Effects of genetic polymorphisms of LINC-PINT gene on liver cancer susceptibility in the Chinese Han population.

Objective: Liver cancer (LC) is the most common cause of cancer mortality. This study aimed to explore the impact of LINC-PINT polymorphisms on LC. Materials & methods: The authors recruited 591 LC patients and 592 healthy controls. The association between LINC-PINT polymorphisms and susceptibility to LC was determined by logistic regression analysis. Results: The authors found that rs157916 and rs16873842 reduced susceptibility to LC. rs157916 decreased LC risk in patients aged <55 years, nondrinkers and those with BMI <24. rs16873842 had a protective role against LC in patients aged ≥55 years, women, nonsmokers and those with BMI ≥24. rs7801029 decreased LC risk in patients with BMI <24. rs28662387 increased LC risk in women. Conclusion: LINC-PINT polymorphisms exert a protective effect against LC.

Contribution of PNPLA3 gene polymorphisms to hepatocellular carcinoma susceptibility in the Chinese Han population.

OBJECTIVES: The purpose of this study was to investigate the association of PNPLA3 single nucleotide polymorphisms (SNPs) (rs738409 C > G, rs3747207 G > A, rs4823173 G > A, and rs2896019 T > G) with hepatocellular carcinoma (HCC) susceptibility. METHODS: This case-control study included 484 HCC patients and 487 controls. Logistic regression analysis was performed to study the associations of PNPLA3 gene polymorphisms with HCC susceptibility, and odds ratios with their corresponding 95% confidence intervals were calculated to evaluate these correlations. RESULTS: In the overall analysis, we found that the G allele (OR = 1.25, 95% CI = 1.04-1.50, p = 0.018, false discovery rate (FDR)-p = 0.035) and GG genotype (OR = 1.59, 95% CI = 1.06-2.39, p = 0.024, FDR-p = 0.048) of rs2896019 were significantly associated with increased HCC susceptibility. In stratified analysis, we found that all four SNPs were related to increased HCC susceptibility in subjects aged > 55 years. In haplotype analysis, the GAAG haplotype was significantly associated with increased HCC susceptibility (OR = 1.25, 95% CI = 1.03-1.53, p = 0.023, FDR-p = 0.046). Besides, we noticed that rs738409 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.007), and HCC patients with the GG genotype had a higher level of AFP. CONCLUSIONS: Our study suggested that PNPLA3-rs2896019 was significantly associated with an increased susceptibility to HCC.

Expression changes of miRNA-203 before and after transcatheter arterial chemoembolization in hepatocellular carcinoma patients and its clinical significance.

PURPOSE: We aimed to detect expression changes of miRNA-203 in the serum of hepatocellular carcinoma (HCC) patients before and after transarterial chemoembolization (TACE), and to explore the clinical significance in influencing the prognosis of HCC. METHODS: Serum levels of miRNA-203 in HCC patients (n=100) and healthy subjects (n=100) were detected by RT-PCR. The relationship between miRNA-203 level and baseline characteristics of HCC was analyzed by Pearson correlation test. The prognostic potentials of miRNA-203 in HCC were evaluated by Kaplan-Meier method. Changes in miRNA-203 level before and after TACE in HCC patients were determined. Cox regression model was applied for analyzing potential factors that may influence the prognosis in HCC. RESULTS: MiRNA-203 was lowly expressed in the serum of HCC patients than in controls. Its level was closely linked to differentiation, metastasis and TNM stage. Serum level of miRNA-203 in HCC patients was upregulated following TACE. Overall survival was better in HCC patients expressing high level of miRNA-203 at post-TACE. Age (over 60 years), large tumor size (≥ 5 cm), metastasis and stage III-IV were risk factors of HCC death, while highly expressed miRNA-203 was a favorable factor. CONCLUSIONS: Serum level of miRNA-203 is downregulated in HCC patients, which is upregulated following TACE. MiRNA-203 can be used to evaluate the prognosis in TACE-treated HCC patients.

Application of the Preoperative Assistant System Based on Machine Learning in Hepatocellular Carcinoma Resection.

To conduct better research in hepatocellular carcinoma resection, this paper used 3D machine learning and logistic regression algorithm to study the preoperative assistance of patients undergoing hepatectomy. In this study, the logistic regression model was analyzed to find the influencing factors for the survival and recurrence of patients. The clinical data of 50 HCC patients who underwent extensive hepatectomy (≥4 segments of the liver) admitted to our hospital from June 2020 to December 2020 were selected to calculate the liver volume, simulated surgical resection volume, residual liver volume, surgical margin, etc. The results showed that the simulated liver volume of 50 patients was 845.2 + 285.5 mL, and the actual liver volume of 50 patients was 826.3 ± 268.1 mL, and there was no significant difference between the two groups (t = 0.425; P > 0.05). Compared with the logistic regression model, the machine learning method has a better prediction effect, but the logistic regression model has better interpretability. The analysis of the relationship between the liver tumour and hepatic vessels in practical problems has specific clinical application value for accurately evaluating the volume of liver resection and surgical margin.

miR-188-5p inhibits proliferation, migration, and invasion in gallbladder carcinoma by targeting Wnt2b and Smad2.

