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Abstract：
The most prevalent and insidious type of kidney cancer is kidney clear cell carcinoma (KIRC). Thioredoxin-interacting protein (TXNIP) encodes a thioredoxin-binding protein involved in cellular energy metabolism, redox homeostasis, apoptosis induction and inflammatory responses. However, the relationship between TXNIP, immune infiltration and its prognostic value in KIRC remains unclear. Thus, the present study evaluated the potential for TXNIP as a prognostic marker in patients with KIRC. Data from The Cancer Genome Atlas were used to assess relative mRNA expression levels of TXNIP in different types of cancer. The protein expression levels of TXNIP were evaluated using the Human Protein Atlas. Enrichment analysis of genes co-expressed with TXNIP was performed to assess relevant biological processes that TXNIP may be involved in. CIBERSORT was used to predict the infiltration of 21 tumor-infiltrating immune cells (TIICs). Univariate and multivariate Cox regression analyses were used to assess the relationship between TXNIP expression and prognosis. Single-cell RNA-sequencing datasets were used to evaluate the mRNA expression levels of TXNIP in certain immune cells in KIRC. The CellMiner database was used to analyze the relationship between TXNIP mRNA expression and drug sensitivity in KIRC. The results from the present study demonstrated that TXNIP expression was significantly decreased in KIRC tissue compared with that in normal tissue, as confirmed by western blotting and reverse transcription-quantitative PCR. In addition, downregulated TXNIP expression was significantly associated with poor prognosis, a high histological grade and an advanced stage. The Cell Counting Kit-8 assay demonstrated that TXNIP overexpression significantly suppressed tumor cell proliferation. Univariate and multivariate Cox regression analyses indicated that TXNIP served as a separate prognostic factor in KIRC. Moreover, TXNIP expression was significantly correlated with the accumulation of several TIICs and its overexpression significantly downregulated the mRNA expression levels of CD25 and cytotoxic T-lymphocyte-associated protein 4, immune cell surface markers in CD4+ T lymphocytes. In conclusion, TXNIP may be used as a possible biomarker to assess unfavorable prognostic outcomes and identify immunotherapy targets in KIRC.
摘要：
肾癌的最普遍和最隐蔽的类型是肾透明细胞癌(KIRC)。硫氧还蛋白相互作用蛋白（TXNIP）编码参与细胞能量代谢的硫氧还蛋白结合蛋白，氧化还原稳态，凋亡诱导和炎症反应。然而,TXNIP之间的关系，免疫浸润及其在KIRC中的预后价值尚不清楚。因此，本研究评估了TXNIP作为KIRC患者预后标志物的潜力.来自癌症基因组图谱的数据用于评估不同类型癌症中TXNIP的相对mRNA表达水平。使用人蛋白质图谱评估TXNIP的蛋白质表达水平。进行与TXNIP共表达的基因的富集分析以评估TXNIP可能参与的相关生物学过程。CIBERSORT用于预测21种肿瘤浸润性免疫细胞（TIIC）的浸润。单变量和多变量Cox回归分析用于评估TXNIP表达与预后之间的关系。使用单细胞RNA测序数据集来评估KIRC中某些免疫细胞中TXNIP的mRNA表达水平。使用CellMiner数据库分析KIRC中TXNIPmRNA表达与药物敏感性之间的关系。本研究结果表明，与正常组织相比，TXNIP在KIRC组织中的表达明显降低，通过蛋白质印迹和逆转录定量PCR证实。此外,TXNIP表达下调与不良预后显著相关,组织学分级和晚期。细胞计数试剂盒-8测定证明TXNIP过表达显著抑制肿瘤细胞增殖。单变量和多变量Cox回归分析表明，TXNIP是KIRC的独立预后因素。此外，TXNIP表达与几种TIIC的积累显着相关，其过表达显着下调了CD4T淋巴细胞中CD25和细胞毒性T淋巴细胞相关蛋白4的mRNA表达水平。总之,TXNIP可用作可能的生物标志物，以评估KIRC中的不良预后结果并确定免疫治疗靶标。
