Gene expression markers for colorectal cancer prognosis
View Patent ↗A method of predicting clinical outcome in a subject diagnosed with colorectal cancer comprising determining evidence of the expression of one or more predictive RNA transcripts or their expression products in a biological sample of cancer cells obtained from the subject.
1. A method of predicting clinical outcome for a human subject diagnosed with colorectal cancer following surgical resection of said cancer, comprising:
assaying a normalized expression level of an RNA transcript, or an expression product thereof, of INHBA, MYBL2, FAP and Ki67 in a biological sample comprising colorectal cancer cells obtained from the human subject;
determining a likelihood of a positive clinical outcome for the human subject based on the normalized expression, wherein
(a) normalized expression of each of INHBA and FAP is negatively correlated with an increased likelihood of a positive clinical outcome; and
(b) normalized expression of each of MYBL2 and Ki67 is positively correlated with an increased likelihood of a positive clinical outcome; and
providing a report comprising a score, wherein the score is indicative of the likelihood of a positive clinical outcome in the human subject.
2. The method of claim 1 wherein evidence of said normalized expression level is obtained by a method of gene expression profiling.
3. The method of claim 2 wherein said method is a PCR-based method.
4. The method of claim 3 wherein said normalized expression level is normalized relative to the expression level of one or more reference genes, or their expression products.
5. The method of claim 1 wherein said positive clinical outcome is expressed in terms of Recurrence-Free Interval (RFI), Disease-Free Survival (DFS), or Distant Recurrence-Free Interval (DRFI).
6. The method of claim 1 wherein said cancer is Dukes B (stage II) or Dukes C (stage III) colorectal cancer.
7. The method of claim 6 wherein said cancer is Dukes B (stage II) or Dukes C (stage III) colon cancer.
8. The method of claim 1 , wherein said assaying comprises assaying a normalized expression level of an RNA transcript, or an expression product thereof, of one or more of BGN, GADD45B, COL1A1, SPARC, COL1A2, and CYMC in the biological sample, wherein
(a) normalized expression of each of BGN, GADD45B, COL1A1, SPARC, and COL1A2 is negatively correlated with an increased likelihood of a positive clinical outcome; and
(b) normalized expression of CMYC is positively correlated with an increased likelihood of a positive clinical outcome.
9. A method of predicting in a human subject diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer a likelihood of recurrence of colorectal cancer following surgical resection of said cancer, comprising:
assaying a normalized expression level of an RNA transcript, or an expression product thereof, of INHBA, MYBL2, FAP and Ki67 in a biological sample comprising colorectal cancer cells obtained from the human subject, wherein
(a) normalized expression of each of INHBA and FAP is negatively correlated with a decreased likelihood of recurrence of colorectal cancer; and
(b) normalized expression of each of MYBL2 and Ki67 is positively correlated with a decreased likelihood of recurrence of colorectal cancer; and
providing a report comprising a score, wherein the score is indicative of the likelihood of a recurrence of colorectal cancer in the human subject.
10. The method of claim 9 , wherein said assaying comprises assaying a normalized expression level of an RNA transcript, or an expression product thereof, of one or more of BGN, GADD45B, COL1A1, SPARC, COL1A2, and CYMC in the biological sample, wherein
(a) normalized expression of each of BGN, GADD45B, COL1A1, SPARC, and COL1A2 is negatively correlated with a decreased likelihood of recurrence of colorectal cancer; and
(b) normalized expression of CYMC is positively correlated with a decreased likelihood of recurrence of colorectal cancer.
11. The method of claim 9 wherein evidence of said expression level is obtained by a method of gene expression profiling.
12. The method of claim 11 wherein said method is a PCR-based method.
13. The method of claim 9 , wherein, if said likelihood of recurrence is predicted to be increased, said human subject is subjected to further therapy following said surgical removal.
14. The method of claim 13 wherein said further therapy is chemotherapy and/or radiation therapy.
15. The method of claim 9 , wherein said normalized expression level is normalized relative to the expression level of one or more reference genes, or their expression products.
16. The method of claim 9 wherein, said positive clinical outcome is expressed in terms of Recurrence-Free Interval (RFI), Disease-Free Survival (DFS), or Distant Recurrence-Free Interval (DRFI).
17. The method of claim 9 wherein, said colorectal cancer is Dukes B (stage II) or Dukes C (stage III) colorectal cancer.
18. The method of claim 17 wherein said colorectal cancer is Dukes B (stage II) or Dukes C (stage III) colon cancer.