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Review
. 2018 Jul 26;399(8):821-836.
doi: 10.1515/hsz-2017-0342.

Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies

Panagiotis G Adamopoulos  1 , Panagiotis Tsiakanikas  1 , Andreas Scorilas  1
Affiliations
Review

Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies

Panagiotis G Adamopoulos et al. Biol Chem. .

Abstract

Gastrointestinal (GI) malignancies represent a wide spectrum of diseases of the GI tract and its accessory digestive organs, including esophageal (EC), gastric (GC), hepatocellular, pancreatic (PC) and colorectal cancers (CRC). Malignancies of the GI system are responsible for nearly 30% of cancer-related morbidity and approximately 40% of cancer-related mortality, worldwide. For this reason, the discovery of novel prognostic biomarkers that can efficiently provide a better prognosis, risk assessment and prediction of treatment response is an imperative need. Human kallikrein-related peptidases (KLKs) are a subgroup of trypsin and chymotrypsin-like serine peptidases that have emerged as promising prognosticators for many human types of cancer, being aberrantly expressed in cancerous tissues. The aberrant expression of KLKs in human malignancies is often regulated by KLK/microRNAs (miRNAs) interactions, as many miRNAs have been found to target KLKs and therefore alter their expression levels. The biomarker utility of KLKs has been elucidated not only in endocrine-related human malignancies, including those of the prostate and breast, but also in GI malignancies. The main purpose of this review is to summarize the existing information regarding the prognostic significance of KLKs in major types of GI malignancies and highlight the regulatory role of miRNAs on the expression levels of KLKs in these types of cancer.

Keywords: colorectal cancer; esophageal cancer; gastric cancer; hepatocellular carcinoma; ncRNAs; pancreatic carcinoma.

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References

    1. Adamopoulos, P.G., Kontos, C.K., Papageorgiou, S.G., Pappa, V., and Scorilas, A. (2015a). KLKB1 mRNA overexpression: a novel molecular biomarker for the diagnosis of chronic lymphocytic leukemia. Clin. Biochem. 48, 849–854.
    1. Adamopoulos, P.G., Kontos, C.K., Rapti, S.M., Papadopoulos, I.N., and Scorilas, A. (2015b). miR-224 overexpression is a strong and independent prognosticator of short-term relapse and poor overall survival in colorectal adenocarcinoma. Int. J. Oncol. 46, 849–859.
    1. Adamopoulos, P.G., Kontos, C.K., Tsiakanikas, P., and Scorilas, A. (2016). Identification of novel alternative splice variants of the BCL2L12 gene in human cancer cells using next-generation sequencing methodology. Cancer Lett. 373, 119–129.
    1. Adamopoulos, P.G., Kontos, C.K., and Scorilas, A. (2017a). Identification and molecular cloning of novel transcripts of the human kallikrein-related peptidase 10 (KLK10) gene using next-generation sequencing. Biochem. Biophys. Res. Commun. 487, 776–781.
    1. Adamopoulos, P.G., Kontos, C.K., and Scorilas, A. (2017b). Molecular cloning of novel transcripts of human kallikrein-related peptidases 5, 6, 7, 8 and 9 (KLK5–KLK9), using next-generation sequencing. Sci. Rep. 7, 17299.

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