Background: Hepatocellular carcinoma (HCC) is a typical malignancy in a background of chronic inflammation. Th17 cells (a major source of IL-17) constitute crucial components of infiltrating inflammatory/immune cells in HCC and can amplify inflammatory response via binding to interleukin-17 receptor (IL-17R). Thus, we investigated the expression and clinical significance of IL-17 and IL-17 receptor family cytokines in HCC. Methods: The expression and prognostic value of IL-17 and IL-17R (A-E) were examined in 300 HCC patients after resection. Six Th17 associated cytokines in serum (n = 111) were quantified using enzyme-linked immunosorbent assays. Phenotypic features of IL-17⁺ CD4⁺ T cells were determined by flow cytometry analysis. Results: High expression of intratumoral IL-17 and IL1-7RE were significantly associated with poorer survival (p = 0.016 and <0.001, respectively) and increased recurrence (both P < 0.001) of HCC patients. Moreover, intratumoral IL-17, individually or synergistically with IL-17RE, could predict HCC early recurrence and late recurrence. Also, peritumoral IL-17RE showed the prognostic ability in HCC (P < 0.001 for OS/TTR). Furthermore, expression levels of Th17 associated cytokines including IL-6, -22, -17R and TNF-α were increased in serum of HCC patients compared to haemangioma patients. Importantly, activated human hepatic stellate cells induced in vitro expansion of IL-17⁺ CD4⁺ T cells. Conclusions: High expression of IL-17 and IL-17RE were promising predictors for poor outcome of HCC patients. The protumor power of IL-17 producing CD4⁺ T cells was probably involved in the crosstalk with different types of inflammatory/immune cells in HCC.

Purpose: Phosphoglycerate dehydrogenase (PHGDH) acts as a key metabolic enzyme in the rate-limiting step in serine biosynthesis and plays an important role in metastasis of several cancers. The aim of this study was to investigate the prognostic value of PHGDH in gastric cancer (GC). Methods: The messenger RNA expression of PHGDH was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of PHGDH was performed on tissue microarray, composed of 482 GC and 64 matched adjacent nontumor tissues acquired from surgery, 20 chronic gastritis, 18 intestinal metaplasia, and 31 low-grade and 66 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsy. Univariate and multivariate Cox proportional hazard models were used to perform survival analyses. Results: Both PHGDH messenger RNA and protein product exhibited GC tissue-preferred expression, when compared with benign tissues. The high PHGDH expression was significantly correlated with histological type (P=0.011), tumor stage (P=0.014), and preoperative carcinoembryonic antigen (P<0.001). A negative correlation was found between PHGDH expression and the 5-year survival rate of patients with GC. Furthermore, multivariate analysis indicated that PHGDH was an independent prognostic factor for outcome in GC. Conclusion: PHGDH is important in predicting patient outcomes and is a potential target for the development of therapeutic approaches to GC.

Background: Peritumoral activated hepatic stellate cells (HSCs) are versatile myofibroblast-like cells closely related with hepatocellular carcinoma (HCC) progression. So far, comprehensive comparison of gene expression of human HSCs during hepatocarcinogenesis is scanty. Therefore, we identified the phenotypic and genomic characteristics of peritumoral HSCs to explore the valuable information on the prognosis and therapeutic targets of HBV related HCC. Methods: A tissue microarray containing 224 HBV related HCC patients was used to evaluate the expression of phenotype markers of HSCs including α-SMA, glial fibrillary acidic protein (GFAP), desmin, vinculin and vimentin. HSCs and cancer associated myofibroblasts (CAMFs) were isolated from normal, peritumoral human livers and cancer tissues, respectively. Flow cytometry and gene microarray analysis were performed to evaluate the phenotypic changes and gene expression in HCC, respectively. Results: Peritumoral α-SMA positive HSCs showed the prognostic value in time to recurrence (TTR) and overall survival (OS) of HCC patients, especially in early recurrence and AFP-normal HCC patients. Expression of GFAP positive HSCs cell lines LX-2 was significantly decreased after stimulation with tumor conditioned medium. Compared with quiescent HSCs, peritumoral HSCs and intratumoral CAMFs expressed considerable up- and down-regulated genes associated with biological process, cellular component, molecular function and signaling pathways involved in fibrogenesis, inflammation and progress of cancer. Conclusions: Peritumoral activated HSCs displayed prognostic value in HBV related-HCC, and their genomic characteristics could present rational biomarkers for HCC risk and promising therapeutic targets.

Kinesin family protein 2A (KIF2A), an M-type nonmotile microtubule depolymerase, has attracted attention for its role in carcinogenesis and poor prognoses in various human cancers. In this study, we aimed to evaluate the expression of KIF2A and its robustness and potential to predict clinical outcomes in gastric cancer (GC) patients. The messenger RNA (mRNA) expression of KIF2A was determined in 24 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of KIF2A was performed on a tissue microarray composed of 461 GC and 65 matched adjacent nontumor tissues removed during surgeries and 18 chronic gastritis, 15 intestinal metaplasia, and 37 low-grade and 62 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsies. Univariate and multivariate Cox regression models were used to perform survival analyses. The high KIF2A expression was significantly correlated to histological type, TNM stage, and lymph node metastasis. A negative correlation was found between KIF2A expression and the 5-year survival rate of GC patients. In addition, multivariate analysis indicated that KIF2A is an independent prognostic factor in GC. This study demonstrated the high KIF2A expression might serve as an independent marker for poor prognoses in GC patients.

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.

Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in various types of tumors. The presnet study examined the clinical significance of EBI3 expression for predicting tumor recurrence and survival after resection in hepatocellular carcinoma (HCC). EBI3 expression in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples were detected using western blot analysis. Immunohistochemical staining using tissue microarray with 312 samples from randomly selected patients with HCC who underwent surgery. Survival analysis was performed using univariate and multivariate analyses. EBI3 protein level was higher in L‑02 cells and in peri‑tumor tissues compared with tumor tissues. Immunohistochemical staining of EBI3 was reduced in HCC tissues in comparison with adjacent normal tissues and significantly associated with tumor invasive characteristics, including tumor thrombus, poor differentiation and large size. Notably, the results suggested that EBI3 was a predictor for tumor recurrence and patient survival, and multivariate analysis indicated EBI3 to be an independent prognostic factor. Even in early‑stage disease, low EBI3 expression was also independently associated with increased tumor recurrence and shortened survival. Downregulation of EBI3 in HCC indicated aggressive tumor behaviors and predicted a more severe clinical outcome, which suggests that EBI2 may be a useful biomarker to identify patients at high risk of post-operative recurrence.