Programmed death-1 and its ligand-1 (PD-1/PD-L1), immune checkpoints proteins, play a crucial role in anti-tumor responses. A large number of studies have evaluated the relationships of PD-1/PD-L1 polymorphisms with risk of cancer, but evidence for the associations remains inconsistent. Therefore, we performed a meta-analysis to examine the associations between PD-1/PD-L1 single nucleotide polymorphisms (SNPs) and cancer predisposition. Results showed that PD-1.3 and PD-L1 rs17718883 were significantly correlated with overall cancer risk. PD-1.5 was prominently linked with cervical cancer (CC), non-small cell lung cancer (NSCLC), TC (thyroid cancer), brain tumor, AML (acute myelocytic leukemia) and UCC (urothelial cell carcinoma) risk, PD-1.9 with breast cancer (BC), AML, esophageal cancer (EC) and ovarian cancer (OC) risk, and PD-1.3 with colorectal cancer (CRC) and BCC (basal cell carcinoma) risk. PD-1.1 polymorphism slightly elevated BC and OC susceptibility, whereas the rs4143815 variant notably decreased the risk of gastric cancer (GC), hepatocellular carcinoma (HCC) and OC, but increased the risk of BC. PD-1.6 was closely linked with AML risk, PD-L1 rs2890658 with NSCLC, HCC and BC risk, rs17718883 with HCC and GC risk, rs10815225 with GC risk, and rs2297136 with NSCLC and HCC risk. Interestingly, the rs7421861, rs10815225, and rs10815225 markedly reduced cancer susceptibility among Asians. The rs7421861 polymrophism decreased cancer risk among Caucasians, rather than the rs10815225 elevated cancer risk. Our results supported that PD-1 and PD-L1 SNPs were dramatically correlated with cancer risk.
Abstract Background Recent years have witnessed the emergence of Cell Division Cycle Associated 7 (CDCA7) as a participant in the genesis of diverse tumors. Despite this, comprehensive pan-cancer evaluations of CDCA7 remain scarce. Consequently, this study aims to rectify this gap by scrutinizing the potential implications of CDCA7 in pan-cancers. Methods We first assessed the expression levels of CDCA7 in 33 cancers and the association of its expression with tumor pathological stage using TCGA, GTEx, GEPIA2, TIMER2.0, TISIDB, UALCAN, and StarBase. Then, prognostic assessment was performed using GEPIA2 and Kaplan-Meier plotter. Gene alterations of CDCA7 were analyzed using cBioPortal, and renal clear cell carcinoma cells lines were screened to determine the function of CDCA7. Finally, we performed tumor immune infiltration analysis using TIMER2.0 and enrichment analysis of CDCA7 by STRING, GEPIA2, and DAVID. The role of CDCA7 in renal clear cell carcinoma (cc) was verified by qPCR, CCK8, wound healing, transwell and cell cycle assay. Results Our study demonstrated that CDCA7 exhibited notable expression across various cancers, and its heightened expression correlated with an unfavorable prognosis for tumor patients. Correlations emerged between CDCA7 expression and the presence of tumor-infiltrating immune cells (TIICs). Moreover, CDCA7 upregulation corresponded to CD8 + T cell infiltration in some tumors. Most malignancies demonstrated a positive relationship between CDCA7 and cancer-associated fibroblast infiltration. Enrichment studies unveiled CDCA7's involvement in cell cycle and DNA metabolism, in addition to its role in multiple signaling pathways that drive tumor progression. Experimental validations underscored CDCA7's role in stimulating the progression of renal clear cell carcinoma. Insights from CCK8 and cell cycle assays confirmed that CDCA7 inhibition attenuated cellular activity and curtailed proliferative capacity in 769-P cells. Wound healing and Transwell assays substantiated that CDCA7 blockade significantly reduced migration and invasion capabilities of 769-P cells. Additionally, quantitative PCR results corroborated the efficacy of CDCA7 inhibition in preventing the epithelial-mesenchymal transition state of renal clear cell carcinoma. Conclusions In conclusion, the comprehensive pan-cancer investigation imparts intricate insights into the engagement of CDCA7 in carcinogenesis. Our findings indicate that CDCA7 holds the potential to serve as a valuable prognostic marker and an alluring target for therapeutic interventions, thereby unveiling novel avenues for future research.
Abstract Background Numerous studies have demonstrated long noncoding RNA (lncRNA) play an important role in the occurrence and progression of cancer, and single nucleotide polymorphisms (SNPs) located in lncRNA are considered to affect cancer suspensibility. Herein, a meta-analysis was carried out to better assess the relationship of H19 polymorphisms and cancer susceptibility. Methods A literature search was conducted through using PubMed, EMBASE, and Web of Science databases to obtain relevant publications before Aug 23, 2022. The reference lists of the retrieved studies were also investigated to identify additional relevant articles. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to appraise the risk of various cancers. Results There appeared to be a remarkable correlation between the rs2107425 variation and decreased cancer risk among Caucasians. Nevertheless, the rs217727 polymorphism was significantly associated with an increased risk of lung cancer, hepatocellular carcinoma and oral squamous cell carcinoma. Also, we found a significant correlation between the rs2839698 polymorphism and increased cancer risk among Asians, gastric cancer, hepatocellular carcinoma, hospital-based control and larger simple size subgroups, respectively. Similarly, the rs3741219 mutation was notably related to cancer risk in higher quality score. As for rs3024270 polymorphism, the homozygous model was markedly linked to cancer risk in overall analysis and population-based controls. There was no significant association between the rs3741216 polymorphism and cancer risk. Conclusion H19 rs2839698 and rs3024270 were closely associated with overall cancer risk. H19 rs2107425 was related to lower cancer risk among Caucasians, while the rs2839698 was related to increased cancer risk among Asians. Our results supported that H19 SNPs were significantly correlated with cancer risk.
Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data.
Triple-negative breast cancer (TNBC) is highly aggressive and does not express estrogen receptor (ER), progesterone (PR), or human epidermal growth factor receptor 2 (HER2). It has a poor prognosis, and traditional endocrine and anti-HER2 targeted therapies have low efficacy against it. In contrast, surgery, radiotherapy, and/or systemic chemotherapy are relatively effective at controlling TNBC. The resistance of TNBC to currently available clinical therapies has had a significantly negative impact on its treatment outcomes. Hence, new therapeutic options are urgently required. Chimeric antigen receptor T cell (CAR-T) therapy is a type of immunotherapy that integrates the antigen specificity of antibodies and the tumor-killing effect of T cells. CAR-T therapy has demonstrated excellent clinical efficacy against hematological cancers. However, its efficacy against solid tumors such as TNBC is inadequate. The present review aimed to investigate various aspects of CAR-T administration as TNBC therapy. We summarized the potential therapeutic targets of CAR-T that were identified in preclinical studies and clinical trials on TNBC. We addressed the limitations of using CAR-T in the treatment of TNBC in particular and solid tumors in general and explored key strategies to overcome these impediments. Finally, we comprehensively examined the advancement of CAR-T immunotherapy as well as countermeasures that could improve its efficacy as a TNBC treatment and the prognosis of patients with this type of cancer.
Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer’s disease (AD), Parkinson’s disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms ( Fok I, Bsm I, Taq I, and Apa I) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the Apa I polymorphism decreased the overall AD risk, and the Taq I increased the overall PD susceptibility. In addition, the Bsm I and Apa I polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the Taq I and Apa I genotypes reduced the AD predisposition among Caucasians, while the Taq I polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the Apa I variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility.
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