Background: A hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma. Methods: Lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index. Results: Four genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4 + T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients. Conclusion: The hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.

Background: 5-methylcytosine (5mC) has been reported in the prognosis of a variety of cancers, however, its role in hepatocellular carcinoma (HCC) has not been investigated yet. This study aimed at identifying the molecular subtypes associated with 5mC and establishing a relevant score to predict its prognosis in HCC. Methods: Somatic gene mutation data and gene expression data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on the expression of 5mC regulators, and the molecular features of each subtype were investigated by survival, mutation, gene set variation, and immune cell infiltration analyses. Next, we performed a differentially expressed analysis based on the new subtypes and selected the overlapping genes for further analysis. We undertook univariate Cox analysis to analyze these genes and constructed a prognostic model by lasso regression analysis. Meanwhile, survival and gene set enrichment analyses were used to explore the prognosis and the relevant pathways, respectively. The LIRI cohort from the International Cancer Genome Consortium database was used as a reference to validate the 5mC subtypes and 5mC score. Results: Twenty-one types of 5mC regulators were employed in this study, and three 5mC-associated molecular subtypes were identified. These three subtypes presented significant differences in prognosis, immune cell infiltration, immune checkpoint inhibitors, signaling pathways, and mutational features. Compared with cluster 3, cluster 2 exhibited significantly increased expression of PD-L1, TIM3, Galectin9, CTLA4, and CD80, while PD-L1, TIM3, and CD80 were higher in cluster 2 than in cluster 1. Furthermore, a 5mC-related score, composed of seven genes (SGPP2, SALL4, B3GNT7, ROR1, MYBL2, SLC7A1, and CAND2), was proven to be significantly associated with prognosis. The established subtypes and scores were thus successfully verified by the validated cohort.

Hepatocellular carcinoma (HCC) is one of the most common primary cancers, and its pathogenesis is complicated and difficult to screen. Currently, there is no effective treatment. In traditional Chinese medicine, a large proportion of patients with HCC have been diagnosed with spleen deficiency (SD) syndrome and treated with tonifying traditional Chinese medicine, which has significant clinical efficacy. However, the role and molecular mechanism of SD in HCC remain unclear. In this study, 40 mice were randomly divided into four groups: control, SD, HCC, and SD-HCC groups. The liver cancer model of SD was established by reserpine induction and orthotopic transplantation. The effects of SD on the proliferation, apoptosis, invasion, and metastasis of HCC cells were studied by cell proliferation, cell apoptosis, cell scratch, and transwell assay. We found that compared with the HCC group, the protein expressions of cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), phosphatase and tensin homolog (PTEN), and AKT (also known as protein kinase B or PKB) in the exosomes of the SD-HCC group were upregulated. In addition, the metastases and self-renewal of exosomes in the SD-HCC group were more aggressive than those in the HCC group, which could be partially reversed with the addition of CTLA-4 inhibitors. Further studies showed that in the internal environment of SD, CTLA-4 promoted tumor invasion and metastasis by regulating the PTEN/CD44 pathway. In conclusion, our findings suggest that during SD in the internal environment, exosome CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.

Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D 3 analogue has anti-psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP-based and haplotype-based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over-represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/ rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x 2 = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.

Background: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene mutation and immunotherapy in HCC. Methods: The somatic gene mutation data and gene expression data were retrieved from International Cancer Genome Consortium database and The Cancer Genome Atlas (TCGA) database. The mutational genes were selected by the intersection of three cohorts and further identified using survival analysis and TMB correlation analysis. After the identification of key mutational gene, we explored the correlation between gene mutation and both the immune cell infiltration and immune inhibitors. The signaling pathways associated with gene mutation were confirmed through gene set enrichment analysis. Furthermore, the survival analysis and mutational analysis based on TCGA cohort were performed for the validation of included gene. Conclusion: Our research firstly revealed the underlying association between CTNNB1 mutation and immunotherapy, and we speculated that CTNNB1 mutation may modulate NK cells by affecting CD96. However, more functional experiments should be performed for verification.