Hepatocellular carcinoma (HCC) is one of the most common malignancies globally and the second leading cause of cancer-related death. Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is one of the commonly mutated genes in HCC, but its role in HCC remains unclear. In this study, we analyzed the role of LRP1B mutation in HCC. The bioinformatics results show that LRP1B had a frequency of mutation in HCC patients, and LRP1B mutation was associated with a higher tumor mutation burden (TMB), and survival analysis proved that the prognosis of HCC patients with LRP1B mutation was poor. Univariate and multivariate COX regression analysis indicated that LRP1B mutation was an independent risk factor in evaluating HCC patients' prognosis. Correlation analysis showed that LRP1B mutation status was associated with the infiltration of 2 types of immune cells and higher expression of immune checkpoint gene human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) in HCC patients. In summary, the results show that LRP1B mutation is associated with the higher TMB and poor prognosis of patients with HCC, and it was an independent risk factor for clinical outcomes of HCC patients. LRP1B gene mutations can serve as predictors in HCC patients with higher TMB and higher expression of HHLA2. The results of this study will be beneficial to future studies on targeted therapy and immunotherapy for HCC.

ABSTRACT. Human cytochrome P450 4A11 (CYP4A11) plays a role in the regulation of blood pressure through the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE). We therefore investigated the association between a CYP4A11 polymorphism (rs9333025) with hypertension in the Mongolian and Han ethnic groups. We studied 514 Mongolians in a pastoral area, including 201 hypertension patients and 313 normotensive controls, and 524 Han individuals in an urban area, including 215 hypertension patients and 309 normotensive controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Genotype, allele, and dominant inheritance differed significantly between the Mongolian and Han populations (P = 0.006, P = 0.002, and P = 0.003, respectively). Significant differences were also observed in these factors when considering only males (P = 0.001, P = 0.003, and P = 0.001, respectively). For the Han population, recessive inheritance differed significantly between hypertension patients and controls and between male patients and controls (P = 0.005 and P = 0.049, respectively). The genotypic, allelic, and dominant frequencies differed significantly between hypertension patients in both populations (P = 0.019, P = 0.035, and P = 0.024, respectively). The genotypic frequency in Mongolian male patients was significantly different from that in Han male patients (P = 0.009). Higher body mass index, triglycerides, and lower high-density lipoprotein were associated with increased risk of developing hypertension in the Han population. The GG genotype was in higher frequency in the Mongolian population, indicating that it is a high risk factor for hypertension. Mongolian men were at higher risk of developing hypertension.

Background: LINC02560 is a new 477 bp long non-coding RNA located in 19q13.43. However, the expression of LINC02560 in colorectal cancer (CRC) has not been reported, and its correlation with tumor development and function is still unclear. Methods: The expression of LINC02560 in CRC was first analyzed in the cancer genome atlas (TCGA) combined with The Genotype-Tissue Expression(GTEx) databases and then validated by clinical CRC samples and cell lines. The association between LINC02560 expression and clinicopathologic variables was analyzed by the Wilcoxon Rank SUM test. Cox regression analysis and Kaplan-Meier plots were used to assess the prognostic value of LINC02560 in CRC. The correlation between the expression level of LINC02560 and the 24 immune cells in tumor microenvironment (TME) was analyzed by single sample gene set enrichment analysis (ssGSEA). Gene set enrichment analysis (GSEA) was conducted to detect potential biological processes associated with LINC02560 in CRC. Results: LINC02560 was significantly up-regulated in CRC in comparison to normal samples. There are significant differences in the expression of LINC02560 in different subgroups of N stage, M stage, carcinoembryonic antigen (CEA) level, residual tumor, TP53 status and pathological stage. The high LINC02560 expression indicated poor overall survival (OS) and progress free interval (PFI) in patients with CRC. Moreover, the multivariate Cox analysis demonstrated that the expression of LINC02560 was an independent prognosis-predicting factor for OS in CRC patients. GSEA indicated that high expression of LINC02560 was involved in MAPK, Wnt, and PPAR signaling pathways and participated in humoral immune processes. We also identified that LINC02560 expression had a negative correlation with 4 kinds of immune cells. Conclusions: In summary, our research results indicate that LINC02560 may be a potential prognostic biomarker. It is involved in the occurrence and development of CRC and may affect the prognosis of CRC patients by regulating immune cells in the TME.

Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC.

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-AT haplotype (OR = 0.69, 95% CI = 0.52-0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.