N7-methylguanosine-related miRNAs predict hepatocellular carcinoma prognosis and immune therapy.

N7-methylguanosine (m7G) modification has been notably linked with the development of many tumors. However, no investigations have been conducted on whether m7G-related miRNA (m7G-miRNA) is a prognostic index of hepatocellular carcinoma (HCC). Therefore, this investigation aimed to establish a predictive m7G-miRNA signature for efficient HCC prognosis and elucidate the associated immune cell infiltration (ICI) and functions in the tumor microenvironment. RNA sequencing and clinical data on 375 HCC and 50 healthy tissue samples were acquired from The Cancer Genome Atlas database. The m7G-miRNA regulators methyltransferase-like 1 and WD repeat domain 4 were acquired from the TargetScan database. Univariate Cox regression analysis was conducted on the 63 differentially expressed m7G-miRNAs identified. A prognostic signature that consisted of seven miRNAs was identified. According to their risk scores, individuals with HCC were divided into high-risk (HR) and low-risk (LR) cohorts. A Kaplan-Meier test revealed that survival in the HR HCC patients was poorer than in the LR cohort (p < 0.001). The area under the receiver operating characteristic curves of 1-, 3-, and 5-year overall survival were 0.706, 0.695, and 0.715, respectively. A nomogram of sex, risk score, age, and stage indicated the HCC patients' overall survival. Furthermore, it was indicated that the HR and LR patients had different degrees of ICI and immune function. A pathway enrichment analysis revealed the association of several immunity-linked pathways with the risk model. In conclusion, the signature established has great prognostic value and could be used as a new immunotherapy target for individuals with HCC.

Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population.

OBJECTIVE: Mutations in the NLRP3gene have previously been linked to certain forms of cancer, but there have not been any specific studies examining the association between NLRP3 polymorphisms and cervical cancer (CC). This study was therefore designed to investigate the effect of NLRP3 gene polymorphisms on HPV infection and cervical cancer in southern Chinese population. METHODS: Multiplex PCR and next-generation sequencing approaches were used to assess the NLRP3 rs10754558 and rs10733113 polymorphisms in 404 cervical lesion patients, including 227 diagnosed with CC and 177 diagnosed with cervical intraepithelial neoplasia(CIN), with 419 healthy female controls being included for comparison. Correlations between the rs10754558 and rs10733113 genotypes and alleles in these patients and CC and CIN were then analyzed. RESULTS: No correlations were found between NLRP3 rs10754558 and rs10733113 and human papillomavirus(HPV) infection status. Relative to the healthy control group, the NLRP3 rs10754558 GG genotype, CG + GG genotype, and G allele frequencies were significantly increased among patients with cervical lesions (CC and CIN) (OR = 1.815,P = 0.013;OR = 1.383, P = 0.026; OR = 1.284, P = 0.014,respectively), whereas no such differences were observed for rs10733113. A higher cervical lesion risk was detected for patients over the age of 45 exhibiting the rs10754558 GG genotype (OR = 1.848, P = 0.040). Additionally, the risk of CC was elevated in patients with the rs10754558 GG genotype or the G allele relative to patients with the CC genotype or the C allele(OR = 1.830, P = 0.029; OR = 1.281, P = 0.039). The rs10733113 genotypes or alleles were not significantly associated with CC risk (P > 0.05). No association between rs10754558 and rs10733113 genotypes and CC patient clinicopathological features were observed (P > 0.05). Serum NLRP3, IL-1ß, and IL-18 levels were significantly elevated in CC patients relative to healthy controls(P < 0.05). Relative to the CC genotype, CC patients harboring the rs10754558 GG genotype exhibited significantly elevated IL-1ß and IL-18 levels(P < 0.05). CONCLUSION: The rs10754558 polymorphism in the NLRP3 gene may contribute to an elevated risk of CC, although it is not significantly correlated with HPV infection and CC progression.