Huai Qilin, Guo Wei, Han Liankui, Kong Demiao, Zhao Liang, Song Peng, Peng Yue, Gao Shugeng
Department of Graduate School, Zunyi Medical University, Zunyi, China.
Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China.
Transl Cancer Res. 2021 Apr;10(4):1787-1803. doi: 10.21037/tcr-20-3078.
Esophageal cancer (EC) is a highly aggressive malignancy that is classified as esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Infiltrating stromal/immune cells, a major component of the tumor immune microenvironment (TIME), have prognostic significance in various cancers.
In this study we investigated genes and immune factors in the tumor microenvironment (TME) of ESCC and EAC that can serve as prognostic biomarkers. Stromal and immune scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) algorithm based on gene expression profiles of patient-derived tumor tissues in The Cancer Genome Atlas database. The correlation between ESTIMATE scores and survival rates in EC were analyzed. A comparison of high and low stromal/immune score groups revealed multiple differentially expressed genes (DEGs) as candidate prognostic genes; their role in immune-related biological processes was evaluated by functional and protein-protein interaction (PPI) network analyses, and the genes were validated using Gene Expression Omnibus datasets. Additionally, 22 tumor-infiltrating immune cell (TIIC) subsets were analyzed using the CIBERSORT algorithm.
Median stromal score was higher whereas immune score was lower in ESCC than in EAC (both P<0.01). Stromal score was lower in female as compared to male ESCC patients (P<0.05), and was significantly correlated with T stage (P<0.05). In EAC, median immune score was higher in female as compared to male patients (P<0.05) and was correlated with tumor-node-metastasis stage (P<0.05). The identified DEGs were mainly involved in lymphocyte (especially T-lymphocyte) activation and carbohydrate binding. Moreover, the levels of infiltrating resting-stage dendritic cells, CD8+ T cells, naïve B cells, activated mast cells, and resting memory CD4+ T cells were significantly correlated with EC prognosis (P<0.05).
The immune microenvironment of ESCC and EAC are quite different. We have found genes with prognostic value in multiple tumor databases.
食管癌（EC）是一种侵袭性很强的恶性肿瘤，分为食管鳞状细胞癌（ESCC）和食管腺癌（EAC）。浸润性基质/免疫细胞是肿瘤免疫微环境（TIME）的主要组成部分，在各种癌症中具有预后意义。
在本研究中，我们调查了ESCC和EAC肿瘤微环境（TME）中可作为预后生物标志物的基因和免疫因子。基于癌症基因组图谱数据库中患者来源肿瘤组织的基因表达谱，使用恶性肿瘤组织中基质和免疫细胞估计（ESTIMATE）算法计算基质和免疫评分。分析了ESTIMATE评分与EC生存率之间的相关性。高、低基质/免疫评分组的比较揭示了多个差异表达基因（DEG）作为候选预后基因；通过功能和蛋白质-蛋白质相互作用（PPI）网络分析评估它们在免疫相关生物学过程中的作用，并使用基因表达综合数据集对这些基因进行验证。此外，使用CIBERSORT算法分析了22个肿瘤浸润免疫细胞（TIIC）亚群。
ESCC的基质评分中位数高于EAC，而免疫评分低于EAC（均P<0.01）。女性ESCC患者的基质评分低于男性（P<0.05），且与T分期显著相关（P<0.05）。在EAC中，女性患者的免疫评分中位数高于男性（P<0.05），且与肿瘤-淋巴结-转移分期相关（P<0.05）。鉴定出的DEG主要参与淋巴细胞（尤其是T淋巴细胞）活化和碳水化合物结合。此外，浸润的静止期树突状细胞、CD8+T细胞、幼稚B细胞、活化肥大细胞和静止记忆CD4+T细胞水平与EC预后显著相关（P<0.05）。
ESCC和EAC的免疫微环境有很大差异。我们在多个肿瘤数据库中发现了具有预后价值的基因。
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