Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV-related hepatocellular carcinoma risk: A system review and meta-analysis.

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.

Biomass-based adsorbents for post-combustion CO2 capture: Preparation, performances, modeling, and assessment.

The adsorbents are critical carriers in the process of adsorption-based post-combustion CO2 capture. Biomass-based adsorbents (BAs) are considered to have great potential because of their high efficiency, low cost, and good sustainability. To understand the methods, theories, and technologies of BAs-based CO2 capture, this work analyzes their preparation and activation/modification, influencing factors, mechanisms, thermodynamics/kinetics, regeneration and cycle performances, and the pathway to application. It is found that BAs prepared by pyrolysis, chemical activation, and modification with dual heteroatoms are more conducive to improving adsorption sites. CO2 adsorption capacity positively correlates with elemental C and fixed carbon of feedstocks, but negatively with moisture. The BAs prepared at 550-600 °C have high performance. The specific surface area (SSA) increases as the preparation time increases by 9.4%-93.4%. The adsorption capacity is positively correlated to the SSA (R = 0.880) and microporous volume (R = 0.773). Moreover, it decreases linearly with increasing operating temperature with the slope of -0.6 mmol/(g·°C) but increases exponentially with increasing operating pressure and CO2 concentration with the power of 0.824. The adsorption process includes physical and/or physicochemical adsorption. Freundlich isotherm equation and pseudo-second-order model characterize the adsorption thermodynamics and kinetics more effectively with R2 = 0.985-1.000 and R2 = 0.894-1.000. The quantum chemistry indicates that most BAs modified with non-metallic belong to physisorption. The regeneration of BAs has low energy consumption (<3.44 MJ/kg CO2) and loss rate (<8%). Furthermore, the technical pathway is proposed for application. Finally, the challenges are also presented to facilitate the development of BAs-CO2 capture.

Influence of clear cell carcinoma on the post-hepatectomy prognosis of patients with hepatocellular carcinoma.

Aim: The authors aimed to identify factors that independently influence the survival of patients with primary clear cell carcinoma of the liver (PCCCL). Methods: A total of 470 patients with hepatocellular carcinoma were retrospectively analyzed. Multivariate Cox analysis was used to identify potential factors associated with prognosis of PCCCL. Results: Patients with PCCCL showed significantly higher disease-free survival (DFS) and overall survival (OS) compared with patients with non-clear cell hepatocellular carcinoma. Multivariate analysis revealed that AFP level, tumor size, liver cirrhosis and portal vein tumor thrombosis were risk factors for DFS. Tumor size, capsule formation and Ki-67 were risk factors for OS. Satellite nodules acted as a protective factor for DFS and OS. Conclusion: PCCCL is associated with better prognosis in hepatocellular carcinoma. Tumor size and satellite nodules may be independent predictors of OS and DFS.

Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p.

BACKGROUND: Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. METHODS: Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. RESULTS: Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. CONCLUSIONS: Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis.

BACKGROUND: Increased long noncoding RNA (lncRNA) expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms. The present study aimed to identify the mechanism underlying modulation of HCC development by the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). METHODS: Quantitative real-time polymerase chain reaction was used to determine MALAT1 and microRNA (miR)-146a expression in HCC tissues and cell lines. Western blotting was performed to measure PI3K, Akt, and mTOR levels. Dual-luciferase reporter assay was used to validate the direct targeting and negative regulatory interaction between miR-146a and MALAT1. Cell viability, proliferation, and apoptosis were analyzed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, and flow cytometry, respectively; autophagy was detected based on LC3B expression. RESULTS: MALAT1 expression was higher in HCC tissues than in normal tissues. MALAT1 upregulation promoted HCC cell proliferation, whereas MALAT1 downregulation promoted HCC apoptosis and autophagy. Moreover, effects of MALAT1 downregulation on HCC cells were abolished by miR-146a inhibition. miR-146a directly targeted the 3'-untranslated region of PI3K, and PI3K protein level was clearly decreased upon miR-146a mimic transfection. CONCLUSIONS: MALAT1 may modulate HCC cell proliferation, apoptosis, and autophagy via sponging miR-146a, which regulates HCC progression.

c-Myc-mediated SNRPB upregulation functions as an oncogene in hepatocellular carcinoma.

Dysregulation of genes involved in alternative splicing contributes to hepatocarcinogenesis. SNRPB, a component of spliceosome, is implicated in human cancers, yet its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. Here, we show that SNRPB expression is increased in HCC tissues, compared with the nontumorous tissues, at both messenger RNA and protein levels in two independent cohorts. High expression of SNRPB is significantly associated with higher pathological grade, vascular invasion, serum alpha-fetoprotein level, tumor metastasis, and poor disease-free and overall survivals. Luciferase reporter and chromatin immunoprecipitation assays demonstrate that SNRPB upregulation in HCC is mediated by c-Myc. Positive correlation is found between SNRPB and c-Myc expression in clinical samples. In vitro studies show that ectopic expression of SNRPB promotes HCC cell proliferation and migration, whereas knockdown of SNRPB results in the opposite phenotypes. Collectively, our data suggest SNRPB function as an oncogene and serve as a potential prognostic factor in HCC.

