Prognosis of untreated hepatocellular carcinoma

Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Pecorelli, Anna; Rapaccini, Gian Lodovico; Marco, Mariella Di; Benvegnù, Luisa; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Chiaramonte, M.; Trevisani, Franco

doi:10.1002/hep.27443

Cited by 210 publications

(179 citation statements)

References 33 publications

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“…To date, there is no effective treatment for HCC, and the lack of effective diagnostic techniques available, due to the undefined etiology and pathogenesis and high-grade malignancy, contributes to poor patient prognosis (2). Ascertaining the origin and development of liver cancer and identification of novel targets for therapy have been the focus of recent studies regarding HCC (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Tang

Liang

et al. 2015

Oncology Letters

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Abstract. In order to explore the regulation of the invasive ability of hepatocellular carcinoma cells and the underlying mechanism, mimics sequences of microRNA (miR)-125a (miR-125a-3p/5p) and scramble sequences (miR-125a-3p-s/5p-s) were transfected into human hepatocellular carcinoma cell lines, HCC-LM3 and HepG2, and the non-malignant epithelioid hepatic cell line QZG. To inhibit and upregulate the expression of miR-125a individually. Protein expression was detected by western blotting, and the cell proliferation and migration abilities were evaluated by soft agar colony formation and Transwell assay, respectively. It was revealed that the expression of miR-125a was downregulated in HepG2 and HCC-LM3 cells compared with that of QZG cells, and expression was markedly lower in HCC-LM3 cells than that in HepG2 cells (P<0.01). The colony formation and migration rates of the cells transfected with miR-125a-3p/5p were decreased compared with negative controls, but were increased in cells transfected with miR-125a-3p-3/5p-s (P<0.01). The protein and messenger RNA expression of phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) was decreased following transfection with miR-125a-5p, whereas expression was increased compared with negative controls following transfection with miR-125a-5p-s (P<0.01). Furthermore, the proliferation and migration abilities of cells were attenuated following inhibition of the PI3K/AKT/mTOR pathway by LY294002. The results of the present study indicated that miR-125a inhibits the invasive ability of hepatocellular carcinoma cells via regulation of the PI3K/AKT/mTOR pathway.

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Section: Introductionmentioning

confidence: 99%

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

Tang

Liang

et al. 2015

Oncology Letters

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“…Existing prognostic factors such as serum alpha-fetoprotein (AFP), multinodular tumors, [3] tumor Barcelona-clinic liver cancer (BCLC) stage, [3] and tumor size have been identified in previous studies, their prognostic value warrants more investigation and broader applications. However, they have limitations to some extent in sensitivity and specificity.…”

Section: Introductionmentioning

confidence: 99%

The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection

Liao

et al. 2016

Medicine

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A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients.A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection.

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“…Likewise, a recent study indicated that overall median survival of untreated patients with HCC is about 9 months [6]. The poor prognosis is thought to be a result of several factors.…”

Section: Literature Reviewmentioning

confidence: 99%

Potential Molecular Targets and Drugs for Treatment of Hepatocellular Carcinoma

Mekuria¹,

Abdi²

2017

J Cancer Sci Ther

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Hepatocellular Carcinoma (HCC) is a common type of primary liver cancer. According to the recent world cancer report, the disease ranked as the sixth most common cancer worldwide and the third largest cause of cancer-related death. Deregulation of numerous signaling pathways have been implicate in pathogenesis of HCC, including IGF, EGF/TGF, HGF/cMet, WNT, Hedgehog, notch, hippo, VEGF, PDGF, and FGF. Besides, intracellular mediators such as MAPK and PI3K/AKT/mTOR play a role in HCC development and progression. Currently sorafenib is the only molecularly targeted drug available to treat advanced HCC. It only extends survival by a matter of months. Moreover, there is no alternative agent for patients progressing under treatment with sorafenib. Thus, there remains a critical need for both continued molecular characterization and aggressive drug development. This review provided and updated appraisal of the deregulated signaling and epigenetic pathways, targeted therapeutics that is being investigated and possible challenges in drug development for HCC. Nevertheless, c-Met over-expression was reported to be related to increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition [26]. Pathways related to neo-angiogenesisHigh vascularization is a hallmark of human HCC [8]. This angiogenesis process relies on autocrine and paracrine interactions between tumor cells, vascular endothelial cells, and pericytes. Tumor cells release pro-angiogenic factors in response to hypoxic conditions and nutrient deprivation and thus activate endothelial cells [27]. Activated endothelial cells break down extracellular matrix and basement membrane which result in a release of angiogenic factors which includes VEGF, FGF, PDGF, and TGF β [16]. These angiogenic factors in turn activate endothelial cells through TKR and their intracellular mediator's MAPK and PI3K/Akt/mTOR pathways, which lead to proliferation and migration of endothelial cells to form a new tubular structure and lumen for new vessels and finally, pericytes are activated and recruited to stabilize the new blood vessels [27,28]. has become a potential investigating area of research to identify target(s) to inhibit proliferation of HCC and metastasis. IGF pathwayThe pathway consists of circulating ligands IGF-I, IGF-II, and the receptor IGF-IR. It has been known for its involvement in the regulation of cell growth and energy metabolism [17]. According to studies, overexpression of IGF-II and IGF-IR has been implicated in cell proliferation and inhibition of apoptosis [18]. In support of this, low expression of IGF I and progressive increase in the level of expression of IGF-IR, IGF-II, and IGF substrates during the hepatocarcinogenesis process was detected at mRNA and protein level, which was associated with cell increased proliferation and reduced apoptosis has been observed in HCC cell lines and rat models as well as in human HCC samples [18]. Other studies also indicated that the major tumorpromoting e...

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Prognosis of untreated hepatocellular carcinoma

Cited by 210 publications

References 33 publications

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection

Potential Molecular Targets and Drugs for Treatment of Hepatocellular Carcinoma

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