Elevated expression patterns of P-element Induced Wimpy Testis (PIWI) transcripts are potential candidate markers for Hepatocellular Carcinoma

Abstract

BACKGROUND: P-Element-induced wimpy testis (PIWI) proteins, when in combination with PIWI-interacting RNA (piRNA), are engaged in the epigenetic regulation of gene expression in germline cells. Different types of tumour cells have been found to exhibit abnormal expression of piRNA, PIWIL-mRNAs, and proteins. We aimed to determine the mRNA expression profiles of PIWIL1, PIWIL2, PIWIL3, & PIWIL4, in hepatocellular carcinoma patients, and to associate their expression patterns with clinicopathological features. METHODS: The expression patterns of PIWIL1, PIWIL2, PIWIL3, PIWIL4 mRNA, was assessed via real-time quantitative polymerase chain reaction (RT-QPCR), on tissue and serum samples from HCC patients, their impact for diagnosis was evaluated by ROC curves, prognostic utility was determined, and In Silico analysis was conducted for predicted variant detection, association with HCC microRNAs and Network Analysis. RESULTS: Expression levels were significantly higher in both HCC tissue and serum samples than in their respective controls (p< 0.001). Additionally, the diagnostic performance was assessed, Risk determination was found to be statistically significant. CONCLUSION: PIWIL mRNAs are overexpressed in HCC tissue and serum samples, the expression patterns could be valuable molecular markers for HCC, due to their association with age, tumour grade and pattern. To the best of our knowledge, our study is the first to report the expression levels of all PIWIL mRNA and to suggest their remarkable values as diagnostic and prognostic biomarkers, in addition to their correlation to HCC development. Additionally, a therapeutic opportunity might be also suggested through in silico miRNA prediction for HCC and PIWIL genes through DDX4 and miR-124-3p.

New challenges in hepatocellular carcinoma: A role for PIWI-interacting RNAs?

“…These results suggest that Hiwi is a potentially useful HCC biomarker and a valuable new therapeutic target[ 24 ]. Recently, Hammad et al [ 25 ] investigated the mRNA expression levels of PIWI family members [(1) PIWIL1; (2) PIWIL2; (3) PIWIL3; and (4) PIWIL4] in both tissues and serum of HCC patients. Their results showed significant overexpression of these mRNAs in 50 tumour tissues compared to adjacent normal tissues and in 50 HCC sera compared to those of 25 healthy controls.…”

“…Their results showed significant overexpression of these mRNAs in 50 tumour tissues compared to adjacent normal tissues and in 50 HCC sera compared to those of 25 healthy controls. Furthermore, a significant correlation was found between PIWIL1-4 overexpression and advanced tumour stage, at least as far as the tissue samples are concerned[ 25 ]. With high-throughput technologies, it is now possible to extend the investigations to a large number of patients, as well as to deepen the molecular mechanisms in cellular models.…”