Lung cancer prognostics

• US 20060252057A1
• Filed: 11/30/2005
• Published: 11/09/2006
• Est. Priority Date: 11/30/2004
• Status: Abandoned Application

• Current Assignee: Veridex LLC (Johnson & Johnson)
• Original Assignee: Veridex LLC (Johnson & Johnson)
• Inventors: Raponi, Mitch, Yu, Jack X.
• Application Number:
  US11/290,215
• Publication Number:
  US 20060252057A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/154 Methylation markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: G16B 40/30 Unsupervised data analysis

Abstract

A method of providing a prognosis of lung cancer is conducted by analyzing the expression-of a group of genes. Gene expression profiles in a variety of medium such as microarrays are included as are kits that contain them.

Claims

2. A method of staging lung cancer patients comprising the steps of

a. obtaining a biological sample from a lung cancer patient;

and

b. measuring Biomarkers associated with Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7

wherein the expression levels of the Marker genes above or below pre-determined cut-off levels are indicative of the lung cancer stage.

3. The method of claim 2 wherein the stage corresponds to classification by the TNM system.

4. The method of claim 2 wherein the stage corresponds to patients with similar gene expression profiles.

5. A method of determining lung cancer patient treatment protocol comprising the steps of

a. obtaining a biological sample from a lung cancer patient;

and

b. measuring Biomarkers associated with Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7

wherein the expression levels of the Marker genes above or below pre-determined cut-off levels are sufficiently indicative of risk of recurrence to enable a physician to determine the degree and type of therapy recommended to prevent recurrence.

6. A method of treating a lung cancer patient comprising the steps of:

a. obtaining a biological sample from a lung cancer patient; and

b. measuring Biomarkers associated with Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7

wherein the expression levels of the Marker genes above or below pre-determined cut-off levels are indicate a high risk of recurrence and;

c. treating the patient with adjuvant therapy if they are a high risk patient.

7. A method of determining whether a lung cancer patient is high or low risk of mortality comprising the steps of

a. obtaining a biological sample from a lung cancer patient;

and

b. measuring Biomarkers associated with Marker genes corresponding to those selected from Table 4

wherein the expression levels of the Marker genes above or below pre-determined cut-off levels are sufficiently indicative of risk of mortality to enable a physician to determine the degree and type of therapy recommended.

18-1. The method of claim 1, 2, 5, 6 or 7 wherein gene expression is determined by nucleic acid amplification conducted by polymerase chain reaction (PCR) of RNA extracted from the sample.

29. A composition comprising at least one probe set selected from the group consisting of:

Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7.

30. A kit for conducting an assay to determine lung cancer prognosis in a biological sample comprising:

materials for detecting isolated nucleic acid sequences, their complements, or portions thereof of a combination of genes selected from the group consisting of Marker genes corresponding to those selected from Table I, Table 4, Table 5 or Table 7.

31. The kit of claim 30 further comprising reagents for conducting a microarray analysis.

32. The kit of claim 30 further comprising a medium through which said nucleic acid sequences, their complements, or portions thereof are assayed.

33. Articles for assessing lung cancer status comprising:

materials for detecting isolated nucleic acid sequences, their complements, or portions thereof of a combination of genes selected from the group consisting of Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7.

34. The articles of claim 33 further comprising reagents for conducting a microarray analysis.

35. The articles of claim 34 further comprising a medium through which said nucleic acid sequences, their complements, or portions thereof are assayed.

43. A diagnostic/prognostic portfolio comprising isolated nucleic acid sequences, their complements, or portions thereof of a combination of genes selected from the group consisting of Marker genes corresponding to those selected from Table 1, Table 4, Table 5 or Table 7.

44. The portfolio of claim 43 wherein the measurement or characterization is at least 1.5-fold over- or under-expression.

45. The portfolio of claim 44 wherein the measurement provides a statistically significant p-value over- or under-expression.

46. The portfolio of claim 44 wherein the p-value is less than 0.05.