-47, WM-203, WM-276, WM-279, WM-62, WM-366, WM-456, WM-428, WM-384, WM-287, WM-420, WM-292, WM-431, WM-455, WM-20, WM-340, WM-105, WM-389, WM-63, WM-354, WM-450, WM-466, WM-296, WM-343, WM-341, WM-339, WM-55, WM-66, WM-48, WM-38, WM-138, and WM-310,

wherein the biomarker is differentially present in samples of a subject with lung cancer and a normal subject that is free of lung cancer.

2. The method according to claim 1, wherein the protein is selected from either a first group consisting of

(i) IM-522, IM-273, IM-520, IM-519, IM-454, IM-507, IM-521, IM-148, IM-266, IM-537, IM-471, IM-510, IM-544, IM-474, and IM-155,

or from a second group consisting of

(ii) WM-61, WM-447, WM-446, WM-133, WM-119, WM-278, WM-134, WM-363, WM-282, WM-362, WM-120, WM-290, WM-65, WM-277, and WM-70.

3. The method according to claim 1, wherein the protein is selected from either a first group consisting of

(i) IM-522, IM-273, IM-520, IM-519, and IM-454,

or from a second group consisting

(ii) WM-61, WM-447, WM-446, WM-133, and WM-119.

4. The method according to claim 1, which uses a single biomarker selected from the group consisting of the WM-446 and WM-447.

5. A method for qualifying lung carcinoma risk in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of

(i) IM-522, IM-273, IM-520, IM-519, IM-454, IM-507, IM-521, IM-148, IM-266, IM-537, IM-471, I-510, IM-544, IM-474, IM-155, IM-157, IM-176, IM-445, IM-177, IM-440, IM-468, IM-438, IM-547, IM-359, IM-436, IM-106, IM-455, IM-444, IM-158, IM-265, IM-50, IM-159, IM-156, IM-439, IM-157, IM-508, IM-514, IM-478, IM-473, IM-360, IM-435, IM-150, IM-151, IM-110, IM-51, IM-163, IM-437, IM-546, IM-153, and IM-268,

or from a second group consisting of

(ii) WM-61, WM-447, WM-446, WM-133, WM-119, WM-278, WM-134, WM-363, WM-282, WM-362, WM-120, WM-290, WM-65, WM-277, WM-70, WM-369, WM-17, WM-473, WM-47, WM-203, WM-276, WM-279, WM-62, WM-366, WM-456, WM-428, WM-384, WM-287, WM-420, WM-292, WM-431, WM-455, WM-20, WM-340, WM-105, WM-389, WM-63, WM-354, WM-450, WM-466, WM-296, WM-343, WM-341, WM-339, WM-55, WM-66, WM-48, WM-38, WM-138, and WM-310.

6. The method according to claim 5, wherein the pattern-recognition analysis is keyed to a pair of peaks selected either from a first group consisting of

(i) IM-266 and IM-474, IM-266 and IM-38, IM-266 and IM-454, IM-266 and IM-522, IM-266 and IM-544, IM-266 and IM-471, IM-474 and IM-151, IM-474 and IM-156, IM-474 and IM-544, IM-474 and IM-38, IM-522 and IM-507, IM-522 and IM-156, and IM-522 and IM-440;

or from a second group consisting of

(ii) WM-447 and WM-59, WM-447 and WM-19, WM-447 and WM-118, WM-447 and WM-473, WM-19 and WM-59, WM-19 and WM-473, WM-19 and WM-369, WM-61 and WM-154, WM-61 and WM-369, WM-118 and WM-59 and WM-282 and WM-127.

7. The method according to claim 5, wherein the pattern-recognition analysis is keyed to a pair of peaks selected from either a first group consisting of

(i) IM-266 and IM-474, IM-266 and IM-544, and IM-156 and IM-522;

or from a second group consisting of

(ii) WM-447 and WM-59, WM-447 and WM-19, and WM-19 and WM-59.

8. The method according to claim 5, wherein the pattern-recognition analysis is keyed to a triplet of peaks selected from

(i) IM-266, IM-454 and IM-474;

and IM-266, IM-474 and IM-544;

or wherein the analysis is keyed to

(ii) WM-447, WM-19 and WM-473.

