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CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported.

The permeability tensor is a critical parameter for analyzing the hydraulic behavior of anisotropic permeability in fractured rock masses. However, determining this tensor for three-dimensional (3D) fractured rock masses has proven to be challenging and resource-intensive. Both field tests, requiring numerous costly in situ tests, and numerical experiments, hindered by complex discrete fracture networks with a high fracture density, present difficulties in obtaining accurate results. In response, this study proposes a semi-theoretical method for determining the permeability tensor of 3D fractured rock masses, significantly reducing labor and economic costs. The proposed method focuses on establishing the theoretical relationship of directional permeabilities in a 3D space, with emphasis on the properties of the permeability tensor and the influence of fractures' geometry on the flow rate. To facilitate the construction of the method, anisotropic ellipse and ellipsoid are introduced, providing a description of permeability anisotropy. With this innovative approach, engineers can calculate the permeability tensor even when only one value of permeability is available along any flow direction. The utilization of the anisotropic ellipse and ellipsoid concepts helps simplify the determination process. Through numerical experiments, the method is validated and its accuracy demonstrated, making it a valuable tool for analyzing the hydraulic behavior of 3D fractured rock masses. [ABSTRACT FROM AUTHOR]

We aim to investigate the expression and clinical significance of the tubulin gamma complex-associated protein 4 (TUBGCP4) in hepatocellular carcinoma (HCC). The mRNA expression of TUBGCP4 in HCC tissues was analyzed using The Cancer Genome Atlas (TCGA) database. Paired HCC and adjacent nontumor tissues were obtained from HCC patients to measure the protein expression of TUBGCP4 by immunohistochemistry (IHC) and to analyze the relationship between TUBGCP4 protein expression and the clinicopathological characteristics and the prognosis of HCC patients. We found that TUBGCP4 mRNA expression was upregulated in HCC tissues from TCGA database. IHC analysis showed that TUBGCP4 was positively expressed in 61.25% (49/80) of HCC tissues and 77.5% (62/80) of adjacent nontumor tissues. The Chi-square analysis indicated that the positive rate of TUBGCP4 expression between HCC tissues and the adjacent nontumor tissues was statistically different (P < 0.05). Furthermore, we found that TUBGCP4 protein expression was correlated with carbohydrate antigen (CA-199) levels of HCC patients (P < 0.05). Further, survival analysis showed that the overall survival time and tumor-free survival time in the TUBGCP4 positive group were significantly higher than those of the negative group (P < 0.05), indicating that the positive expression of TUBGCP4 was related to a better prognosis of HCC patients. COX model showed that TUBGCP4 was an independent prognostic factor for HCC patients. Our study indicates that TUBGCP4 protein expression is downregulated in HCC tissues and has a relationship with the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

As an important transcription factor that is widely expressed in most tissues of the human body, Myc‐associated zinc finger protein (MAZ) has been reported highly expressed in many malignant tumors and thought to be a promising therapeutic target for cancer treatment. In this review, we aim to offer a comprehensive understanding of MAZ regulation in malignant tumors. The carboxy terminal of MAZ protein contains six C2H2 zinc fingers, and its regulation of transcription is based on the interaction between the GC‐rich DNA binding sites of target genes and its carboxy‐terminal zinc finger motifs. MAZ protein has been found to activate or inhibit the transcriptional initiation process of many target genes, as well as play an important role in the transcriptional termination process of some target genes, so MAZ poses dual regulatory functions in the initiation and termination process of gene transcription. Through the transcriptional regulation of c‐myc and Ras gene family, MAZ poses an important role in the occurrence and development of breast cancer, pancreatic cancer, prostate cancer, glioblastoma, neuroblastoma, and other malignant tumors. Our review shows a vital role of MAZ in many malignant tumors and provides novel insight for cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Tetraspanins (TSPANs) play crucial roles in cell adhesion, migration, and metastasis of human cancer. However, there is no study in revealing the aspects of TSPAN9 traits and its functions in hepatocellular carcinoma (HCC) prognosis. Our study is the first to portray the TSPAN9 expression in HCC tissues with immunohistochemistry (IHC) analysis. Subsequently, a series of bioinformatics analyses such as expression estimation, survival assessment, and correlation analysis were implemented to dig out the possible upstream noncoding RNAs (ncRNAs) for TSPAN9 in HCC. In this way, the relevance within TSPAN9 and tumor immunity was then explored. We found that the TSPAN9 was downregulated in HCC tissues and had a correlation with HCC prognosis. Furthermore, we identified that the AL139383.1-hsa-miR-9-5p axis was the upstream ncRNA-related pathway most associated with TSPAN9 in HCC. Besides that, expression of TSPAN9 held a significantly negative correlation with tumor immunocyte infiltration as well as immune checkpoint CTLA4. TSPAN9-related immunomodulators were mainly enriched in T cell activation, leukocyte cell-cell adhesion, regulation of T cell activation, and regulation of leukocyte cell-cell adhesion signaling pathway. In conclusion, our results indicated that hsa-miR-9-5p-mediated downregulation of TSPAN9 was associated with poor HCC prognosis, immune-related signaling pathway, and tumor immune infiltration. [ABSTRACT FROM AUTHOR]

