KLK4 Gene Expression Predicts Colorectal Tumor Recurrence

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(ChemotherapyAdvisor) – Greek researchers might have identified a new prognostic biomarker for colorectal cancer (CRC).

Primary adenocarcinoma tumor expression levels of messenger RNA for the kallikrein-related peptidase (KLK)-4 gene (KLK4 mRNA) is associated with tumor stage, invasion, size and histological grade, and predicts “poor disease-free survival (DFS), independently of the nodal status and tumor size,” the team reported in the journal Cancer Letters.

KLK4 mRNA expression “constitutes an unfavorable prognostic biomarker in colorectal adenocarcinoma” and “can be regarded as a novel potential tissue biomarker” in CRC, reported lead author Christos K. Kontos of the Department of Biochemistry and Molecular Biology at the University of Athens in Greece, and coauthors.

Circulating carcinoembryonic antigen (CEA) levels are used as a prognostic biomarker for staging and surgical planning, and to monitor treatment response in metastatic CRC, the authors noted. But neither CEA nor other previously proposed prognostic biomarkers in CRC “are sensitive enough,” the authors noted.

New biomarkers “are needed in clinical practice, in order to refine prognostication and predict the benefit derived from systemic treatment of CRC patients,” the authors wrote.

Noting that KLK genes are “aberrantly expressed in cancer, including (CRC),” and that KLK4 activates protease-activated receptor 1 (PAR1) and indirectly activates ERK1/2 in HT-29 CRC cells, the researchers sought to assess KLK4 mRNA expression in CRC as a prognostic biomarker.

Patient follow-up information was available for 62 patients, from whose primary CRC tumors total RNA was collected for KLK4 mRNA PCR expression analysis. The risk of recurrence was a significant correlate of KLK4 mRNA expression level (hazard ratio [HR] 1.37, 95% CI: 1.04-1.81; P=0.024; DFS HR 2.68, 95% CI: 1.06-6.77; P=0.036), the authors found. Overall survival (OS) did not correlate with KLK4 expression, however.

“Furthermore, node-negative patients with colorectal tumors that were positive for KLK4 mRNA tended to relapse earlier than node-negative patients with KLK4 mRNA-negative malignant neoplasms (P<0.001),” they noted.

KLK4 mRNA over-expression is also seen in ovarian cancer and appears to be a biomarker for poor prognosis for patients diagnosed with that malignancy as well, the authors noted. Elevated KLK4 gene transcription has also been reported in prostate and breast cancer, they noted.


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