9. A kit for detecting and diagnosing lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers selected from either a first group consisting of

(i) IM-522, IM-273, IM-520, IM-519, IM-454, IM-507, IM-521, IM-148, IM-266, IM-537, I-471, IM-510, IM-544, IM-474, IM-155, IM-157, IM-176, IM-445, IM-177, IM-440, IM-468, IM-438, IM-547, IM-359, IM-436, IM-106, IM-455, IM-444, IM-158, IM-265, IM-50, IM-159, IM-156, IM-439, IM-157, IM-508, IM-514, IM-478, IM-473, IM-360, IM-435, IM-150, IM-151, IM-110, IM-51, IM-163, IM-437, IM-546, IM-153, and IM-268,

or from a second group consisting of

(ii) WM-61, WM-447, WM-446, WM-133, WM-119, WM-278, WM-134, WM-363, WM-282, WM-362, WM-120, WM-290, WM-65, WM-277, WM-70, WM-369, WM-17, WM-473, WM-47, WM-203, WM-276, WM-279, WM-62, WM-366, WM-456, WM-428, WM-384, WM-287, WM-420, WM-292, WM-431, WM-455, WM-20, WM-340, WM-105, WM-389, WM-63, WM-354, WM-450, WM-466, WM-296, WM-343, WM-341, WM-339, WM-55, WM-66, WM-48, WM-38, WM-138, and WM-310, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

10. A kit according to claim 9, further comprising a washing solution or instructions for making a washing solution.

11. A kit according to claim 9, wherein the substrate is a SELDI probe that comprises either (i) functionalities that adsorb transition metal ions by chelation or (ii) functionalities that allow for cation exchange.

12. A method for qualifying lung adenocarcinoma status in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290, WM-363, WM-133, WM-341, WM-285, WM-366, WM-282, WM-362, WM-310, WM-292, WM-120, WM-134, WM-276, WM-428, WM-277, WM-20, WM-119, WM-340, WM-48, WM-389, WM-450, WM-47, WM-343, WM-17, WM-583, WM-70, WM-706, WM-346, WM-466, WM-646, WM-384, WM-336, WM-294, WM-339, WM-473, WM-369, WM-38, WM-283, WM-685, WM-66, WM-55, WM-650, WM-307, WM-278, WM-342, and WM-429.

13. The method according to claim 12, wherein the protein is selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290, WM-363, WM-133, WM-341, WM-285, WM-366, WM-282, WM-362, WM-310, WM-292, and WM-120.

14. The method according to claim 12, wherein the protein is selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290.

15. A method for qualifying status of lung adenocarcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of WM-447, WM-652, WM-61, WM-446, WM-290, WM-363, WM-133, WM-341, WM-285, WM-366, WM-282, WM-362, WM-310, WM-292, WM-120, WM-134, WM-276, WM-428, WM-277, WM-20, WM-119, WM-340, WM-48, WM-389, WM-450, WM-47, WM-343, WM-17, WM-583, WM-70, WM-706, WM-346, WM-466, WM-646, WM-384, WM-336, WM-294, WM-339, WM-473, WM-369, WM-38, WM-283, WM-685, WM-66, WM-55, WM-650, WM-307, WM-278, WM-342, and WM-429.

16. The method according to claim 15, wherein the protein is selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290, WM-363, WM-133, WM-341, WM-285, WM-366, WM-282, WM-362, WM-310, WM-292, and WM-120.

17. The method according to claim 15, wherein the protein is selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290.

