Gene expression markers for colorectal cancer prognosis
Inventors
Watson, Drew • Paik, Soonmyung • Cowens, Wayne • Baker, Joffre B. • Clark, Kim • Hackett, James
Assignees
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Publication Number
US-8153379-B2
Publication Date
2012-04-10
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 described invention concerns predicting clinical outcomes in a human subject diagnosed with Dukes B (Stage II) or Dukes C (Stage III) colorectal cancer following surgical resection. The method determines a normalized expression level of an RNA transcript of BGN, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject, and compares the normalized BGN expression level to gene expression data obtained from colorectal cancer reference samples comprising cancer cells derived from patients with colorectal cancer.
In the Dukes B/Stage II or Dukes C/Stage III context, predicting a positive clinical outcome is based on a correlation relationship in which the normalized expression level of the BGN RNA transcript, or expression product, is negatively correlated with an increased likelihood of a positive clinical outcome. The clinical outcome includes one or more survival and recurrence interval measures including Recurrence-Free Interval (RFI), Overall Survival (OS), Disease-Free Survival (DFS), and Distant Recurrence-Free Interval (DRFI).
The described invention also covers predicting recurrence of colorectal cancer after surgical resection in the same Dukes B (Stage II) or Dukes C (Stage III) patient group. In that recurrence prediction method, the normalized BGN RNA transcript, or expression product, is positively correlated with an increased likelihood of recurrence, and the comparison is made to gene expression data from colorectal cancer reference samples comprising cancer cells derived from patients.
Claims Coverage
Two independent claims are present. Both use normalized BGN RNA transcript, or expression product, expression in biological samples comprising cancer cells from Dukes B (Stage II) and Dukes C (Stage III) colorectal cancer subjects, compared with colorectal cancer reference gene expression data.
Predicting positive clinical outcome using negatively correlated BGN expression versus reference data
Determining a normalized expression level of an RNA transcript of BGN, or an expression product thereof, in a biological sample comprising cancer cells from the human subject diagnosed with Dukes B (Stage II) or Dukes C (Stage III) colorectal cancer, and predicting the likelihood of a positive clinical outcome by comparing the normalized BGN expression level to gene expression data from colorectal cancer reference samples comprising cancer cells derived from patients with colorectal cancer, wherein the normalized BGN expression level is negatively correlated with an increased likelihood of a positive clinical outcome.
Predicting recurrence using positively correlated BGN expression versus reference data
Determining a normalized expression level of an RNA transcript of BGN, or an expression product thereof, in a biological sample comprising cancer cells from the human subject diagnosed with Dukes B (Stage II) or Dukes C (Stage III) colorectal cancer, and predicting the likelihood of recurrence of colorectal cancer by comparing the normalized BGN expression level to gene expression data from colorectal cancer reference samples comprising cancer cells derived from patients with colorectal cancer, wherein the normalized BGN expression level is positively correlated with an increased likelihood of recurrence of colorectal cancer.
The claims center on normalized BGN RNA transcript, or expression product, expression in cancer-cell biological samples from Dukes B (Stage II) and Dukes C (Stage III) colorectal cancer patients, using comparison to colorectal cancer reference gene-expression data. The independent claims differ by whether BGN expression is negatively correlated with positive clinical outcome or positively correlated with recurrence likelihood.
Stated Advantages
Enables prediction of clinical outcome following surgical resection in Dukes B (Stage II) and Dukes C (Stage III) colorectal cancer based on normalized BGN RNA transcript expression compared to reference sample gene expression data.
Enables prediction of likelihood of recurrence of colorectal cancer after surgical resection in Dukes B (Stage II) and Dukes C (Stage III) based on normalized BGN RNA transcript expression compared to reference sample gene expression data.
Allows expression of the clinical outcome in terms of survival and recurrence interval measures including RFI, OS, DFS, and DRFI.
Supports refinement of prediction using additional RNA transcript markers with specified correlation directions.
Documented Applications
Predicting a positive clinical outcome following surgical resection in a human subject diagnosed with Dukes B (Stage II) or Dukes C (Stage III) colorectal cancer using normalized BGN RNA transcript expression compared to reference sample gene expression data.
Predicting a likelihood of recurrence of colorectal cancer following surgical resection in a human subject diagnosed with Dukes B (Stage II) or Dukes C (Stage III) colorectal cancer using normalized BGN RNA transcript expression compared to reference sample gene expression data.
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