Method of diagnosing, treating and determining progression and survival of cancer cells using BCL-2 antagonist of cell death (BAD) pathway gene signature
The present invention relates to the BAD pathway's influence on development, progression, chemo-sensitivity, and overall survival for multiple human cancers and its potential as a therapeutic target to increase chemo-sensitivity. BAD pathway expression was associated with the development and/or progression of breast, colon, and endometrial cancers, relapse-free survival from breast cancer, and overall survival from ovarian, colon, and brain cancers. Expression was also associated with in vitro sensitivity to a range of cytotoxic agents. pBAD levels were higher in cancer versus immortalized normal cells and chemo-resistant versus—sensitive cancer cells and associated with increased cell proliferation.
1. A method of treating ovarian cancer comprising:
obtaining a sample suspected of being cancerous or pre-cancerous from a patient;
obtaining an expression level of BAD pathway genes EGFR, SOS2, IGF1R, BAD, PRKAR1A, and YWHAZ;
determining a BAD Pathway Gene Expression Signature (BPGES) score of the sample wherein the BPGES score is determined by principal component analysis (PCA) in which X=t 1 *p 1 ′+t 2 *p 2 ′+t 3 *p 3 ′+ . . . +t A *p A ′+E, where X is gene expression value, t i is score, p i is loading coefficient, and E is residual matrix;
calculating a median BPGES score using a highest and a lowest value of the expression levels of the BAD pathway genes obtained in the sample;
determining if the cancerous or pre-cancerous cells of the patient will be sensitive to carboplatin by comparing the BAD Pathway Gene Expression Signature (BPGES) score of the sample suspected of being cancerous or pre-cancerous to the median BPGES score;
wherein a high BAD Pathway Gene Expression Signature (BPGES) score as compared to the median BPGES score is indicative of chemosensitive ovarian cancer; and
administering carboplatin to the patient having the high BPGES score.