Gene expression markers for colorectal cancer prognosis
Inventors
Watson, Drew • Paik, Soonmyung • Cowens, Wayne • Baker, Joffre B. • Clark, Kim • Hackett, James
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8273537-B2
Publication Date
2012-09-25
Expiration Date
Abstract
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.
Core Innovation
The invention relates to predicting clinical outcome and recurrence for a human subject diagnosed with colorectal cancer following surgical resection. It determines normalized expression levels of RNA transcripts of CMYC and Ki-67, or expression products thereof, in a biological sample comprising cancer cells obtained from the human subject. The likelihood of a positive clinical outcome or recurrence is predicted based on the relationship between the normalized expression levels and the clinical outcome.
In one aspect, the normalized expression levels of RNA transcripts of CMYC and Ki-67, or expression products thereof, are positively correlated with an increased likelihood of a positive clinical outcome. In another aspect for Dukes B (stage II) or Dukes C (stage III) colorectal cancer, the normalized expression levels of RNA transcripts of CMYC and Ki-67, or expression products thereof, are negatively correlated with an increased likelihood of recurrence of colorectal cancer after surgical resection.
The disclosed approach is grounded in gene-expression association with colorectal cancer clinical outcomes, including multivariate Cox proportional hazards analyses for recurrence-free interval (RFI) with controlling clinical/demographic covariates, tests of nonlinearity using a natural spline (2 df), and interaction tests between gene expression and tumor stage. Follow-on results are described using a second analysis study with a specified reference gene set, and the document provides extensive gene-level findings including hazard ratios (HR) and p-values for multiple named genes.
Claims Coverage
The document includes two independent methods. Across these independent claims, the coverage centers on predicting an outcome or recurrence likelihood using normalized expression levels of CMYC and Ki-67 (or expression products) measured in a cancer-cell biological sample after colorectal cancer surgical resection, with opposite correlation directions for positive clinical outcome versus recurrence in Dukes B/C disease.
Positive correlation outcome prediction from CMYC and Ki-67 expression
A method predicting clinical outcome for a human subject with colorectal cancer following surgical resection by determining normalized expression levels of RNA transcripts of CMYC and Ki-67, or expression products thereof, in a biological sample comprising cancer cells from the human subject; predicting a likelihood of a positive clinical outcome based on the normalized expression levels, wherein the normalized expression levels are positively correlated with an increased likelihood of a positive clinical outcome.
Negative correlation recurrence prediction in Dukes B/C from CMYC and Ki-67 expression
A method predicting a likelihood of recurrence of colorectal cancer in a human subject diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer following surgical resection by determining normalized expression levels of RNA transcripts of CMYC and Ki-67, or expression products thereof, in a biological sample comprising cancer cells from the human subject; predicting the likelihood of recurrence based on the normalized expression levels, wherein the normalized expression levels are negatively correlated with an increased likelihood of recurrence.
Both independent claims require normalized CMYC and Ki-67 (or expression products) expression measurement in a cancer-cell biological sample and use the correlation direction of those normalized expression levels with the likelihood of a clinical endpoint, whether positive outcome or recurrence in Dukes B/C.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?