Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma.

PURPOSE: Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit. METHODS: Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC-) was evaluated. RESULTS: The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC- patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC- , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC- ones, may be not due to the activation of HIF-1α pathway. CONCLUSION: The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients' outcomes and responses to adjuvant TACE therapy.

Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND/AIMS: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. METHODS: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial-mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. RESULTS: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. CONCLUSION: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.

XRCC1 Arg194Trp and Arg399Gln polymorphisms and risk of extrahepatic cholangiocarcinoma: a hospital-based case-control study in China.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECCA) is a rare but devastating malignancy. Up to 90% of patients presenting with ECCA have no identifiable risk factors. The base excision repair (BER) pathway has a principal role in the repair of mutations caused by oxidized or reduced bases. The XRCC1 is one of the key proteins in the BER pathway. In this study, we investigated the influence of XRCC1 Arg194Trp and Arg399Gln polymorphisms on ECCA incidence. METHODS: The study included 189 ECCA patients and 216 controls. Genotypes were detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: For codon 194, the genotype frequencies of C/C, T/C and T/T were 51.3, 43.4 and 5.3%, respectively, in the ECCA cases compared with 54.2, 38.9 and 6.9%, respectively, in the controls. No statistically significant differences were observed in the genotype frequencies of codon 194 between the two groups compared to the control (TC, OR: 0.85, 95% CI: 0.57-1.28, TT, OR: 1.24, 95% CI: 0.54-2.89, TC+TT, OR: 0.89, 95% CI: 0.60-1.32). For codon 399, the genotype frequencies of G/G, G/A and A/A were 54.0, 37.0 and 9.0%, respectively, in the ECCA cases compared with 56.1, 39.8 and 4.1%, respectively, in the controls. No statistically significant differences were observed in the genotype frequencies codon 399 between the two groups compared to the control (GA, OR: 1.04, 95% CI: 0.69-1.56, AA, OR: 0.45, 95% CI: 0.19-1.04, GA+AA, OR: 0.92, 95% CI: 0.62-1.36). Meanwhile, no statistically significant differences were found in the haplotype and risk of developing ECCA compared to the control (CA, OR: 0.83, 95% CI: 0.49-1.39, TG, OR: 0.96, 95% CI: 0.58-1.60, TA, OR: 0.83, 95% CI: 0.38-1.82). CONCLUSION: The present study suggested that Arg194Trp and Arg399Gln polymorphism in the DNA repair gene XRCC1 was not statistically associated with risk of ECCA. It would be necessary to confirm these findings in a large sample size and multiethnic population study in future.