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Publication Number
US-9976188-B2
Publication Date
2018-05-22
Expiration Date
Abstract
Biomarkers and methods using the biomarkers for the prediction of the recurrence risk of cancer in a patient are provided.
Core Innovation
The invention relates to using cell-cycle genes, including TPX2, for cancer biomarker analysis in prostate cancer tumor tissue. A sample comprising prostate cancer tumor tissue is obtained from a patient, and the expression of a panel of genes comprising TPX2 is determined by quantitative PCR of cDNA.
The measured TPX2 expression is used to prognose the likelihood of prostate cancer progression by comparing the expression level to a threshold index value. The invention distinguishes prognoses based on whether TPX2 expression is lower than the threshold index value or exceeds the threshold index value, thereby enabling different patient prognostic classifications.
The invention supports normalization using housekeeping genes for the quantitative PCR-based expression determination. In particular, housekeeping genes are determined and TPX2 expression is normalized to the expression of housekeeping genes, with CLTC identified as a specific housekeeping gene.
The invention further links the prognosis to clinical management decisions, including administering active surveillance when prognosis indicates a decreased likelihood of progression and administering one or more of chemotherapy, radiation therapy, or surgery when prognosis indicates an increased likelihood of progression. A computer system is described for analyzing marker data and generating recurrence likelihood outputs, and empirical validation is reported for a CCG signature and additive predictive value of PTEN status.
Claims Coverage
The partial content contains two independent claims (clm-00001 and clm-00005). Across these independent claims, the inventive concept centers on quantitative PCR of cDNA expression of a TPX2-containing gene panel in prostate cancer tumor tissue, prognosis based on a threshold index value, and treatment selection; dependent claims additionally require normalization using housekeeping genes and can include CLTC.
Quantitative PCR of cDNA expression of a TPX2-containing gene panel for active surveillance decision
Prognosing a patient as having a decreased likelihood of prostate cancer progression when the expression of the gene TPX2 is lower than a threshold index value, and administering active surveillance based on the prognosis after determining by quantitative PCR of cDNA the expression of a panel of genes comprising TPX2 in prostate cancer tumor tissue.
Quantitative PCR of cDNA expression of a TPX2-containing gene panel for progression treatment selection
Prognosing a patient as having an increased likelihood of prostate cancer progression when the expression of the gene TPX2 exceeds a threshold index value, and administering one or more of chemotherapy, radiation therapy or surgery based on the prognosis after determining by quantitative PCR of cDNA the expression of a panel of genes comprising TPX2 in prostate cancer tumor tissue.
Normalization of TPX2 quantitative PCR expression using housekeeping genes including CLTC
Determining the expression of one or more housekeeping genes and normalizing TPX2 gene expression to the expression of the housekeeping genes, wherein the housekeeping genes include the gene CLTC.
Taken together, the independent claims require TPX2-containing gene-panel expression measurement by quantitative PCR of cDNA from prostate cancer tumor tissue, prognosis based on whether TPX2 expression is below or above a threshold index value, and corresponding administration of active surveillance or one or more of chemotherapy, radiation therapy, or surgery; dependent claims further specify normalization using housekeeping genes with CLTC included.
Stated Advantages
Prognosis provides a basis to administer active surveillance when the likelihood of prostate cancer progression is decreased based on TPX2 expression relative to a threshold index value.
Prognosis provides a basis to administer one or more of chemotherapy, radiation therapy, and/or surgery when the likelihood of prostate cancer progression is increased based on TPX2 expression relative to a threshold index value.
Empirical validation is reported showing prognostic improvement of a 31-CCG prostate signature over clinical nomograms, and additive predictive value of PTEN mutations/status.
Documented Applications
Clinical decision support for prostate cancer management, including administering active surveillance or administering one or more of chemotherapy, radiation therapy or surgery based on prognosis derived from quantitative PCR of cDNA expression of TPX2 within a gene panel.
Recurrence likelihood output generation using marker data analyzed by a computer system.
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