Gallbladder carcinoma (GBC) commonly occurs in gastrointestinal malignancy and has the fifth highest mortality rate among gastrointestinal malignancy. Recently, miR-188-5p, a small noncoding RNA, has been implicated in various types of cancer such as nasopharyngeal carcinoma, oral squamous cell carcinoma, liver cancer, and prostate cancer. However, the effect of miR-188-5p on GBC remains unclear. Here, we demonstrated that miR-188-5p was downregulated in GBC tissues, and downregulation of miR-188-5p correlated with larger tumor size, lymph node metastasis, and extensive metastasis. In addition, the overall survival time of patients with higher miR-188-5p expression was significantly longer than that of patients with low-miR-188-5p expression. Moreover, downregulation of miR-188-5p promoted the proliferation, migration, and invasion of GBC cells, while its overexpression inhibited cell invasion and induced cell apoptosis, and arrested GBC growth in vivo. Importantly, miR-188-5p-dependent tumorigenesis was correlated with Wnt/ß-catenin signaling and p-38/JNK signaling. In conclusion, miR-188-5p plays a direct role in GBC tumorigenesis. Our study suggests that miR-188-5p could serve as a novel diagnosis marker and therapeutic target in GBC.

miR-597-5p inhibits cell growth and promotes cell apoptosis by targeting ELK1 in pancreatic cancer.

Pancreatic cancer is a malignant disease with poor prognosis. Emerging evidences have showed that miR-597-5p is closely related to tumor development. However, the functional roles of miR-597-5p in pancreatic cancer remain unknown. This study aimed to investigate the expression of miR-597-5p in pancreatic cancer tissues and cells, and explored its regulatory mechanism during pancreatic cancer progression. Pancreatic cancer and adjacent tissues were obtained to detect the expression of miR-597-5p by RT-qPCR. Cell growth, apoptosis, and related protein expression were, respectively, tested by CCK-8 assay, cell formation, wound healing, Transwell assay, flow cytometry, and western blotting. Finally, the pancreatic cancer mice model was constructed. In vitro and in vivo results showed that miR-597-5p expression was down-regulated in pancreatic cancer tissues and cell lines, and increased the overall survival of pancreatic cancer patients. Moreover, miR-597-5p decreased pancreatic cancer cell viability, reduced relative wound width, suppressed colony formation and decreased invasive cell number, as well as reduced the expression of proliferating cell nuclear antigen (PCNA), Ki67, Cyclin D1, N-cad, and Bcl-2. Meanwhile, it increased pancreatic cancer cell apoptosis and the expression of E-cad, cleaved caspase 3, and Bax. The dual-luciferase reporter assay confirmed miR-597-5p could directly target e-twenty six like-1 (ELK1) oncogene. The reduction of cell growth and the induction of cell apoptosis induced by miR-597-5p were reversed by ELK1. In addition, miR-597-5p inhibited the growth of pancreatic cancer in vivo. This study demonstrated that miR-597-5p may be a novel suppressor of pancreatic cancer. It inhibits pancreatic cancer cell growth and promotes apoptosis by the down-regulation of ELK1 in vitro and in vivo.

Neuritogenic and survival-promoting effects of the P2 peptide derived from a homophilic binding site in the neural cell adhesion molecule.

The neural cell adhesion molecule (NCAM) plays a pivotal role in neural development, regeneration, and plasticity. NCAM mediates adhesion and subsequent signal transduction through NCAM-NCAM binding. Recently, a peptide ligand termed P2 corresponding to a 12-amino-acid sequence in the FG loop of the second Ig domain of NCAM was shown to mimic NCAM homophilic binding as reflected by induction of neurite outgrowth in hippocampal neurons. We demonstrate here that in concentrations between 0.1 and 10 microM, P2 also induced neuritogenesis in primary dopaminergic and cerebellar neurons. Furthermore, it enhanced the survival rate of cerebellar neurons although not of mesencephalic dopaminergic neurons. Moreover, our data indicate that the protective effect of P2 in cerebellar neurons was due to an inhibition of the apoptotic process, in that caspase-3 activity and the level of DNA fragmentation were lowered by P2. Finally, treatment of neurons with P2 resulted in phosphorylation of the ser/thr kinase Akt. Thus, a small peptide mimicking homophilic NCAM interaction is capable of inducing differentiation as reflected by neurite outgrowth in several neuronal cell types and inhibiting apoptosis in cerebellar granule neurons.