The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma.

BACKGROUND: Sorafenib and transarterial chemoembolization (TACE) are recommended therapies for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. METHODS: Between August 2004 and November 2014, 104 patients with BCLC stage B/C HCC were enrolled at the Affiliated Tumor Hospital of Guangxi Medical University, China. Forty-eight patients were treated with sorafenib alone (sorafenib group) and 56 with TACE plus sorafenib (TACE + sorafenib group). Baseline demographic/clinical data were collected. The primary outcomes were median overall survival (OS) and progression-free survival (PFS). Secondary outcomes were overall response rate (ORR) and sorafenib-related adverse events (AEs). Baseline characteristics associated with disease prognosis were identified using multivariate Cox hazards regression. RESULTS: The mean age of the 104 patients (94 males; 90.38%) was 49.02 ± 12.29 years. Of the baseline data, only albumin level (P = 0.028) and Child-Pugh class (P = 0.017) differed significantly between groups. Median OS did not differ significantly between the sorafenib and TACE + sorafenib groups (18.0 vs. 22.0 months, P = 0.223). Median PFS was significantly shorter in the sorafenib group than that in the TACE + sorafenib group (6.0 vs. 8.0 months, P = 0.004). Six months after treatments, the ORRs were similar between the sorafenib and TACE + sorafenib groups (12.50% vs. 18.75%, P = 0.425). The rates of grade III-IV adverse events in sorafenib and TACE + sorafenib groups were 29.2% vs. 23.2%, respectively. TACE plus sorafenib treatment (HR = 0.498, 95% CI = 0.278-0.892), no vascular invasion (HR = 0.354, 95% CI = 0.183-0.685) and Child-Pugh class A (HR = 0.308, 95% CI = 0.141-0.674) were significantly associated with better OS, while a larger tumor number was predictive of poorer OS (HR = 1.286, 95% CI = 1.031-1.604). TACE plus sorafenib treatment (HR = 0.461, 95% CI = 0.273-0.780) and no vascular invasion (HR = 0.557, 95% CI = 0.314-0.988) were significantly associated with better PFS. CONCLUSIONS: Compared with sorafenib alone, combining TACE with sorafenib might prolong survival and delay disease progression in patients with advanced HCC.

miR-290 contributes to the low abundance of cyclin D1 protein in mouse embryonic stem cells.

Mouse miR-290 cluster miRNAs are expressed specifically in early embryos and embryonic germ cells. These miRNAs play critical roles in the maintenance of pluripotency and self-renewal. Here, we showed that Cyclin D1 is a direct target gene of miR-290 cluster miRNAs. Negative relationships between the expression of Cyclin D1 protein and miR-290 cluster miRNAs in pluripotent and non-pluripotent cells, as well as in differentiating CGR8 cells were observed. Inhibition of miR-290 cluster miRNAs could arrest cells at the G1 phase and slow down the cell proliferation in CGR8 mouse stem cells. Since miR-290 cluster miRNAs are the most dominant stem-cell-specific miRNAs, our results revealed an important cause for the absence of Cyclin D1 in mouse embryonic stem cells.

Comparative efficacy of postoperative transarterial chemoembolization with or without antiviral therapy for hepatitis B virus-related hepatocellular carcinoma.

This study aims to investigate the efficacy of adjuvant transarterial chemoembolization (TACE) with or without antiviral therapy for patients with hepatocellular carcinoma (HCC) after radical hepatectomy. This retrospective study examined 176 patients after radical hepatectomy, 118 of whom were treated using TACE alone and 58 using TACE combined with antiviral therapy. To reduce confounding bias due to baseline differences, propensity score matching was used to generate 51 pairs of patients from both treatment groups. Overall survival (OS) and disease-free survival (DFS) were analyzed for both groups before and after propensity score matching. Analysis of all patients showed that OS was better in the combination therapy group than in the TACE-only group (P = 0.048), while DFS was similar between the two groups (P = 0.322). Analysis of only propensity score-matched pairs confirmed the significantly better 5-year OS in the combination therapy group (64.6 vs. 37.5 %, P = 0.033) and also suggested better 5-year DFS (37.9 vs. 14.6 %, P = 0.048). Among patients experiencing HCC recurrence, radical surgery was the treatment choice for a significantly larger proportion of patients from the combination therapy group than from the TACE-only group (P = 0.018). Our results suggest that combining antiviral therapy with TACE significantly improves OS and potentially DFS relative to TACE alone in patients with HCC. Combination therapy also appears to leave patients with greater remnant liver function, increasing the possibility of curative resection in the event of recurrence. Combination therapy may be useful for preventing HCC recurrence after radical hepatectomy.

