The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Guangdong, China.
Institute of Oncologic Pathology, Shantou University Medical College, Shantou, China.
J Immunol Res. 2021 Feb 10;2021:5964752. doi: 10.1155/2021/5964752. eCollection 2021.
Colorectal cancer (CRC) has two major subtypes, microsatellite instability (MSI) and microsatellite stability (MSS) based on the genomic instability. In this study, using computational programs, we identified 9 master transcription factors (TFs) based on epigenomic profiling in MSS CRC samples. Notably, unbiased gene set enrichment analysis (GSEA) showed that several master TFs were strongly associated with immune-related functions in TCGA MSS CRC tissues, such as interferon gamma (IFN-) and interferon alpha (IFN-) responses. Focusing to the top candidate, ASCL2, we found that CD8 T cell infiltration was low in ASCL2 overexpressed MSS CRC samples. Compared with other gastrointestinal (GI) cancers (gastric cancer, MSI CRC, and esophageal cancer), ASCL2 is specifically upregulated in MSS CRC. Moreover, we identified 28 candidate genes in IFN- and IFN- response pathways which were negatively correlated with ASCL2. Together, these results link transcriptional dysregulation with the immune evasion in MSS CRC, which may advance the understanding of immune resistance and contribute to developing novel treatments of MSS CRC.
结直肠癌（CRC）有两种主要亚型，基于基因组不稳定性的微卫星不稳定（MSI）和微卫星稳定（MSS）。在这项研究中，我们使用计算程序，根据 MSS CRC 样本的表观基因组图谱鉴定了 9 个主要转录因子（TF）。值得注意的是，无偏基因集富集分析（GSEA）显示，几个主要 TF 与 TCGA MSS CRC 组织中的免疫相关功能密切相关，如干扰素γ（IFN-）和干扰素α（IFN-）反应。针对顶级候选物 ASCL2，我们发现 ASCL2 过表达 MSS CRC 样本中的 CD8 T 细胞浸润水平较低。与其他胃肠道（GI）癌症（胃癌、MSI CRC 和食管癌）相比，ASCL2 在 MSS CRC 中特异性上调。此外，我们在 IFN- 和 IFN- 反应途径中鉴定了 28 个与 ASCL2 呈负相关的候选基因。总之，这些结果将转录失调与 MSS CRC 的免疫逃逸联系起来，这可能有助于深入了解免疫抵抗，并为开发 MSS CRC 的新治疗方法做出贡献。
