TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma.
TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma.
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TOX 与肺腺癌的预后、免疫浸润和 T 细胞耗竭相关
作者：
Guo L;Li X;Liu R;Chen Y;Ren C;Du S
胸腺细胞选择相关的高迁移率族蛋白（TOX）在先天免疫和肿瘤微环境的发展中起着至关重要的作用。本研究旨在探索TOX的预后潜力，并全面分析TOX，免疫浸润和T细胞功能在各种癌症，特别是肺腺癌（LUAD）中的相关性。TIMER用于分析不同癌症中的TOX表达。通过PrognoScan、Kaplan-Meier绘图仪和GEPIA 2评价TOX的潜在预后价值。用TIMER和GEPIA 2分析TOX、免疫浸润和相关基因标记集之间的关系。分析LUAD中T细胞的单细胞RNA序列，以进一步研究TOX表达与不同T细胞群之间的相关性。TOX在大多数癌症类型中下调，并与LUAD的预后不良相关。TOX对早期、吸烟或低TMB状态的LUAD生存率有显著影响。增加的TOX表达与大多数免疫细胞和功能性T细胞（包括耗尽的T细胞）中的高免疫浸润水平正相关。此外，包括PD-1、TIM-3、TIGHT和CXCL 13的耗竭T细胞的多个关键基因与TOX具有显著的相互作用。具体而言，在LUAD的单细胞RNA-seq分析中，观察到TOX在耗尽的CD 4+和CD 8 + T细胞群中高度富集。TOX是多种癌症类型的预后相关生物标志物，尤其是LUAD。增加的TOX表达显著增加了大多数免疫细胞中的免疫浸润水平，所述免疫细胞包括CD 8 + T细胞、CD 4 + T细胞、肥大细胞和功能性T细胞。此外，我们证实TOX与T细胞耗竭高度相关，并且可能是LUAD中促进T细胞耗竭的关键调节因子。TOX表达的检测可以帮助预测预后，调节疲惫的T细胞中的TOX表达可以为最大限度地提高LUAD的免疫治疗效果提供一种新的策略。在这项研究中，我们发现TOX是多种癌症类型（尤其是肺腺癌）的预后相关生物标志物，并与大多数免疫细胞和功能性T细胞中的免疫浸润水平相关。同时，在单细胞RNA-seq分析中观察到TOX在耗尽的CD 4+和CD 8 + T细胞群体中高度富集。我们的研究结果表明，检测TOX的表达水平可能有助于预测预后，并且调节耗尽的T细胞中的TOX表达可能为肺腺癌患者提供最大化免疫治疗效果的潜在策略。
Thymocyte selection‐associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltration, and T cells function in diverse cancers particularly lung adenocarcinoma (LUAD). TIMER was used to analyze TOX expression in different cancers. Potential prognostic value of TOX was evaluated by the PrognoScan, Kaplan‐Meier Plotter, and GEPIA2. The relationships between TOX, immune infiltration, and related gene marker sets were analyzed by TIMER and GEPIA2. Single‐cell RNA‐seq for T cells in LUAD was analyzed to further investigate the correlations between TOX expression and different T cells populations. TOX downregulates in most of the cancer types and correlates with poor prognosis in LUAD. TOX shows significant impacts on survival of LUAD with early stage, ever‐smoking, or low‐TMB status. Increased TOX expression positively correlates with high immune infiltration levels in most of the immune cells and functional T cells including exhausted T cells. Moreover, multiple key genes of exhausted T cells comprising PD‐1, TIM‐3, TIGHT, and CXCL13 have remarkable interaction with TOX. Specifically, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single‐cell RNA‐seq analysis for LUAD. TOX is a prognosis‐related biomarker for multiple cancer types especially LUAD. Increased TOX expression significantly increase immune infiltration levels in most of the immune cells comprising CD8+ T cells, CD4+ T cells, mast cells, and functional T cells. Moreover, we verified that TOX highly correlates with exhausted T cells and is probable a critical regulator promoted T cells exhaustion in LUAD. Detection of TOX expression could help to predict prognosis and regulating TOX expression in exhausted T cells may offer a novel strategy in maximizing immunotherapy efficacy for LUAD. In this study, we identified TOX is a prognosis‐related biomarker for multiple cancer types especially lung adenocarcinoma and correlate with immune infiltration levels in most of immune cells and functional T cells. Meanwhile, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single‐cell RNA‐seq analysis. Our findings suggested that detecting expression level of TOX may help to predict prognosis and regulating TOX expression in exhausted T cells may provide a potential strategy in maximizing immunotherapy efficacy for lung adenocarcinoma patients.
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