Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China; Department of Pharmacology, Faculty of Pharmacy, University of Gezira, Wad Madani 20, Sudan.
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China.
Int Immunopharmacol. 2021 Nov;100:108168. doi: 10.1016/j.intimp.2021.108168. Epub 2021 Sep 22.
An in-depth investigation of the molecular and immunologic properties of colorectal adenoma is important for understanding the mechanisms of colorectal cancer (CRC) initiation and development through the adenoma pathway. We performed a meta-analysis of the gene expression data from seven CRC and colorectal sporadic conventional adenoma datasets. We compared the enrichment levels of immune signatures between adenoma, normal colon, and CRC, then applied immunohistochemistry to compare the CD3 + and CD8 + T cells infiltration using samples of adenoma, contiguous adenoma, and CRC. We identified differentially expressed genes (DEGs) between adenoma, normal colon, and CRC, then performed pathway, network, immune correlation, and survival analyses on the DEGs. Adenoma had lower enrichment levels of antitumor immune signatures (CD8 + T cells, NK cells, and MHC Class I) while higher levels of TGF-β and Th17 signatures. Immunohistochemistry revealed variations in CD3 + and CD8 + T cells infiltration between low-grade and high-grade adenomas and between adenoma, normal colon, and CRC. We identified two groups of genes, which we named (NACupGs and NACdownGs), with consistent expression elevation and reduction respectively across the normal, precancerous, and cancerous stages. 48% of the NACupGs had expression levels highly correlated with Treg and TGF-β immune signatures, of which 39% were inversely correlated with CRC survival. We conclude that anti-tumor immune response is reduced at the precancerous (adenoma) stage which is characterized by prominent TGF-β and Th17 activity. The alterations of molecular and immunological profiles in adenoma can provide new insights into the initiation and development of CRC.
深入研究结直肠腺瘤的分子和免疫特性对于通过腺瘤途径理解结直肠癌（CRC）发生和发展的机制非常重要。我们对来自七个 CRC 和结直肠散发性常规腺瘤数据集的基因表达数据进行了荟萃分析。我们比较了腺瘤、正常结肠和 CRC 之间免疫特征的富集水平，然后应用免疫组织化学比较了使用腺瘤、连续腺瘤和 CRC 样本的 CD3+和 CD8+T 细胞浸润。我们鉴定了腺瘤、正常结肠和 CRC 之间差异表达的基因（DEGs），然后对 DEGs 进行了通路、网络、免疫相关性和生存分析。腺瘤具有较低的抗肿瘤免疫特征（CD8+T 细胞、NK 细胞和 MHC 类 I）的富集水平，而 TGF-β和 Th17 特征水平较高。免疫组织化学显示了低级别和高级别腺瘤以及腺瘤、正常结肠和 CRC 之间 CD3+和 CD8+T 细胞浸润的变化。我们鉴定了两组基因，我们分别将其命名为（NACupGs 和 NACdownGs），它们在正常、癌前和癌症阶段均表现出一致的表达升高和降低。NACupGs 的 48%具有与 Treg 和 TGF-β免疫特征高度相关的表达水平，其中 39%与 CRC 生存呈负相关。我们得出结论，在癌前（腺瘤）阶段抗肿瘤免疫反应降低，其特征是 TGF-β 和 Th17 活性明显。腺瘤中分子和免疫特征的改变可以为 CRC 的发生和发展提供新的见解。