18. A kit for detecting and diagnosing lung adenocarcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of biomarkers selected from the group consisting of WM-447, WM-652, WM-61, WM-446, WM-290, WM-363, WM-133, WM-341, WM-285, WM-366, WM-282, WM-362, WM-310, WM-292, WM-120, WM-134, WM-276, WM-428, WM-277, WM-20, WM-119, WM-340, WM-48, WM-389, WM-450, WM-47, WM-343, WM-17, WM-583, WM-70, WM-706, WM-346, WM-466, WM-646, WM-384, WM-336, WM-294, WM-339, WM-473, WM-369, WM-38, WM-283, WM-685, WM-66, WM-55, WM-650, WM-307, WM-278, WM-342, and WM-429, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

19. A kit according to claim 18, further comprising a washing solution or instructions for making a washing solution.

20. A kit according to claim 18, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

21. A method for qualifying squamous cell lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-447, WM-61, WM-277, WM-446, WM-133, WM-134, WM-363, WM-362, WM-276, WM-706, WM-203, WM-466, WM-366, WM-65, WM-70, WM-341, WM-429, WM-347, WM-17, WM-47, WM-431, WM-62, WM-473, WM-384, WM-438, WM-652, WM-282, WM-389, WM-290, WM-278, WM-456, WM-673, WM-340, WM-55, WM-455, WM-645, WM-138, WM-420, WM-450, WM-369, WM-279, WM-342, WM-471, WM-674, WM-120, WM-20, WM-287, WM-83, WM-154, and WM-128.

22. The method according to claim 21, wherein the protein is selected from the group consisting of WM-447, WM-61, WM-277, WM-446, WM-133, WM-134, WM-363, WM-362, WM-276, WM-706, WM-203, WM-466;

WM-366, WM-65, and WM-70.

23. The method according to claim 21, wherein the protein is selected from the group consisting of WM-447, WM-61, WM-277, WM-446, and WM-133.

24. A method for qualifying status of squamous cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of WM-447, WM-61, WM-277, WM-446, WM-133, WM-134, WM-363, WM-362, WM-276, WM-706, WM-203, WM-466, WM-366, WM-65, WM-70, WM-341, WM-429, WM-347, WM-17, WM-47, WM-431, WM-62, WM-473, WM-384, WM-438, WM-652, WM-282, WM-389, WM-290, WM-278, WM-456, WM-673, WM-340, WM-55, WM-455, WM-645, WM-138, WM-420, WM-450, WM-369, WM-279, WM-342, WM-471, WM-674, WM-120, WM-20, WM-287, WM-83, WM-154, and WM-128.

25. The method according to claim 24, wherein the protein is selected from the group consisting of WM-447, WM-61, WM-277, WM-446, WM-133, WM-134, WM-363, WM-362, WM-276, WM-706, WM-203, WM-466, WM-366, WM-65, and WM-70.

26. The method according to claim 24, wherein the protein is selected from the group consisting of WM-447, WM-61, WM-277, WM-446, and WM-133.

27. A kit for detecting and diagnosing squamous cell lung carcinoma, comprising

(A) all adsorbent attached to a substrate that retains one or more of the biomarkers selected from the group consisting of WM-447, WM-61, WM-277, WM-446, WM-133, WM-134, WM-363, WM-362, WM-276, WM-706, WM-203, WM-466, WM-366, WM-65, WM-70, WM-341, WM-429, WM-347, WM-17, WM-47, WM-431, WM-62, WM-473, WM-384, WM-438, WM-652, WM-282, WM-389, WM-290, WM-278, WM-456, WM-673, WM-340, WM-55, WM-455, WM-645, WM-138, WM-420, WM-450, WM-369, WM-279, WM-342, WM-471, WM-674, WM-120, WM-20, WM-287, WM-83, WM-154, and WM-128, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

28. A kit according to claim 27, further comprising a washing solution or instructions for making a washing solution.

29. A kit according to claim 27, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

30. A method for qualifying small cell lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-70, WM-706, WM-369, WM-447, WM-61, WM-652, WM-282, WM-446, WM-456, WM-134, WM-203, WM-646, WM-455, WM-65, WM-685, WM-473, WM-343, WM-466, WM-341, WM-340, WM-363, WM-339, WM-457, WM-86, WM-506, WM-72, WM-287, WM-82, WM-528, WM-85, WM-73, WM-138, WM-384, WM-83, WM-450, WM-310, WM-277, WM-79, WM-207, WM-278, WM-290, WM-366, WM-472, WM-420, WM-147, WM-55, WM-669, WM-357, WM-429, and WM-279.

