LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma

Abstract

BackgroundThe La-related protein 1 (LARP1) has been found to be a RNA binding protein and was related to spermatogenesis, embryogenesis and cell-cycle progression. The aim of this study was to investigate the prognostic value of LARP1 in hepatocellular carcinoma (HCC).MethodsLARP1 expression was examined in 15 HCC cell lines and 272 clinical specimens using real-time PCR, immunohistochemistry (IHC) and western blot analysis (WB). LARP1 expression was also studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Statistical analyses were applied to derive association between LARP1 expression scores and clinical characters as well as patient survival.ResultsmRNA and protein levels of LARP1 were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. LARP1 expression was correlated to survival time, vital status, tumor size and Child-Pugh score. Overall survival analysis showed HCC patients with high LARP1 expression level had lower survival rate (P < 0.01). Importantly, this correlation remained significant in patients with early-stage HCC or with normal serum AFP level.ConclusionsLARP1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.

A liaison between mTOR signaling, ribosome biogenesis and cancer

“…Among other ribosomal-biogenesis regulating molecules, the RNA binding protein LARP1 was recently shown to promote the stability of mTOR mRNA and sustain downstream mTOR signaling, a mechanism that appears to correlate with cancer progression as shown in human specimens from cervical and non-small cell lung cancers [97]. Similar evidence has been also observed in hepatocellular carcinoma [98]. The anabolic and catabolic processes regulated by mTORC1 span from protein, ribosome, lipid and nucleotide biosynthesis to autophagy and cell survival, respectively.…”

Proteomic analysis of cap-dependent translation identifies LARP1 as a key regulator of 5′TOP mRNA translation

“…As such, LARP1 mRNA was shown to be particularly up-regulated in liver cancer (Chen et al 2002;Wurmbach et al 2007;Roessler et al 2010). In addition, a recent study showed that LARP1 mRNA and protein levels were up-regulated in several hepatocellular carcinoma (HCC) cell lines as well as in HCC patients who concomitantly had a lower survival rate (Xie et al 2013), raising the possibility that LARP1 may serve as a biomarker for predicting the prognosis of HCC. Despite promising preclinical and early clinical results obtained with mTOR inhibitors, resistance of cancer cells to these treatments has been reported.…”

Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target

“…It plays a key role in embryogenesis, oogenesis, spermatogenesis, mitotic spindle formation, mitochondrial segregation, and cell cycle progression [24–26]. Although LARP1 plays an important role in tumorigenesis and progression of cervical cancer, non-small cell lung cancer, HCC, and prostate cancer [10, 18, 27, 28], the biological function and prognostic value of LARP1 expression in human colon cancer are still unknown.…”

“…Recently, LARP1 was shown to be overexpressed in cervical and non-small cell lung cancers, with increased expression correlated with cancer progression and poor prognosis [14]. As a promising biomarker, the expression of LARP1 is closely related to poor prognosis of early-stage and alpha-fetoprotein-normal hepatocellular carcinoma (HCC) patients [18]. Recently, it has been found that downregulation of LARP1 expression in endometrial cancer and lung cancer cell lines was associated with decreased cell proliferation [19].…”