Background HIV prevalence has been rapidly increasing among men who have sex with men (MSM) attending university in China, but HIV testing rates remain suboptimal. The factors associated with past HIV testing in this population in Beijing, China, were investigated.Methods: This study used data from the baseline survey of an HIV intervention clinical trial among MSM who did not have a history of a positive HIV diagnosis. This analysis focused on the HIV testing experience in a subgroup of university student MSM participants. Log-binomial models were used to evaluate factors associated with past HIV testing.Results: Of 375 university student MSM, the median age was 22 years; 89.3% were Han ethnic. Approximately half (50.4%, n = 189) had ever taken an HIV test before the survey. In a multivariable log-binomial model, older age (adjusted prevalence ratio (APR), 1.04; 95% confidence interval (CI), 1.02-1.06), had first sexual intercourse at age <18 years (APR, 1.35; 95% CI, 1.08-1.45) and knew someone living with HIV (APR, 1.33; 95% CI, 1.07-1.61) were associated with a higher likelihood of past testing. Self-reported barriers to taking a test included perceived low HIV risk, fear of a positive diagnosis, did not know where to get tested and fear of discrimination. Facilitators included anonymity in taking a test, confidentiality of testing results and availability of home-based and rapid testing.Conclusions: The HIV testing rate among university student MSM was low. Interventions should be implemented to address structural, institutional and individual barriers to HIV testing in this vulnerable population. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the expression and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 2 (CMTM2) in hepatocellular carcinoma (HCC) tissues. Bioinformatics analysis showed that CMTM2 was downregulated in HCC tissues and correlated with vascular invasion of HCC patients. The immunohistochemistry (IHC) method found that CMTM2 expression was negative in 29/75 (38.67%) cases of HCC tissues and 13/75 (17.33%) cases of paracancerous tissues, also showed a significantly lower expression of CMTM2 in HCC tissues than the paired paracancerous tissues (p < 0.05). Moreover, CMTM2 expression was significantly correlated with tumor grade of HCC patients (p < 0.05), but had no relationship with other clinicopathological features. In addition, multivariate logistic regression analysis indicated that tumor grade was an independent risk factor for CMTM2 expression. The survival time of HCC patients between high and low expression of CMTM2 had no difference by bioinformatics analysis, but the IHC result showed that the negative expression of CMTM2 was related to a poor prognosis of HCC patients. Further COX regression analysis showed that CMTM2 expression was an independent protective factor for the prognosis of HCC patients. We identify that CMTM2 is downregulated in HCC tissues and correlated with the prognosis of HCC patients, suggesting a potential tumor suppressor role of CMTM2 in HCC progression. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in China, with high metastasis and poor prognosis. Recently, as the core component of the polycomb repressive complexes 1 (PRC1), chromobox protein homolog 8 (CBX8) is considered as an oncogene and prognostic marker in HCC. Methods: A tissue microarray of 166 paired HCC and adjacent non-tumor samples were collected to identify the relationship between CBX8 and epithelial mesenchymal transition (EMT) associated proteins by Spearman correlation analysis. Knock-down of CBX8 in HCC cells was conducted to detect the biologic functions of CBX8 in HCC metastasis. Results: We found out that CBX8 was over-expressed in HCC and its expression was closely related to the metastasis of HCC patients. In addition, knock-down of CBX8 was found to inhibit the invasion and migration ability of HCC cells. Moreover, there was a significant relationship between expression of CBX8 and EMT associated proteins both in HCC cells and tumor tissues. Conclusions: Our results indicate that CBX8 promotes metastasis of HCC by inducing EMT process. [ABSTRACT FROM AUTHOR]

