Method for selecting a treatment for non-small cell lung cancer using gene expression profiles

• US 8,722,331 B2
• Filed: 03/27/2003
• Issued: 05/13/2014
• Est. Priority Date: 03/28/2002
• Status: Active Grant

• Current Assignee: University of Toledo
• Original Assignee: University of Toledo
• Inventors: Demuth, Jeffrey P., Crawford, Erin L., Willey, James C., Weaver, David A., Warner, Kristy A., Graves, Timothy G.
• Primary Examiner(s): MYERS, CARLA J
• Application Number:
  US10/508,932
• Publication Number:
  US 20050260586A1
• Time in Patent Office: 4,065 Days
• US Class Current: 435/6.11
• CPC Class Codes: C12Q 1/6851 Quantitative amplification
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2545/107 with a competitive internal standard/control
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The present invention identifies and quantifies changes in gene expression associated with non-small cell lung cancer NSCLC by examining gene expression in tissue from normal lung and diseased lung. The present invention also identifies and quantifies expression profiles which serve as useful diagnostic markers as well as markers that are useful to monitor disease states, disease progression, drug toxicity, drug efficacy and drug metabolism.

Claims

1. A method for selecting a treatment for non-small cell carcinoma (NSCLC), the method comprising the steps of:

a) providing a sample of NSCLC cells from an individual;

b) determining the levels of mRNA of each of ERCC2, XPC, ABCC5, GTF2H2, XPA and XRCC1 in the sample of NSCLC cells, wherein the levels are determined by quantitative RT-PCR;

c) calculating ratios of ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 using the levels determined in step b);

d) comparing the ratios of step c) to that of ratios of ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 in control NSCLC cells that are cisplatin-resistant, wherein comparing the ratios of step c) to those in control NSCLC cells comprises determining an R² value for each ratio;

e) identifying the sample of NSCLC cells as being cisplatin-resistant based on the comparison of the ratios in step d), wherein the sample of NSCLC cells are identified as being cisplatin resistant when the R² value determined in step d) for each ratio is about 0.87 or greater; and

f) selecting a treatment for NSCLC, wherein treatment not involving cisplatin is selected when the sample of NSCLC cells are identified as being cisplatin resistant in step e) and treatment involving cisplatin is selected when the R² value determined in step d) for any ratio is less than 0.87.

3. The method of claim 1, wherein step a) includes:

obtaining mRNA from the sample, wherein the mRNA comprises ERCC2, XPC, ABCC5, GTF2H2, XPA and XRCC2 mRNA.

4. The method of claim 3, wherein the sample is taken from the individual before cisplatin chemotherapy is administered to the individual.

2. A method of treating an NSCLC cancer patient, the method comprising:

a) obtaining two or more samples comprising NSCLC cancer cells from the NSCLC cancer patient during a course of treatment with cisplatin;

b) for each sample, assaying the sample of NSCLC cells to determine the levels of mRNA of each of ERCC2, XPC, ABCC5, GTF2H2, XPA and XRCC1, wherein the levels are determined by quantitative RT-PCR;

c) for each sample, calculating ratios of ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 using the levels determined in step b);

d) for each sample, comparing the ratios of step c) from the sample of NSCLC cells to ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 ratios of control NSCLC cells that are cisplatin-resistant, wherein comparing the ratios of step c) to those in control NSCLC cells comprises determining an R² value for each ratio;

e) for each sample, identifying the sample of NSCLC cells as being cisplatin-sensitive based on the comparison of the ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 ratios of each sample to the ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 ratios of the control NSCLC cisplatin-resistant cells, wherein the sample of NSCLC cells are identified as being cisplatin sensitive when the R² value determined in step d) for any ratio in a sample is less than 0.87; and

f) continuing cisplatin treatment for the NSCLC cancer patient when the NSCLC cells of the samples maintain cisplatin sensitivity as identified by in step e) during the course of cisplatin treatment.

5. A method to assess response to cisplatin treatment of non-small cell carcinoma (NSCLC) in a human subject having NSCLC comprising:

a) determining the levels of mRNA of each of ERCC2, XPC, ABCC5, GTF2H2, XPA and XRCC1 in a sample of NSCLC cells from the subject before a cisplatin treatment is administered to the subject, wherein the levels of mRNA are determined by quantitative RT-PCR;

b) calculating ratios of ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 for the sample of NSCLC cells from the subject before a cisplatin treatment is administered to the subject using the levels determined in step a);

c) determining the levels of mRNA of each of ERCC2, XPC, ABCC5, GTF2H2, XPA and XRCC1 in a sample of NSCLC cells from the subject after a cisplatin treatment has been administered to the subject, wherein the levels of mRNA are determined by quantitative RT-PCR;

d) calculating ratios of ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 for the sample of NSCLC cells from the subject after a cisplatin treatment has been administered to the subject using the levels determined in step c);

e) for each sample, comparing the calculated ratios for each sample to ABCC5/GTF2H2, XPA/XPC, XRCC1/XPC, ERCC2/XPC and ERCC2/GTF2H2 ratios of control NSCLC cells that are cisplatin-resistant, wherein comparing the calculated ratios for each sample to those in NSCLC cells comprises determining an R² value for each ratio; and

f) predicting that the subject will respond to the cisplatin treatment when the R² values determined in step e) are less than about 0.87 in the sample of NSCLC cells from the subject before a cisplatin treatment is administered to the subject and the sample of NSCLC cells from the subject after a cisplatin treatment has been administered to the subject.