31. The method according to claim 30, wherein the protein is selected from the group consisting of WM-70, WM-706, WM-369, WM-447, WM-61, WM-652, WM-282, WM-446, WM-456, WM-134, WM-203, WM-646, WM-455, WM-65, and WM-685.

32. The method according to claim 30, wherein the protein is selected from the group consisting of WM-70, WM-706, WM-369, WM-447, and WM-61.

33. A method for qualifying status of small cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of WM-70, WM-706, WM-369, WM-447, WM-61, WM-652, WM-282, WM-446, WM-456, WM-134, WM-203, WM-646, WM-455, WM-65, WM-685, WM-473, WM-343, WM-466, WM-341, WM-340, WM-363, WM-339, WM-457, WM-86, WM-506, WM-72, WM-287, WM-82, WM-528, WM-85, WM-73, WM-138, WM-384, WM-83, WM-450, WM-310, WM-277, WM-79, WM-207, WM-278, WM-290, WM-366, WM-472, WM-420, WM-147, WM-55, WM-669, WM-357, WM-429, and WM-279.

34. The method according to claim 33, wherein the protein is selected from the group consisting of WM-70, WM-706, WM-369, WM-447, WM-61, WM-652, WM-282, WM-446, WM-456, WM-134, WM-203, WM-646, WM-455, WM-65, and WM-685.

35. The method according to claim 33, wherein the protein is selected from the group consisting of WM-70, WM-706, WM-369, WM-447, and WM-61.

36. A kit for detecting and diagnosing small cell lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers selected from the group consisting of WM-70, WM-706, WM-369, WM-447, WM-61, WM-652, WM-282, WM-446, WM-456, WM-134, WM-203, WM-646, WM-455, WM-65, WM-685, WM-473, WM-343, WM-466, WM-341, WM-340, WM-363, WM-339, WM-457, WM-86, WM-506, WM-72, WM-287, WM-82, WM-528, WM-85, WM-73, WM-138, WM-384, WM-83, WM-450, WM-310, WM-277, WM-79, WM-207, WM-278, WM-290, WM-366, WM-472, WM-420, WM-147, WM-55, WM-669, WM-357, WM-429, and WM-279, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

37. A kit according to claim 36, further comprising a washing solution or instructions for making a washing solution.

38. A kit according to claim 36, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

39. A method for qualifying non-small cell lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-341, WM-342, WM-343, WM-48, WM-340, WM-346, WM-47, WM-339, WM-389, WM-669, WM-447, WM-652, WM-154, WM-587, WM-456, WM-450, WM-283, WM-207, WM-436, WM-384, WM-61, WM-167, WM-382, WM-285, WM-650, WM-203, WM-119, WM-282, WM-686, WM-383, WM-429, WM-11, WM-208, WM-451, WM-473, WM-220, WM-685, WM-338, WM-71, WM-266, WM-70, WM-545, WM-675, WM-446, WM-120, WM-267, WM-466, WM-347, WM-153, and WM-38.

40. The method according to claim 39, wherein the protein is selected from the group consisting of WM-341, WM-342, WM-343, WM-48, WM-340, WM-346, WM-47, WM-339, WM-389, WM-669, WM-447, WM-652, WM-154, WM-587, and WM-456.

41. The method according to claim 39, wherein the protein is selected from the group consisting of WM-341, WM-342, WM-343, WM-48, and WM-340.

42. A method for qualifying status of non-small cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from the group consisting of WM-341, WM-342, WM-343, WM-48, WM-340, WM-346, WM-47, WM-339, WM-389, WM-669, WM-447, WM-652, WM-154, WM-587, WM-456, WM-450, WM-283, WM-207, WM-436, WM-384, WM-61, WM-167, WM-382, WM-285, WM-650, WM-203, WM-119, WM-282, WM-686, WM-383, WM-429, WM-11, WM-208, WM-451, WM-473, WM-220, WM-685, WM-338, WM-71, WM-266, WM-70, WM-545, WM-675, WM-446, WM-120, WM-267, WM-466, WM-347, WM-153, and WM-38.