Background. The chromobox (CBX) proteins CBX2, CBX4, CBX6, CBX7, and CBX8, also known as Polycomb (Pc) proteins, are canonical components of the Polycomb repressive complex 1 (PRC1). Abundant evidence indicates that abnormal expression of Pc proteins is associated with a variety of tumors, but their role in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. In the present study, we performed a case-control study to investigate the relationship between single nucleotide polymorphisms (SNPs) of CBX genes and HCC. Methods. Nine SNPs on CBX genes (rs7217395, rs2036316 of CBX2; rs3764374, rs1285251, rs2289728 of CBX4; rs7292074 of CBX6; and rs710190, rs139394, rs5750753 of CBX7) were screened and genotyped using MassARRAY technology in 334 HCC cases and 321 controls. The association between SNPs and their corresponding gene expressions was analyzed through bioinformatics methods using the Ensembl database and Blood eQTL browser online tools. Results. The results indicated that rs2289728 (G>A) of CBX4 (P = 0.03, OR = 0.56, 95% CI: 0.33-0.94) and rs139394 (C>A) of CBX7 (P = 0.02, OR = 0.55, 95% CI: 0.33-0.90) decreased the risk of HCC. Interaction between rs2036316 and HBsAg increased the risk of HCC (P = 0.02, OR = 6.88, 95% CI: 5.20-9.11), whereas SNP-SNP interaction between rs710190 and rs139394 reduced the risk of HCC (P = 0.03, OR = 0.33, 95% CI: 0.12-0.91). Gene expression analyses showed that the rs2289728 A allele and the rs139394 A allele significantly reduced CBX4 and CBX7 expression, respectively. Conclusion. Our findings suggest that CBX4 rs2289728 and CBX7 rs139394 are protective SNPs against HCC. The two SNPs may reduce the risk of HCC while suppressing the expression of CBX4 and CBX7. [ABSTRACT FROM AUTHOR]

This study aimed to examine the expression level and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) in paired hepatocellular carcinoma (HCC) and adjacent nontumor tissues. The expression of CMTM6 was detected in 75 paired HCC and adjacent nontumor tissues by immunohistochemistry. Chi-square test was used to compare the difference of CMTM6 expression between HCC tissues and adjacent nontumor tissues. The clinic-pathological features and prognosis of HCC patients were collected to analyze the relationship with CMTM6 expression. The positive expression of CMTM6 in HCC tissues was significantly lower than that of adjacent nontumor tissues. The difference of CMTM6 expression between HCC tissues and paired adjacent nontumor tissues was statistically significant (p < 0.05). Furthermore, CMTM6 expression was correlated with HCC metastasis and alpha-fetoprotein (AFP) (p < 0.05). Multivariate logistic regression analysis showed tumor staging, metastasis, and AFP had a significant relationship with CMTM6 expression. In addition, the survival time of HCC patients was different between CMTM6 positive group and CMTM6 negative group by Kaplan–Meier survival analysis (p < 0.05). Downregulation of CMTM6 is related to HCC metastasis and the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Polymorphisms in genes may affect its expression and alter individual susceptibility to cancer. In this study, we investigate associations between CMTM family gene polymorphisms and hepatocellular carcinoma (HCC) in a southern Chinese population. Ten selected single-nucleotide polymorphisms (SNPs) in CMTM family genes were genotyped in 315 HCC patients and 315 cancer-free controls using Sequenom MassARRAY platform and the associations of the selected SNPs with HCC risk were evaluated. We found individuals with the rs164207 AA genotypes had a significantly increased risk of HCC than those with CC genotypes (adjusted OR = 2.794, 95% CI = 1.143–6.828). Also, individuals with the rs3811178 GG genotypes showed a significant association with increased risk of HCC when compared with the AA genotypes (adjusted OR = 2.578, 95% CI = 1.114–5.969). Furthermore, there was also a significantly increased risk of HCC when combined risk genotypes of these loci, i.e., rs164207 AA, CA and rs3811178 GG, GA. Compared with the low-risk group (0 risk genotypes), the high-risk group (2 risk genotypes) was at significantly increased risk of HCC (adjusted OR = 3.339, 95% CI = 1.119–9.964, p = 0.031). Our results suggest that polymorphisms of rs3811178 in CMTM5 and rs164207 in CMTM6 might contribute to the genetic susceptibility of HCC in the southern Chinese population. Further well-designed studies with larger sample sizes are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