Postoperative hepatitis B virus reactivation and surgery-induced immunosuppression in patients with hepatitis B-related hepatocellular carcinoma.

BACKGROUND: Hepatectomy in hepatocellular carcinoma (HCC) patients lead to postoperative hepatitis B virus (HBV) reactivation (PHR) as well as immunosuppression. METHODS: This prospective study involved 135 HBV-related HCC patients and 42 control hepatic hemangioma patients. RESULTS: Among HCC patients, 26 (19.3%) suffered PHR. Risk factors for PHR were HBV-cAg S1 positivity [hazard ratio (HR) = 404.82, P = 0.004], high preoperative total bilirubin level (HR = 186.38, P = 0.036), small preoperative proportions of CD3-CD16 + CD56 + cells (HR = 0.01, P = 0.014) and CD19 + B cells (HR = 0.02, P = 0.016), blood transfusion (HR = 157.03, P = 0.006) and high liver cirrhosis S score (HR = 270.45, P = 0.004). On postoperative day (POD) 3, PHR patients showed much greater immunosuppression than non-PHR patients based on proportions of T cells (CD3+, CD3 + CD4+, CD3 + CD8+), B cells (CD19+) and on levels of IgG, IgA antibodies, complement proteins C3, and C4. By POD 7, PHR patients had partially recovered but not as quickly as non-PHR patients: PHR patients still showed deficits in T cells (CD3+, CD3 + CD4+), CD3-CD16 + CD56+ cells and in levels of IgM, C3, C4, and C-reactive protein. CONCLUSION: PHR may be associated with resection-induced immunosuppression in patients with HBV-related HCC.

Systematic review comparing the safety and efficacy of conventional and drug-eluting bead transarterial chemoembolization for inoperable hepatocellular carcinoma.

AIM: Conventional transarterial chemoembolization (cTACE) is widely used for treating patients with inoperable hepatocellular carcinoma (HCC). A variation on the technique based on drug-eluting beads (DEB-TACE) has recently entered the clinic, but trials of its safety and efficacy have given conflicting results. This systematic review aimed to gain a current, comprehensive picture of how DEB-TACE compares with cTACE. METHODS: MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database and clinical trial registries were searched through June 2014. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: The analysis included four randomized controlled trials, one uncontrolled prospective study and one prospective case-control study, altogether involving 652 patients. Overall survival benefit was similar between cTACE and DEB-TACE patients (HR = 1.07, 95% CI = 0.82-1.40, P = 0.875). However, DEB-TACE was associated with a significantly higher objective tumor response rate (RR = 1.14, 95% CI = 1.01-1.29, P = 0.03) and a slightly lower incidence of adverse events. CONCLUSION: Though the available evidence suggests that although DEB-TACE is associated with better tumor response and potentially fewer adverse events, it does not provide greater survival benefit than cTACE. These results need to be validated in high-quality trials with large sample size.

MC1R regulates T regulatory cell differentiation through metabolic reprogramming to promote colon cancer.

BACKGROUND: Until 2021, colon cancer was a leading cancer globally. Early detection improves outcomes; however, advanced cases still having poor prognosis. Therefore, an understanding of associated molecular mechanisms is crucial for developing new preventive and therapeutic strategies for colon cancer. METHODS: The TCGA database was analyzed to assess melanocortin 1receptor (MC1R) expression in colon cancer and its link with patient prognosis. Further, models and diverse experimental techniques were employed to investigate the impact of MC1R on colon cancer progression and its underlying mechanism was elucidated. RESULTS: In a follow-up study of clinical patients, the important role of MC1R was identified in the development of colon cancer. First, MC1R was expressed more highly in colon tumor tissues than in adjacent tissues. In addition, MC1R was associated with colon cancer prognosis, and higher expression of MC1R tended to predict a worse prognosis. This conclusion was verified in MC1R-/- mice, which showed a greater resistance to tumor growth than wild-type mice, as expected. Further investigation revealed a significant change in the portion of Tregs in MC1R-/- mice, while the portion of CD4 + and CD8 + T cells remained unchanged. The in vitro experiments revealed a weaker ability of the MC1R-/- T cells to differentiate into Tregs. Previous studies report that the functional integrity of Tregs is interwoven with cellular metabolism. Therefore, MC1R was deduced to regulate the differentiation of Tregs by reprogramming the metabolism. As expected, MC1R-/- T cells exhibited weaker mitochondrial function and a lower aerobic oxidation capacity. Concurrently, the MC1R-/- T cells had stronger limiting effects on colon cancer cells. According to these results, the MC1R inhibitor was hypothesized as a potential therapeutic agent to suppress colon cancer. The results showed that upon MC1R suppression, the tumors in the mice developed more slowly, and the mice survived longer, potentially providing a novel strategy to treat clinical colon cancer. CONCLUSION: By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.

