PROGNOSTIC AND PREDICTIVE GENE SIGNATURE FOR NON-SMALL CELL LUNG CANCER AND ADJUVANT CHEMOTHERAPY
The application provides methods of prognosing and classifying lung cancer patients into poor survival groups or good survival groups and for determining the benefit of adjuvant chemotherapy by way of a multigene signature. The application also includes kits and computer products for use in the methods of the application.
1 - 44 . (canceled)
45 . A method for prognosing or classifying a subject with non-small cell lung cancer (NSCLC) comprising:
determining relative expression levels of at least 15 biomarkers in a tumor sample from the subject, wherein the at least 15 biomarkers comprise FAM64A, MB, EDN3, ZNF236, FOSL2, MYT1L, MLANA, L1CAM, TRIM14, STMN2, UMPS, ATP1B1, HEXIM1, IKBKAP, and MDM2;
calculating a combined score from the relative expression levels, including the relative expression levels of FAM64A, MB, EDN3, ZNF236, FOSL2, MYT1L, MLANA, L1CAM, TRIM14, STMN2, UMPS, ATP1B1, HEXIM1, IKBKAP, and MDM2, and classifying the subject into a high or low risk group based on the combined score.
46 . The method of claim 45 , further comprising selecting adjuvant chemotherapy if the subject is in the high risk group.
47 . The method of claim 45 , further comprising selecting resection alone for the low risk group.
48 . The method of claim 45 , wherein the combined score is calculated from the relative expression levels of 16, 17, or 18 biomarkers.
49 . The method of claim 48 , wherein the one, two or three additional biomarkers are selected from Table 3.
50 . The method of claim 45 , wherein the additional one, two, or three biomarkers are selected from RGS4, UGT2B4, and MCF2.
51 . The method of claim 45 , wherein the combined score is calculated according to Formula I:
Combined score=0.557 ×PC 1+0.328 ×PC 2+0.43 ×PC 3+0.335 ×PC 4 (Formula I),
wherein PC1 is the sum of the relative expression level for each biomarker multiplied by a first principal component for each biomarker, PC2 is the sum of the relative expression level for each biomarker multiplied by a second principal component for each biomarker, PC3 is the sum of the relative expression level for each biomarker multiplied by a third principal component for each biomarker, and PC4 is the sum of the relative expression level of each biomarker multiplied by a fourth principal component for each biomarker.
52 . The method of claim 45 , and wherein the subject has stage I or stage II NSCLC.
53 . The method of claim 45 , wherein the relative expression levels are determined by microarray.
54 . The method of claim 45 , wherein the relative expression levels are determined by quantitative PCR.
55 . A method for prognosing or classifying a subject with stage I or stage II non-small cell lung cancer (NSCLC) comprising:
determining relative expression levels of at least 15 biomarkers in a tumor sample from the subject, wherein the at least 15 biomarkers comprise FAM64A, MB, EDN3, ZNF236, FOSL2, MYT1L, MLANA, L1CAM, TRIM14, STMN2, UMPS, ATP1B1, HEXIM1, IKBKAP, and MDM2;
calculating a combined score from the relative expression levels, including the relative expression levels of FAM64A, MB, EDN3, ZNF236, FOSL2, MYT1L, MLANA, L1CAM, TRIM14, STMN2, UMPS, ATP1B1, HEXIM1, IKBKAP, and MDM2, and
classifying the subject into a high or low risk group based on the combined score, and
selecting adjuvant chemotherapy if the subject is in the high risk group, and selecting resection alone for the low risk group.
56 . The method of claim 55 , wherein the combined score is calculated from the relative expression levels of 16, 17, or 18 biomarkers.
57 . The method of claim 56 , wherein the one, two or three additional biomarkers are selected from Table 3.
58 . The method of claim 57 , wherein the additional one, two, or three biomarkers are selected from RGS4, UGT2B4, and MCF2.
59 . The method of claim 55 , wherein the combined score is calculated according to Formula I:
Combined score=0.557 ×PC 1+0.328 'PC 2+0.43 ×PC 3+0.335 ×PC 4 (Formula I),
wherein PC1 is the sum of the relative expression level for each biomarker multiplied by a first principal component for each biomarker, PC2 is the sum of the relative expression level for each biomarker multiplied by a second principal component for each biomarker, PC3 is the sum of the relative expression level for each biomarker multiplied by a third principal component for each biomarker, and PC4 is the sum of the relative expression level of each biomarker multiplied by a fourth principal component for each biomarker.
60 . The method of claim 55 , wherein the relative expression levels are determined by microarray.
61 . The method of claim 55 , wherein the relative expression levels are determined by quantitative PCR.