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The circulating transcriptome (coding and non-coding) plays a critical role in cancer and novel accurate strategies for early
detection of hepatocellular carcinoma (HCC) are strongly needed. We chose a HCC-specific RNA based biomarker panel
based on the integration of differential lysosomal associated membrane protein 2 (LAMP2) gene expressions with its selected
epigenetic regulators using bioinformatic methods. This was followed by RT-qPCR validation in serum of 78 patients with
HCC, 36 patients with chronic hepatitis C (CHC) infection and 44 healthy volunteers. We used risk score analysis to evaluate
the diagnostic efficacy of the serum profiling system. Moreover, in 20 of the 78 HCC cases involved in the study; we examined
the expression of RNA based biomarker panel in both HCC and adjacent non-tumor tissues and assessed their correlation with
the serum level of this panel. The 4 RNA based biomarker panel [long non-coding RNA-C terminal binding protein, androgen
responsive (lncRNA-CTBP), microRNA-16-2 (miR-16-2), microRNA-21-5-P (miR-21-5p) and LAMP2 had high sensitivity
and specificity for discriminating HCC from healthy controls and also from CHC patients. Among these 4 RNAs serum miR-
16-2 and miR-21-5p were independent prognostic factors. The circulatory RNA based biomarker panel can serve as a potential
biomarker for HCC diagnosis and prognosis.