The Novel Tumor Microenvironment-Related Prognostic Gene AIF1 May Influence Immune Infiltrates and is Correlated with TIGIT in Esophageal Cancer
The Novel Tumor Microenvironment-Related Prognostic Gene AIF1 May Influence Immune Infiltrates and is Correlated with TIGIT in Esophageal Cancer
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新的肿瘤微环境相关预后基因 AIF1 可能影响免疫浸润，并与食管癌中的 TIGIT 相关
DOI：
10.1245/s10434-021-10928-9
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Yun Fan
中科院分区：
文献类型：
--
作者：
Xiaoling Xu;Ding Wang;Na Li;Jiamin Sheng;Mingying Xie;Zichao Zhou;Guoping Cheng;Yun Fan
食道癌(EC)是全球第六大常见的癌症相关死亡原因。研究肿瘤微环境(TME)与病理和预后的关系将有助于阐明预测预后的潜在机制，并为免疫治疗食管癌提供新的靶点。使用估计算法计算间质和免疫评分。通过最佳评分截断点确定差异表达基因(Deg)。功能的丰富由David分析，而预后基因的探索使用Kaplan-Meier方法。使用组织芯片中的免疫组织化学方法对145例EC患者的样本进行验证分析。采用多重免疫荧光染色方法检测90例食管癌患者的T细胞免疫受体Ig和ITIM结构域(TIGIT)等6种免疫标志物。结果免疫评分随年龄增长而显著升高，间质评分随肿瘤分期增加而显著升高。包括同种异体移植物炎症因子1(AIF1)在内的15个TME相关基因被确定为EC的预后因素。此外，验证队列表明，AIF1与食管鳞癌患者的预后呈负相关。随后的分析表明，AIF1可能会影响免疫渗透，包括T细胞和自然杀伤细胞。结论TME相关基因AIF1可作为预测食管癌预后的指标，并与食管癌的免疫浸润和TIGIT表达有关。然而，还需要进一步的机制研究。
BackgroundEsophageal carcinoma (EC) is the sixth most common cause of cancer-related mortality worldwide. Studying the associations of the tumor microenvironment (TME) with pathology and prognosis would illustrate the underlying mechanism of prognostic prediction and provide novel targets for immunotherapy in the treatment of EC.MethodsTranscriptomic profiles of 159 EC patients were obtained from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores were calculated using the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified by the optimal score cutoff. Functional enrichments were analyzed by DAVID, while prognostic genes were explored using the Kaplan–Meier method. Validation analysis was performed using immunohistochemistry in tissue microarrays containing samples from 145 EC patients. Multiplex immunofluorescence staining was performed to detect a panel of 6 immune markers, including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), in 90 EC patients.ResultsImmune scores significantly increased with increasing age, while stromal scores were dramatically elevated with increasing tumor stage. Fifteen TME-related DEGs including allograft inflammatory factor 1 (AIF1) were identified as prognostic factors of EC. Furthermore, the validation cohort indicated that AIF1 was negatively associated with the prognosis of esophageal squamous cell carcinoma patients. Subsequent analyses suggested that AIF1 may affect immune infiltrates, including T cells and natural-killer cells. Moreover, a correlation between AIF1 and TIGIT was identified.ConclusionsThese results indicate that the TME-related gene AIF1 is a promising predictor of prognosis and is related to immune infiltrates and TIGIT expression in EC. However, further mechanistic studies are needed.
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影响因子：
3.8
作者：
Anderegg, Martinus C. J.;Ruurda, Jelle P.;Henegouwen, Mark I. van Berge
通讯作者：
Henegouwen, Mark I. van Berge
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
24.5
作者：
Thompson ED;Zahurak M;Murphy A;Cornish T;Cuka N;Abdelfatah E;Yang S;Duncan M;Ahuja N;Taube JM;Anders RA;Kelly RJ
通讯作者：
Kelly RJ
DOI：
10.18632/aging.101415
发表时间：
2018-04-16
期刊：
Aging
影响因子：
--
作者：
Jia D;Li S;Li D;Xue H;Yang D;Liu Y
通讯作者：
Liu Y
影响因子：
4.2
作者：
Yang Ye;Shuhan Miao;Rongzhu Lu;Xiaowei Xia;Yansu Chen;Jianbing Zhang;Xuming Wu;Song He;Fulin Qiang;Jianwei Zhou
通讯作者：
Yang Ye;Shuhan Miao;Rongzhu Lu;Xiaowei Xia;Yansu Chen;Jianbing Zhang;Xuming Wu;Song He;Fulin Qiang;Jianwei Zhou