Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma.
Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma.
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与早期肺腺癌肿瘤浸润淋巴细胞相关的预后自噬相关基因对指数的开发和验证
DOI：
10.3389/fcell.2021.719011
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Wang ZH;Li Y;Zhang P;Xiang X;Wei XS;Niu YR;Ye LL;Peng WB;Zhang SY;Xue QQ;Zhou Q
自噬在肺癌中的作用是上下文相关的，也是复杂的。最近的研究报道了自噬在肿瘤免疫逃逸中的重要作用。然而，早期肺腺癌(LUAD)自噬与肿瘤浸润性淋巴细胞(TIL)之间的关系尚不清楚。在这项研究中，我们旨在建立和验证多个LUAD队列中的自噬相关基因对指数(ATGPI)和自噬临床预后指数(ACPI)，这些队列包括癌症基因组图谱(TCGA)队列、基因表达总括队列和武汉协和医院(UH)队列中的一个队列，使用具有最小绝对收缩和选择算子的Cox比例风险回归模型。多因素COX回归分析显示，ATGPI值高的患者和低ATGPI值的患者在检验[风险比(HR)=1.97；P&t；0.001]和TCGA验证(HR=2.25；P<；0.001)队列中的总生存率(OS)有显著差异。还进行了随时间变化的接收器工作特性曲线分析。我们发现，高ATGPI可以准确地识别OS较短的早期LUAD患者，在测试和TCGA验证队列中，曲线下面积分别为0.703和0.676。采用一致性指数(C-index)评价ATGPI和ACPI的有效性。ACPI的C指数在测试(0.71vs.0.66；P<；0.001)、TCGA验证(0.69vs.0.65；P=0.028)和UH(0.80vs.0.70；P=0.015)队列中高于ATGPI。TIL分析显示，在TCGA验证和UH队列中，高ATGPI组的肿瘤浸润性CD4+T细胞比例低于低ATGPI组。这些结果表明，与TIL相关的ATG信号在识别不同OS的早期LUAD患者方面具有潜在的临床应用价值。
The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97;P< 0.001] and TCGA validation (HR = 2.25;P< 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66;P< 0.001), TCGA validation (0.69 vs. 0.65;P= 0.028), and UH (0.80 vs. 0.70;P= 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.
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影响因子：
29
作者：
Kimmelman AC;White E
通讯作者：
White E
DOI：
10.1002/path.5096
发表时间：
2018-08
期刊：
The Journal of pathology
影响因子：
--
作者：
Martínez-Terroba E;Behrens C;de Miguel FJ;Agorreta J;Monsó E;Millares L;Sainz C;Mesa-Guzman M;Pérez-Gracia JL;Lozano MD;Zulueta JJ;Pio R;Wistuba II;Montuenga LM;Pajares MJ
通讯作者：
Pajares MJ
BIM的诱导对于突变体EGFR依赖性肺腺癌中EGFR激酶抑制剂触发的凋亡至关重要。
影响因子：
15.8
作者：
Gong, Yixuan;Somwar, Romel;Politi, Katerina;Balak, Marissa;Chmielecki, Juliann;Jiang, Xuejun;Pao, William
通讯作者：
Pao, William
影响因子：
10.3
作者：
Ajona, Daniel;Pajares, Maria J.;Pio, Ruben
通讯作者：
Pio, Ruben
影响因子：
8
作者：
Liang, M-C;Ma, J.;Chen, L.;Kozlowski, P.;Qin, W.;Li, D.;Goto, J.;Shimamura, T.;Hayes, D. N.;Meyerson, M.;Kwiatkowski, D. J.;Wong, K-K
通讯作者：
Wong, K-K