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Background: The liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions. Methods: From January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods. Results: Median follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS. Conclusions: Simultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.

Background: Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported. Thus, we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC. Methods: A thorough literature search using PubMed (Medline), Embase, Cochrane Library, Web of Science databases, and Chinese Science Citation Database was conducted to obtain the relevant studies. Pooled hazard ratios (HR s) or odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the results. Results: A total of 11 studies were finally enrolled in this meta-analysis. Compared with patients with lower ERCC1 expression, patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR = 2.325, 95% CI: 1.720–3.143, P < 0.001), progression-free survival (PFS) (HR = 1.917, 95% CI: 1.366–2.691, P < 0.001) and poor response to chemotherapy (OR = 0.491, 95% CI: 0.243–0.990, P = 0.047). Subgroup analyses by treatment setting, ethnicity, HR extraction, detection methods, survival analysis, and study design demonstrated that our results were robust. Conclusions: ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy, OS, and PFS. Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC1's prognostic value.

Background: Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients. Methods: This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic. Results: The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389). Conclusions: BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers.We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) of overall survival (OS) and disease-free survival (DFS) were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated.A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001) and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035) in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR) = 1.895, 95% CI: 1.364-2.632, P < 0.001) and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis.Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.

Abstract Background MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated. Methods We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip. Results Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/β-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3miR-612-OE and HCCLM3 hadha-KD cells were decreased nearly by 40% and 60% of their counterparts (p 0.05) or 1/2 (p

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Accumulation of evidence indicates that miRNAs have crucial roles in the regulation of EMT-associated properties, such as proliferation, migration and invasion. However, the underlying molecular mechanisms are not entirely illustrated. Here, we investigated the role of miR-296-5p in hepatocellular carcinoma (HCC) progression. Methods In vitro cell morphology, proliferation, migration and invasion were compared between HCC cell lines with up- or down-regulation of miR-296-5p. Immunofluorescence and Western blot immunofluorescence assays were used to detect the expression of EMT markers. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-296-5p. Xenograft nude mouse models were established to observe tumor growth and metastasis. Immunohistochemical assays were conducted to study the relationships between miR-296-5p expression and Neuregulin-1 (NRG1)/EMT markers in human HCC samples and mice. Results miR-296-5p was prominently downregulated in HCC tissues relative to adjacent normal liver tissues and associated with favorable prognosis. Overexpression of miR-296-5p inhibited EMT along with migration and invasion of HCC cells via suppressing NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling in vitro. More importantly, miR-296-5p disrupted intrahepatic and pulmonary metastasis in vivo. NRG1, as a direct target of miR-296-5p, mediates downstream biological responses. In HCC tissues from patients and mice, the levels of miR-296-5p and NRG1 also showed an inverse relationship. Conclusions miR-296-5p inhibited EMT-related metastasis of HCC through NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling.

Objective To establish a sandwich ELISA method for detecting vascular endothelial growth factor (VEGF) in sera of population and the patients with hepatocellular carcinoma (HCC). Methods Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coil in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein 0, a sandwich ELISA technique was established. Serum VEOF levels were evaluated in 229 adults and 291 HCC patients. Results SDS-PAGE displayed that the molecular weights of the expressed full length (His-Trx-VEGF1-165), N-terminal (His-Trx-VEGF1-100) and C-terminal (GST-VEGF100-165) human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R²=0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference. Conclusion The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index. [ABSTRACT FROM AUTHOR]