43. The method according to claim 42, wherein the protein is selected from the group consisting of WM-341, WM-342, WM-343, WM-48, WM-340, WM-346, WM-47, WM-339, WM-389, WM-669, WM-447, WM-652, WM-154, WM-587, and WM-456.

44. The method according to claim 42, wherein the protein is selected from the group consisting of WM-341, WM-342, WM-343, WM-48, and WM-340.

45. A kit for detecting and diagnosing non-small cell lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers WM-341, WM-342, WM-343, WM-48, WM-340, WM-346, WM-47, WM-339, WM-389, WM-669, WM-447, WM-652, WM-154, WM-587, WM-456, WM-450, WM-283, WM-207, WM-436, WM-384, WM-61, WM-167, WM-382, WM-285, WM-650, WM-203, WM-119, WM-282, WM-686, WM-383, WM-429, WM-11, WM-208, WM-451, WM-473, WM-220, WM-685, WM-338, WM-71, WM-266, WM-70, WM-545, WM-675, WM-446, WM-120, WM-267, WM-466, WM-347, WM-153, and WM-38, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

46. A kit according to claim 45, further comprising a washing solution or instructions for making a washing solution.

47. A kit according to claim 45, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

48. A method for qualifying large cell lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, WM-447, WM-684, WM-183, WM-190, WM-686, WM-397, WM-466, WM-20, WM-17, WM-545, WM-47, WM-191, WM-147, WM-480, WM-590, WM-218, WM-285, WM-652, WM-651, WM-366, WM-403, WM-418, WM-430, WM-456, WM-714, WM-646, WM-109, WM-302, WM-587, WM-375, WM-131, WM-706, WM-398, WM-309, WM-55, and WM-488.

49. The method according to claim 48, wherein the protein is selected from the group consisting of WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, and WM-447.

50. The method according to claim 48, wherein the protein is selected from the group consisting of WM-16, WM-26, WM-499, WM-134, and WM-647.

55. A kit according to claim 50, further comprising a washing solution or instructions for making a washing solution.

56. A kit according to claim 50, Wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

51. A method for qualifying status of large cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from the group consisting of WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, WM-447, WM-684, WM-183, WM-190, WM-686, WM-397, WM-466, WM-20, WM-17, WM-545, WM-47, WM-191, WM-147, WM-480, WM-590, WM-218, WM-285, WM-652, WM-651, WM-366, WM-403, WM-418, WM-430, WM-456, WM-714, WM-646, WM-109, WM-302, WM-587, WM-375, WM-131, WM-706, WM-398, WM-309, WM-55, and WM-488.

52. The method according to claim 51, wherein the protein is selected from the group consisting of WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, and WM-447.

53. The method according to claim 51, wherein the protein is selected from the group consisting of WM-16, WM-26, WM-499, WM-134, and WM-647.

54. A kit for detecting and diagnosing large cell lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, WM-447, WM-684, WM-183, WM-190, WM-686, WM-397, WM-466, WM-20, WM-17, WM-545, WM-47, WM-191, WM-147, WM-480, WM-590, WM-218, WM-285, WM-652, WM-651, WM-366, WM-403, WM-418, WM-430, WM-456, WM-714, WM-646, WM-109, WM-302, WM-587, WM-375, WM-131, WM-706, WM-398, WM-309, WM-55, and WM-488, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

57. A method for distinguishing lung adenocarcinoma from squamous lung carcinoma in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-62, WM-415, WM-152, WM-385, WM-347, WM-134, WM-36, WM-108, WM-99, WM-151, WM-289, WM-363, WM-61, WM-117, WM-211, WM-362, WM-133, WM-414, WM-277, WM-141, WM-64, WM-135, WM-447, WM-383, WM-338, WM-63, WM-142, WM-446, WM-186, WM-111, WM-445, WM-455, WM-276, WM-444, WM-181, WM-35, WM-285, WM-456, WM-39, WM-82, WM-17, WM-203, WM-83, WM-412, WM-96, WM-74, WM-457, WM-431, WM-340, and WM-49.