The defects of DNA repair genes may lead to genomic instability and cancer. As an important DNA mismatch repair gene that maintains genomic stability from DNA replication errors, genetic variants of mutS homolog 2 (MSH2) are associated with some cancers. In this study, 1021 hepatocellular carcinoma (HCC) cases and 1021 non-HCC controls from Guangxi were included to explore the association between MSH2 single-nucleotide polymorphisms (SNPs) and HCC. Among the eight MSH2 SNPs, only genotype distribution of rs2303428 was significantly different from HCC and non-HCC patients ( p < 0.05). Moreover, CT, TT, and CT/TT genotype of rs2303428 could increase HCC risk [OR (95% CI) = 1.758 (1.195-2.657), 1.846 (1.213-2.896), and 1.823 (1.219-2.763), respectively] and decrease the survival time of HCC patients [codominant, HR (95% CI) = 1.267 (1.046-1.535); dominant, HR (95% CI) = 1.675 (1.162-2.414)]. In addition, rs2303428 was found to interact with HBV infection and family history to increase HCC risk by gene-environment analysis ( p < 0.05). Finally, multivariate COX regression analysis showed that rs2303428, tumor number, tumor staging, and metastasis had a significant influence on HCC prognosis. Our results provide MSH2 SNP, rs2303428, as a new prognostic biomarker for HCC patients. [ABSTRACT FROM AUTHOR]

The forkhead box O (FOXO) transcription factors play important roles in various cancer development including Hepatocellular Carcinoma (HCC). In this study we conducted a hospital-based case control study including 1049 cases (HCC patients) and 1052 controls (non-tumor patients) to examine whether single nucleotide polymorphisms (SNPs) within microRNA (miRNA) target sites of FOXO genes confer HCC susceptibility. A total of three miRNA target site SNPs in the 3’ untranslated regions (UTR) of FOXO1 (rs17592236), FOXO3 (rs4946936) and FOXO4 (rs4503258) were analyzed. No statistically significant differences were found in genotype distribution for rs17592236, rs4946936, and rs4503258 between the HCC patient group and the tumor-free control group using single factor chi-square analysis (P>0.05). However, multivariate logistic regression analysis showed that the CT/TT genotype in rs17592236 was significantly associated with decreased risk of HCC development (P = 0.010, OR = 0.699, 95% CI: 0.526–0.927) as compared to the CC genotype in rs17592236. Additionally, a genetic interaction was found between rs17592236 and rs4503258 (P = 0.003, OR = 0.755, 95% CI: 0.628–0.908). Functional dual luciferase reporter assays verified that the rs17592236 SNP was a target site of human miRNA miR-137. Together, these results indicate that the rs17592236 polymorphism is associated with decreasing of HCC hereditary susceptibility likely through modulating the binding affinity of miR-137 to the 3’UTR in FOXO1 messenger RNA (mRNA). Further knowledge obtained from this study may provide important evidence for the prevention and targeted therapy of HCC. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]