Gene expression markers for prediction of patient response to chemotherapy
View Patent ↗The present invention relates to gene sets useful in assessing prognosis and/or predicting the response of cancer, e.g. colorectal cancer to chemotherapy. In addition, the invention relates to a clinically validated cancer test, e.g. colorectal test, for assessment of prognosis and/or prediction of patient response to chemotherapy, using expression analysis. The present invention accommodates the use of archived paraffin embedded biopsy material for assay of all markers in the relevant gene sets and therefore is compatible with the most widely available type of biopsy material.
1. A method of predicting a likelihood that a human patient diagnosed with colorectal cancer will exhibit a positive clinical response to treatment with chemotherapy, comprising:
determining a level of an RNA transcript of HSPE1, or an expression product thereof, in a tumor sample obtained from said patient,
using the level of the RNA transcript of HSPE1, or an expression product thereof, to calculate a likelihood of a positive clinical response to chemotherapy, wherein
increased level of the RNA transcript of HSPE1, or an expression product thereof, is positively correlated with an increased likelihood of a positive response to chemotherapy.
2. The method of claim 1 wherein said method is a PCR-based method.
3. The method of claim 1 wherein said method is an array-based method.
4. The method of claim 1 , wherein said level is normalized relative to the expression levels of one or more reference genes, or their expression products.
5. The method of claim 1 , wherein the colorectal cancer is Dukes B (stage II) or Dukes C (stage III) colorectal cancer.
6. The method of claim 1 , wherein said colorectal cancer is colon cancer.
7. The method of claim 6 , wherein said colon cancer is Duke B (stage II) or Dukes C (stage III) colon cancer.
8. The method of claim 1 wherein the chemotherapy is a 5-fluorouracil (5-FU) therapy.
9. The method of claim 1 , further comprising determining a level of an RNA transcript, or an expression product thereof, of one or more genes selected from AURKB, Axin 2, BRAF, BRCA2, BUB1, C20orf1, CASP9, CDC2, CENPA, CENPF, CLIC1, CYR61, Cdx2, Chk1, DLC1, DUSP1, E2F1, ESPL1, FBXO5, FGF2, FOS, GSK3B, Grb10, HES6, HNRPAB, HOXB13, KIF22, MSH2, MSH3, NR4A1, PRDX2, RAD54L, RANBP2, ROCK2, RhoB, S100P, SAT, SOD1, STK15, TCF-1, TOP2A, TP53BP1, UBE2C, and VCP, wherein increased level the RNA transcript, or an expression product thereof, of the one or more genes is positively correlated with an increased likelihood of a positive response to chemotherapy.
10. The method of claim 1 , further comprising determining a level of an RNA transcript, or an expression product thereof, of one or more genes selected from ABCB1, AMFR, ANXA1, APC, B-Catenin, CALD1, CD68, CDH11, CHFR, CLTC, COL1A1, COL1A2, CREBBP, CTSB, CTSL, EFNB2, EPAS1, FPGS, FZD1, GPX1, HIF1A, HNRPD, HSD17B2, IGFBP3, IGFBP7, IL6ST, ITGA5, KLF5, LEF, MADH7, MCM3, MCP1, MMP1, MMP2, Maspin, NRP1, PDGFC, PDGFRa, PFN2, PKR2, RUNX1, SEMA4B, SKP2, SPARC, TIMP1, UPP1, and VDAC2, wherein increased level of the RNA transcript, or an expression product thereof, of the one or more genes is negatively correlated with a likelihood of a positive response to chemotherapy.
11. The method of claim 1 , wherein the clinical response is expressed in terms of Recurrence-Free Interval (RFI), Overall Survival (OS), Disease-Free Survival (DFS), or Distant Recurrence-Free Interval (DRFI).
12. The method of claim 1 , further comprising generating a report based on the likelihood of a positive clinical response to chemotherapy.
13. The method of claim 1 , wherein the tumor sample is a fixed, paraffin-embedded, fresh, or frozen tissue sample.