Jun‐li Wang

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

Abstract The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.

Comprehensive analysis of clinical prognosis and biological significance of CNIH4 in cervical cancer

AbstractBackgroundCornichon homolog 4 (CNIH4) belongs to the CNIH family. It functions as an oncogene in many tumors. However, CNIH4's significance in the immune landscape and its predictive potential in cervical cancer (CESC) is unexplored.MethodsCNIH4 levels and its effect on the survival of patients with CESC were evaluated using data retrieved from The Cancer Genome Atlas (TCGA). The oncogenic effect of CNIH4 in CESC was determined using small interfering RNA‐mediated transfected cell lines and tumorigenesis experiments in animal models.ResultsHigher expression of CNIH4 was found in advanced tumor and pathological stages, as well as lymph node metastasis. CNIH4 expression correlated positively with the infiltration of macrophages M2 and resting dendritic cells into the affected tissue. Additionally, functional enrichment of RNA‐sequencing of CNIH4‐knocked down CESC cell lines showed the association of CNIH4 to the PI3K‐Akt signaling pathway. Single‐sample gene set enrichment analysis highlighted several immune pathways that were elevated in the CESC samples with enhanced levels of CNIH4, including Type‐I and Type‐II IFN‐response pathways. The impact of CNIH4 on drug sensitivity was further assessed using the GDSC database. As CNIH4 is linked to the immune landscape in CESC, this study determined a four‐gene risk prediction signature utilizing CNIH4‐related immunomodulators. The risk score quantified from the prediction signature was an independent predictive indicator in CESC. Receiver operating characteristic curve analysis verified the good predictive ability of the four‐gene signature in TCGA‐CESC cohort. Thus, the CNIH4‐related model showed potential as an auxiliary TNM staging system tool.ConclusionCNIH4 may be an effective predictive biomarker for patients with cervical cancer, thus providing new ideas and research directions for CESC.