BACKGROUND: The kallikrein-related peptidases (KLKs) have been implicated in many types of cancer, including prostate and ovarian. MATERIALS AND METHODS: We performed a comprehensive in silico study to characterize the KLK locus using transcriptomic (gene expression) and genomic (mutations and DNA copy number) data in prostate cancer (n=194), serous ovarian cancer (n=506), glioblastoma multiforme (n=206), and sarcoma (n=207) from The Cancer Genome Atlas and independent publicly available datasets to assess KLKs as cancer biomarkers. RESULTS: Overall, there was mRNA overexpression in prostate and serous ovarian cancer and decreased expression in glioblastoma multiforme. There was higher frequency of genomic loss in serous ovarian cancer, and rare KLK gene mutations observed in serous ovarian cancer and GBM. Dysregulation of KLKs correlates with survival: for prostate cancer, a combination of dysregulation of KLK1, 5 and 13 was associated with worse disease-free survival. CONCLUSION: We conclude that specific dysregulation of KLKs at the genetic and transcriptomic levels have useful prognostic value.
BACKGROUND: The kallikrein-related peptidases (KLKs) have been implicated in many types of cancer, including prostate and ovarian. MATERIALS AND METHODS: We performed a comprehensive in silico study to characterize the KLK locus using transcriptomic (gene expression) and genomic (mutations and DNA copy number) data in prostate cancer (n=194), serous ovarian cancer (n=506), glioblastoma multiforme (n=206), and sarcoma (n=207) from The Cancer Genome Atlas and independent publicly available datasets to assess KLKs as cancer biomarkers. RESULTS: Overall, there was mRNA overexpression in prostate and serous ovarian cancer and decreased expression in glioblastoma multiforme. There was higher frequency of genomic loss in serous ovarian cancer, and rare KLK gene mutations observed in serous ovarian cancer and GBM. Dysregulation of KLKs correlates with survival: for prostate cancer, a combination of dysregulation of KLK1, 5 and 13 was associated with worse disease-free survival. CONCLUSION: We conclude that specific dysregulation of KLKs at the genetic and transcriptomic levels have useful prognostic value.
Authors: Ruli Gao; Shanshan Bai; Ying C Henderson; Yiyun Lin; Aislyn Schalck; Yun Yan; Tapsi Kumar; Min Hu; Emi Sei; Alexander Davis; Fang Wang; Simona F Shaitelman; Jennifer Rui Wang; Ken Chen; Stacy Moulder; Stephen Y Lai; Nicholas E Navin Journal: Nat Biotechnol Date: 2021-01-18 Impact factor: 54.908