Epidemiological and survival outcomes of neuroendocrine carcinoma of the breast: a SEER data analysis.

Background: Neuroendocrine carcinoma of the breast (NECB) is a rare subtype of breast cancer, comprising only 0.1% to 5% of all breast cancer cases. Despite its rarity, it is important to gain a better understanding of the epidemiological, clinical, and prognostic features of NECB. The purpose of the study was to obtain population-based evaluations of the epidemiological and survival outcomes of NECB. Methods: The data of patients with neuroendocrine carcinoma diagnosed and enrolled between 2000 and 2017 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Descriptive statistical analyses were used to assess the distribution and tumor-related characteristics of these patients. Kaplan-Meier curves and univariate and multivariate Cox proportional risk models were used to analyze variables that might be associated with prognosis. Results: This study included 7,856 patients with neuroendocrine carcinoma. The median age of the patients was 64 years, and most of them were female, White, and diagnosed at ≥60 years old. The most common pathological type was neoplasm. Survival analysis indicated that there were significant differences in age, marital status, registration location, American Joint Committee on Cancer (AJCC) stage, breast subtype, surgery of primary tumor, and no cancer cause surgery patients with NECB. The results also indicated that treatment with surgery, including surgery of primary tumor, surgery combined with radiation, and no cancer cause surgery, were all effective in improving the prognosis compared with not providing surgical treatment. Conclusions: In conclusion, NECB is a very rare lesion for which age, marital status, registration location, and surgery, AJCC stage, breast subtype were found to be independent prognostic factors.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis.

BACKGROUND: Increasing evidence has suggested a strong association of Q223R (rs1137101) and K109R (rs1137100) polymorphisms in leptin receptor (LEPR) gene with susceptibility of breast cancer (BC), but inconsistent results were obtained. To provide a quantitative assessment of this association, a systematic review and meta-analysis was performed. METHODS: A literature search of PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure was collected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 20 case-control studies for Q223R polymorphism and 8 case-control studies for K109R polymorphism were included. Significant association between Q223R polymorphism and BC risk was not found in total, Asian or Caucasian population, but in African population: allelic model, OR = 0.72, 95% CI = 0.60-0.86, p < 0.001; recessive model, OR = 0.67, 95%CI = 0.52-0.87, P = 0.003; dominant model, OR = 1.58, 95% CI = 1.15-2.17, p = 0.004; homozygous model, OR = 0.51, 95% CI = 0.36-0.78, p < 0.001. Significant association between K109R polymorphism and BC risk was not found in total or Caucasian population, but in Asian population: dominant model, OR = 0.24, 95% CI = 0.07-0.84, p = 0.03; heterozygous model, OR = 1.87, 95% CI = 1.07-3.26, p = 0.03. CONCLUSION: The available evidence suggests that Q223R polymorphism may be significantly associated with BC risk in African population. K109R polymorphism may be significantly associated with BC risk in Asian population.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. Methods: The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. Results: A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Conclusion: Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

Involvement of TRPC7-AS1 Expression in Hepatitis B Virus-Related Hepatocellular Carcinoma.

OBJECTIVE: To investigate the expression of transient receptor potential (TRP) superfamily genes, especially TRPC7-AS1 in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). METHODS: Three cancer samples of HBV-related HCC at phase IV and matched paracancerous liver tissues were included in the study. Total RNA was extracted, and differential expression of RNA was screened by high-throughput transcriptome sequencing. The expression of TRPC7-AS1 was detected by quantitative real-time PCR. The N6-adenosyl methylation RNA in MHCC97H, HepG2, and HL-7702 was enriched by coimmunoprecipitation with m6A antibody, and the relative level of N6-adenosyl methylation RNA in TRPC7-AS1 was detected. RESULTS: The expression of TRP family genes in cancer tissues was higher than that in paracancerous liver tissues, including TRPC7-AS1, TRPC4AP, PKD1P6, and PKD1P1. Moreover, the expression level of TRPC7-AS1 in MHCC97H and HepG2 was also significantly higher than that in L02, a normal liver cell. The methylation level of N6-adenosine of TRPC7-AS1 was lower in HepG2 cells than that in L02 cells. CONCLUSION: TRP superfamily genes, especially TRPC7-AS1, were highly expressed in HBV-related HCC. TRPC7-AS1 could be a potential therapeutic target or diagnostic marker for HCC.