Gene expression markers for colorectal cancer prognosis
Inventors
Cowens, Wayne • Baker, Joffre B. • Clark-Langane, Kim • Hackett, James • Watson, Drew • Paik, Soonmyung
Assignees
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Publication Number
US-8367345-B2
Publication Date
2013-02-05
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 for a human subject diagnosed with colorectal cancer following surgical resection. The method determines a normalized expression level of an RNA transcript of LAMA3, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject, and predicts the likelihood of a positive clinical outcome based on the normalized LAMA3 level.
The invention further predicts the likelihood of recurrence of colorectal cancer following surgical resection in a human diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer. In these contexts, the normalized expression level of an RNA transcript of LAMA3, or an expression product thereof, is negatively correlated with an increased likelihood of a positive clinical outcome and positively correlated with an increased likelihood of recurrence.
An additional embodiment uses fixed, paraffin-embedded biological samples comprising cancer cells. RNA is extracted, reverse transcribed to produce cDNA of LAMA3, amplified to produce an amplicon, assayed, normalized against at least one reference RNA transcript level, and compared to gene expression data obtained from at least 30 reference colorectal cancer tissue samples before predicting the likelihood of a positive clinical outcome.
Claims Coverage
The consolidated independent claims cover three inventive features. They focus on using normalized LAMA3 RNA expression or normalized LAMA3 amplicon level from cancer-cell biological samples to predict positive clinical outcome or recurrence likelihood in colorectal cancer after surgical resection, including Dukes B (stage II) and Dukes C (stage III) contexts.
Normalized LAMA3 expression predicts positive clinical outcome after colorectal resection
Determining a normalized expression level of an RNA transcript of LAMA3, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human 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.
Normalized LAMA3 expression predicts recurrence in Dukes B and Dukes C
Determining the normalized expression level of an RNA transcript of LAMA3, or an expression product thereof, in a biological sample comprising cancer cells obtained from the human subject, and predicting the likelihood of recurrence of colorectal cancer based on the normalized expression level, wherein the normalized expression level is positively correlated with an increased likelihood of recurrence, for a human subject diagnosed with Dukes B (stage II) or Dukes C (stage III) colorectal cancer following surgical resection.
Normalized LAMA3 amplicon level compared to reference tissue data predicts positive clinical outcome
Extracting RNA from a fixed, paraffin-embedded biological sample comprising cancer cells; reverse transcribing an RNA transcript of LAMA3 to produce a cDNA of LAMA3; amplifying the cDNA of LAMA3; producing an amplicon of the RNA transcript of LAMA3; assaying a level of the amplicon of the RNA transcript of LAMA3; normalizing the level of the amplicon against a level of an amplicon of at least one reference RNA transcript to provide a normalized LAMA3 amplicon level; comparing the normalized LAMA3 amplicon level to gene expression data obtained from at least 30 reference colorectal cancer tissue samples; and predicting the likelihood of a positive clinical outcome for the human subject based on the normalized LAMA3 amplicon level, wherein the normalized LAMA3 amplicon level is negatively correlated with an increased likelihood of a positive clinical outcome, with the clinical outcome expressed in terms of RFI, OS, DFS, or DRFI.
The independent claims collectively cover LAMA3 RNA expression as a predictive biomarker in colorectal cancer after surgical resection, including prediction of positive clinical outcomes with negative correlation, prediction of recurrence risk in Dukes B and Dukes C with positive correlation, and a normalized amplicon approach with reference tissue dataset comparison supporting outcome prediction across RFI, OS, DFS, and DRFI.
Stated Advantages
Not explicitly described in patent.
Documented Applications
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