List of TAN-associated genes.

Comprehensive understanding prognostic relevance of distinct tumor microenvironment (TME) remained elusive in colon cancer. In this study, we performed in silico analysis of the stromal components of primary colon cancer, with a focus on the markers of cancer-associated fibroblasts (CAF) and tumor-associated endothelia (TAE), as well as immunological infiltrates like tumor-associated myeloid cells (TAMC) and cytotoxic T lymphocytes (CTL). The relevant CAF-associated genes (CAFG)(representing R index = 0.9 or beyond with SPARC) were selected based on stroma specificity (cancer stroma/epithelia, cS/E = 10 or beyond) and expression amounts, which were largely exhibited negative prognostic impacts. CAFG were partially shared with TAE-associated genes (TAEG)(PLAT, ANXA1, and PTRF) and TAMC-associated genes (TAMCG)(NNMT), but not with CTL-associated genes (CTLG). Intriguingly, CAFG were prognostically subclassified in order of fibrosis (representing COL5A2, COL5A1, and COL12A1) followed by exclusive TAEG and TAMCG. Prognosis was independently stratified by CD8A, a CTL marker, in the context of low expression of the strongest negative prognostic CAFG, COL8A1. CTLG were comprehensively identified as IFNG, B2M, and TLR4, in the group of low S/E, representing good prognosis. Our current in silico analysis of the micro-dissected stromal gene signatures with prognostic relevance clarified comprehensive understanding of clinical features of the TME and provides deep insights of the landscape.目前学界对结直肠癌中不同肿瘤微环境（Tumor Microenvironment, TME）的预后相关性仍缺乏全面清晰的认知。本研究针对原发性结直肠癌的基质组分开展了计算生物学分析，重点聚焦癌相关成纤维细胞（Cancer-Associated Fibroblasts, CAF）、肿瘤相关内皮细胞（Tumor-Associated Endothelia, TAE）的标志物，以及肿瘤相关髓系细胞（Tumor-Associated Myeloid Cells, TAMC）、细胞毒性T淋巴细胞（Cytotoxic T Lymphocytes, CTL）等免疫浸润组分。本研究基于基质特异性（癌基质/上皮比值，即cS/E≥10）与表达水平，筛选出相关的癌相关成纤维细胞相关基因（CAF-Associated Genes, CAFG，其与SPARC的R指数≥0.9），此类基因大多表现出不良预后效应。CAFG与肿瘤相关内皮细胞相关基因（TAE-Associated Genes, TAEG，包含PLAT、ANXA1及PTRF）、肿瘤相关髓系细胞相关基因（TAMC-Associated Genes, TAMCG，包含NNMT）存在部分基因重叠，但与CTL相关基因（CTL-Associated Genes, CTLG）无重叠。值得注意的是，CAFG可按预后特征分为以纤维化相关基因为代表的亚组（包含COL5A2、COL5A1及COL12A1），以及仅与TAEG和TAMCG相关的亚组。在最强不良预后CAFG成员COL8A1低表达的情境下，CTL标志物CD8A可独立对患者预后进行分层。在低S/E基因特征组中，CTL相关基因（CTLG）被全面鉴定为IFNG、B2M及TLR4，该组提示良好预后。本研究针对具有预后相关性的显微切割基质基因特征开展的计算生物学分析，完善了学界对结直肠癌肿瘤微环境临床特征的全面认知，并为其全景图谱提供了深刻见解。