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-8198024-B2
Publication Date
2012-06-12
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 a method of predicting clinical outcome without treatment with chemotherapy for a human subject diagnosed with colorectal cancer following surgical resection. The method determines a normalized expression level of an RNA transcript of EFNB2, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject, and uses the normalized EFNB2 expression level to predict the likelihood of a positive clinical outcome without chemotherapy.
The normalized EFNB2 expression level is negatively correlated with an increased likelihood of a positive clinical outcome without treatment with chemotherapy. For subjects diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer, the normalized expression level is positively correlated with an increased likelihood of recurrence of colorectal cancer without treatment with chemotherapy.
The disclosure further describes associations with clinical outcome measures including recurrence-free interval (RFI), overall survival (OS), disease-free survival (DFS), and distant recurrence-free interval (DRFI). It also describes detecting non-linear expression–RFI relationships using a 2 degree-of-freedom natural spline and identifying genes whose association with RFI depends on tumor stage through an interaction model.
Claims Coverage
The independent claims cover two inventive features: predicting a positive clinical outcome without chemotherapy based on normalized EFNB2 RNA transcript expression after surgical resection, and predicting likelihood of recurrence without chemotherapy for Dukes B/C patients based on directionally correlated normalized EFNB2 RNA transcript expression after surgical resection.
Predicting positive clinical outcome without chemotherapy based on normalized EFNB2 expression
Determining a normalized expression level of an RNA transcript of EFNB2, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject after surgical resection, and predicting the likelihood of a positive clinical outcome without treatment with chemotherapy based on the normalized expression level, wherein the normalized expression level is negatively correlated with an increased likelihood of a positive clinical outcome without treatment with chemotherapy.
Predicting recurrence without chemotherapy in Dukes B or Dukes C based on normalized EFNB2 expression
Determining the normalized expression level of an RNA transcript of EFNB2, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject after surgical resection for Dukes B (stage II) or Dukes C (stage III) colorectal cancer, and predicting the likelihood of recurrence of colorectal cancer without treatment with chemotherapy based on the normalized expression level, wherein the normalized expression level is positively correlated with an increased likelihood of recurrence of colorectal cancer without treatment with chemotherapy.
Across the independent claims, the inventive coverage centers on using normalized EFNB2 RNA transcript expression measured from cancer-cell biological samples after surgical resection to predict either positive clinical outcome without chemotherapy or likelihood of recurrence without chemotherapy in Dukes B/C.
Stated Advantages
Provides a method of predicting clinical outcome without treatment with chemotherapy based on normalized EFNB2 RNA transcript expression.
Provides a method of predicting likelihood of recurrence without treatment with chemotherapy in Dukes B (stage II) or Dukes C (stage III) colorectal cancer based on normalized EFNB2 RNA transcript expression.
Documented Applications
Predicting clinical outcome without treatment with chemotherapy after surgical resection in a human subject diagnosed with colorectal cancer.
Predicting likelihood of recurrence of colorectal cancer without treatment with chemotherapy after surgical resection in a human subject diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer.
Interested in licensing this patent?