58. The method according to claim 57, wherein the protein is selected from the group consisting of WM-62, WM-415, WM-152, WM-385, WM-347, WM-134, WM-36, WM-108, WM-99, WM-151, WM-289, WM-363, WM-61, WM-117, and WM-211.

59. The method according to claim 57, wherein the protein is selected from the group consisting of WM-62, WM-415, WM-152, WM-385, and WM-347.

60. A method for distinguishing lung adenocarcinoma from squamous lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from the group consisting of WM-62, WM-415, WM-152, WM-385, WM-347, WM-134, WM-36, WM-108, WM-99, WM-151, WM-289, WM-363, WM-61, WM-117, WM-211, WM-362, WM-133, WM-414, WM-277, WM-141, WM-64, WM-135, WM-447, WM-383, WM-338, WM-63, WM-142, WM-446, WM-186, WM-111, WM-445, WM-455, WM-276, WM-444, WM-181, WM-35, WM-285, WM-456, WM-39, WM-82, WM-17, WM-203, WM-83, WM-412, WM-96, WM-74, WM-457, WM-431, WM-340, and WM-49.

61. The method according to claim 60, wherein the protein is selected from the group consisting of WM-62, WM-415, WM-152, WM-385, WM-347, WM-134, WM-36, WM-108, WM-99, WM-151, WM-289, WM-363, WM-61, WM-117, and WM-211.

62. The method according to claim 60, wherein the protein is selected from the group consisting of WM-62, WM-415, WM-152, WM-385, and WM-347.

63. A kit for distinguishing lung adenocarcinoma from squamous lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers WM-16, WM-26, WM-499, WM-134, WM-647, WM-277, WM-310, WM-363, WM-446, WM-221, WM-648, WM-657, WM-290, WM-328, WM-447, WM-684, WM-183, WM-190, WM-686, WM-397, WM-466, WM-20, WM-17, WM-545, WM-47, WM-191, WM-147, WM-480, WM-590, WM-218, WM-285, WM-652, WM-651, WM-366, WM-403, WM-418, WM-430, WM-456, WM-714, WM-646, WM-109, WM-302, WM-587, WM-375, WM-131, WM-706, WM-398, WM-309, WM-55, and WM-488, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

64. A kit according to claim 63, further comprising a washing solution or instructions for making a washing solution.

65. A kit according to claim 63, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

66. A method for distinguishing lung adenocarcinoma from small cell lung carcinoma in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-457, WM-72, WM-369, WM-78, WM-79, WM-73, WM-64, WM-320, WM-419, WM-85, WM-82, WM-53, WM-412, WM-440, WM-455, WM-313, WM-456, WM-86, WM-70, WM-246, WM-360, WM-190, WM-418, WM-83, WM-257, WM-138, WM-47, WM-252, WM-282, WM-60, WM-68, WM-325, WM-402, WM-411, WM-405, WM-75, WM-417, WM-387, WM-26, WM-410, WM-420, WM-164, WM-67, WM-66, WM-391, WM-340, WM-428, WM-198, WM-312, and WM-152.

67. The method according to claim 66, wherein the protein is selected from the group consisting of WM-457, WM-72, WM-369, WM-78, WM-79, WM-73, WM-64, WM-320, WM-419, WM-85, WM-82, WM-53, WM-412, WM-440, and WM-455.

68. The method according to claim 66, wherein the protein is selected from the group consisting of WM-457, WM-72, WM-369, WM-78, and WM-79.

69. A method for distinguishing lung adenocarcinoma from small cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of WM-457, WM-72, WM-369, WM-78, WM-79, WM-73, WM-64, WM-320, WM-419, WM-85, WM-82, WM-53, WM-412, WM-440, WM-455, WM-313, WM-456, WM-86, WM-70, WM-246, WM-360, WM-190, WM-418, WM-83, WM-257, WM-138, WM-47, WM-252, WM-282, WM-60, WM-68, WM-325, WM-402, WM-411, WM-405, WM-75, WM-417, WM-387, WM-26, WM-410, WM-420, WM-164, WM-67, WM-66, WM-391, WM-340, WM-428, WM-198, WM-312, and WM-152.

