Abstract：
Solute carrier family 12 member 8 (SLC12A8) is a nicotinamide mononucleotide transporter. Despite emerging evidence supporting its potential involvement in oncogenesis, a systematic pan-cancer analysis of SLC12A8 has not been performed. Thus, this research aimed to explore the prognostic implications of SLC12A8 and assess its possible immune-related functions across 33 different tumor types. And multiple datasets were retrieved from the databases of TCGA, GTEx, Broad Institute CCLE, TISCH, HPA, and GDSC2. After this data acquisition, bioinformatics analyses were conducted to assess the potential involvement of SLC12A8 in cancer pathogenesis. These analyses focused on examining the relationship between SLC12A8 and prognosis, drug sensitivity, chemotherapy response, immune checkpoints (ICPs), immune cell infiltration, and immunotherapy efficacy across various tumor types. Furthermore, experimental methods such as EdU assay, wound healing assay, and transwell assay were conducted to evaluate the cell proliferative and invasive abilities. Finally, the data analysis demonstrated that SLC12A8 was differentially expressed and predicted unfavorable survival outcomes in the majority of the tumor types in the TCGA dataset. Furthermore, a notable upregulation in the expression of SLC12A8 mRNA and protein was observed in cancer tissues compared to normal tissues. Additionally, the SLC12A8 levels demonstrated a strong association with ICPs, chemokines, immune-activating genes, immune-suppressive genes, chemokine receptors, chemotherapy response, and immunotherapy efficacy. In vitro experiments substantiated that knockdown of SLC12A8 restricted the malignant phenotypes of MDA-MB-231 and BT-549 cells. So SLC12A8 holds promise as a cancer biomarker with the capacity to interact with other ICPs to synergistically regulate the immune microenvironment. Thus, the identification of SLC12A8 contributes to the development of novel therapeutic strategies for enhancing the efficacy of immunotherapy.
摘要：
溶质载体家族12成员8(SLC12A8)是烟酰胺单核苷酸转运蛋白。尽管有新的证据支持它可能参与肿瘤发生，尚未对SLC12A8进行系统的全癌分析.因此，本研究旨在探讨SLC12A8在33种不同肿瘤类型中的预后意义,并评估其可能的免疫相关功能.从TCGA的数据库中检索到多个数据集，GTEx,BroadInstituteCCLE,TISCH,HPA,GDSC2。在这个数据采集之后,进行了生物信息学分析,以评估SLC12A8在癌症发病机制中的潜在参与.这些分析侧重于检查SLC12A8与预后之间的关系，药物敏感性,化疗反应，免疫检查点(ICPs)，免疫细胞浸润，以及各种肿瘤类型的免疫治疗效果。此外，实验方法，如EdU测定，伤口愈合试验，并进行transwell实验以评估细胞增殖和侵袭能力。最后,数据分析表明,SLC12A8在TCGA数据集中的大多数肿瘤类型中有差异表达,并预测了不利的生存结局.此外，与正常组织相比，在癌组织中观察到SLC12A8mRNA和蛋白的表达显着上调。此外,SLC12A8水平与ICP有很强的关联，趋化因子,免疫激活基因，免疫抑制基因，趋化因子受体，化疗反应，和免疫治疗效果。体外实验证实SLC12A8的敲低限制了MDA-MB-231和BT-549细胞的恶性表型。因此，SLC12A8有望成为癌症生物标志物，具有与其他ICP相互作用以协同调节免疫微环境的能力。因此，SLC12A8的鉴定有助于开发新的治疗策略,以提高免疫治疗的疗效.
