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-8026060-B2
Publication Date
2011-09-27
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 methods of predicting clinical outcome for a human subject diagnosed with colorectal cancer following surgical resection. The methods determine a normalized expression level of an RNA transcript of GADD45B, or an expression product thereof, in a biological sample comprising cancer cells obtained from the subject, and predict the likelihood of a positive clinical outcome based on the normalized GADD45B level.
The invention further extends the same GADD45B normalized-expression framework to predicting the likelihood of recurrence of colorectal cancer in a human subject with Dukes B (stage II) or Dukes C (stage III) colorectal cancer following surgical resection. In this recurrence-focused method, the normalized expression level of an RNA transcript of GADD45B, or an expression product thereof, is positively correlated with an increased likelihood of colorectal cancer recurrence.
The described approaches include additional predictive RNA transcript biomarkers and correlation direction relationships, along with determination and normalization of expression levels. The clinical outcome and/or recurrence likelihood is expressed using Recurrence-Free Interval (RFI), Overall Survival (OS), Disease-Free Survival (DFS), or Distant Recurrence-Free Interval (DRFI).
Claims Coverage
The document includes two independent claims: one predicting likelihood of a positive clinical outcome based on negatively correlated normalized GADD45B expression, and one predicting likelihood of recurrence in Dukes B/C patients based on positively correlated normalized GADD45B expression. Each independent claim centers on determining a normalized expression level of an RNA transcript of GADD45B (or an expression product) from a post-resection cancer-cell biological sample and predicting the applicable clinical outcome or recurrence likelihood from that normalized level.
GADD45B normalized expression predicts positive clinical outcome after resection
A method of predicting clinical outcome for a human subject diagnosed with colorectal cancer following surgical resection, comprising determining a normalized expression level of an RNA transcript of GADD45B, or an expression product thereof, in a biological sample comprising cancer cells obtained from the subject, and predicting the likelihood of a positive clinical outcome based on the normalized expression level, wherein the normalized expression level is negatively correlated with an increased likelihood of a positive clinical outcome.
GADD45B normalized expression predicts recurrence likelihood in Dukes B/C after resection
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, comprising determining the normalized expression level of an RNA transcript of GADD45B, or an expression product thereof, in a biological sample comprising cancer cells obtained from the subject, and predicting the likelihood of recurrence based on the normalized expression level, wherein the normalized expression level is positively correlated with an increased likelihood of recurrence.
Across both independent claims, the inventive core is the determination of a normalized GADD45B (RNA transcript or expression product) level in a post-surgical resection cancer-cell sample and using correlation direction to predict colorectal-cancer clinical outcomes.
Stated Advantages
Documented Applications
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