70. The method according to claim 69, wherein the protein is selected from the group consisting of WM-457, WM-72, WM-369, WM-78, WM-79, WM-73, WM-64, WM-320, WM-419, WM-85, WM-82, WM-53, WM-412, WM-440, and WM-455.

71. The method according to claim 69, wherein the protein is selected from the group consisting of WM-457, WM-72, WM-369, WM-78, WM-79.

72. A kit for distinguishing lung adenocarcinoma from small cell lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, WM-447, WM-133, WM-245, WM-52, WM-96, WM-238, WM-243, WM-138, WM-62, WM-580, WM-134, WM-240, WM-256, WM-203, WM-111, WM-95, WM-247, WM-157, WM-242, WM-556, WM-63, WM-239, WM-234, WM-274, WM-370, WM-301, WM-449, WM-74, WM-261, WM-467, WM-237, WM-262, WM-295, WM-288, WM-384, and WM-37, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

73. A kit according to claim 72, further comprising a washing solution or instructions for making a washing solution.

74. A kit according to claim 72, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

75. A method for distinguishing squamous cell lung carcinoma from small cell lung carcinoma in a subject, comprised of analyzing a biological sample from said subject for a level of a protein selected from the group consisting of WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, WM-447, WM-133, WM-245, WM-52, WM-96, WM-238, WM-243, WM-138, WM-62, WM-580, WM-134, WM-240, WM-256, WM-203, WM-111, WM-95, WM-247, WM-157, WM-242, WM-556, WM-63, WM-239, WM-234, WM-274, WM-370, WM-301, WM-449, WM-74, WM-261, WM-467, WM-237, WM-262, WM-295, WM-288, WM-384, and WM-37.

76. The method according to claim 75, wherein the protein is selected from the group consisting of WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, and WM-447.

77. The method according to claim 75, wherein the protein is selected from the group consisting of WM-276, WM-277, WM-362, WM-257, and WM-363.

78. A method for distinguishing squamous cell lung carcinoma from small cell lung carcinoma in a subject, comprising

(A) providing a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, and

(B) extracting data from the spectrum and subjecting the data to pattern-recognition analysis that is keyed to at least one peak selected from either a first group consisting of WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, WM-447, WM-133, WM-245, WM-52, WM-96, WM-238, WM-243, WM-138, WM-62, WM-580, WM-134, WM-240, WM-256, WM-203, WM-111, WM-95, WM-247, WM-157, WM-242, WM-556, WM-63, WM-239, WM-234, WM-274, WM-370, WM-301, WM-449, WM-74, WM-261, WM-467, WM-237, WM-262, WM-295, WM-288, WM-384, and WM-37.

79. The method according to claim 78, wherein the protein is selected from the group consisting of WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, and WM-447.

80. The method according to claim 78, wherein the protein is selected from the group consisting of WM-276, WM-277, WM-362, WM-257, and WM-363.

81. A kit for distinguishing squamous cell lung carcinoma from small cell lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers WM-276, WM-277, WM-362, WM-257, WM-363, WM-347, WM-53, WM-254, WM-17, WM-252, WM-431, WM-513, WM-446, WM-355, WM-447, WM-133, WM-245, WM-52, WM-96, WM-238, WM-243, WM-138, WM-62, WM-580, WM-134, WM-240, WM-256, WM-203, WM-111, WM-95, WM-247, WM-157, WM-242, WM-556, WM-63, WM-239, WM-234, WM-274, WM-370, WM-301, WM-449, WM-74, WM-261, WM-467, WM-237, WM-262, WM-295, WM-288, WM-384, and WM-37, and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

82. A kit according to claim 81, further comprising a washing solution or instructions for making a washing solution.

83. A kit according to claim 81, wherein the substrate is a SELDI probe that comprises functionalities that allow for cation exchange.

84. Software for qualifying lung carcinoma status in a subject, comprising an algorithm for analyzing data extracted from a spectrum generated by mass spectroscopic analysis of a biological sample taken from the subject, wherein said data relates to one or more biomarkers selected from either a first group consisting of

(i) IM-522, IM-273, IN-520, IM-519, IM-454, IM-507, IM-521, IM-148, IM-266, IM-537, IM-471, IM-510, IM-544, IM-474, IM-155, IM-157, IM-176, IM-445, IM-177, IM-440, DA-468, IM-438, IM-547, IM-359, IM-436, IM-106, IM-455, IM-444, IM-158, IM-265, IM-50, IM-159, IM-156, IM-439, IM-157, IM-508, IM-514, IM-478, IM-473, IM-360, IM-435, IM-150, IM-151, IM-110, IM-51, IM-163, IM-437, IM-546, IM-153, and IM-268,

or from a second group consisting of

(ii) WM-61, WM-447, WM-446, WM-133, WM-119, WM-278, WM-134, WM-363, WM-282, WM-362, WM-120, WM-290, WM-65, WM-277, WM-70, WM-369, WM-17, WM-473, WM-47, WM-203, WM-276, WM-279, WM-62, WM-366, WM-456, WM-428, WM-384, WM-287, WM-420, WM-292, WM-431, WM-455, WM-20, WM-340, WM-105, WM-389, WM-63, WM-354, WM-450, WM-466, WM-296, WM-343, WM-341, WM-339, WM-55, WM-66, WM-48, WM-38, WM-138, and WM-310.

85. Software according to claim 84, wherein said algorithm carries out a pattern-recognition analysis that is keyed to data relating to at least one of the biomarkers.

86. Software according to claim 85, wherein said algorithm comprises classification tree analysis that is keyed to data relating to at least one of the biomarkers.

87. Software according to claim 85, wherein said algorithm comprises artificial neural network analysis that is keyed to data relating to at least one of the biomarkers.

88. A method for qualifying lung carcinoma status in a subject, comprised of analyzing a biological sample from said subject for a diagnostic level of a biomarker that is serum amyloid A protein or a fragment thereof.

89. A method according to claim 88, wherein said serum biomarker has an apparent molecular weight of about 2803, 3168, 3277, 3552, 3897, 4300, 4490, 4655, 5927, 6874, 7776, 7941, 8152, 8952, 9233, 10300, 10866, or 10851 Daltons.

90. A method according to claim 89, wherein said serum biomarker has an apparent molecular weight of about 3168, 3277, 3552, 3897, 4300, 4490, 4655, 7776, 7941, 8152, 8952, or 10851 Daltons.

91. A method according to claim 88, wherein said serum biomarker has an apparent molecular weight of about 11.5 to 11.7 kD.

92. A method according to claim 88, for qualifying risk of lung adenocarcinoma.

93. A method according to claim 88, for qualifying risk of squamous cell lung carcinoma.

94. A method according to claim 88, for qualifying risk of small cell lung carcinoma.

95. A method according to claim 88, for qualifying risk of non-small cell lung carcinoma.

96. A method according to claim 88, for qualifying risk of large cell lung carcinoma.

97. A kit for detecting and diagnosing lung carcinoma, comprising

(A) an adsorbent attached to a substrate that retains one or more of the biomarkers that are serum amyloid A protein or a fragment thereof. and

(B) instructions to detect the biomarker(s) by contacting a sample with the adsorbent and detecting the biomarker(s) retained by the adsorbent.

98. A kit according to claim 97, wherein said serum biomarker has an apparent molecular weight of about 2803, 3168, 3277, 3552, 3897, 4300, 4490, 4655, 5927, 6874, 7776, 7941, 8152, 8952, 9233, 10300, 10866, or 10851 Daltons.

99. A kit according to claim 98, wherein said serum biomarker has an apparent molecular weight of about 3168, 3277, 3552, 3897, 4300, 4490, 4655, 7776, 7941, 8152, 8952, or 10851 Daltons.

100. A kit according to claim 97, wherein said serum biomarker has an apparent molecular weight of about 11.5 to 11.7 kD.

101. A kit according to claim 97, further comprising a washing solution or instructions for making a washing solution.

102. A kit according to claim 97, wherein the substrate is a SELDI probe.