Zhao Lulu, Wang Wanqing, Niu Penghui, Luan Xiaoyi, Zhao Dongbing, Chen Yingtai
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Genet. 2022 Jul 19;13:900124. doi: 10.3389/fgene.2022.900124. eCollection 2022.
Collagen triple helix repeat containing-1 (CTHRC1), highly expressed in multiple human solid tumors, has been identified as a tumor associated protein. However, its specific role and mechanism with immune infiltrates in gastric cancer are still unclear. In this study, we systematically explored and validated the expression and prognostic value of CTHRC1 in gastric cancer by integrating the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Genome Sequence Archive (GSA) datasets. Compared to adjacent normal tissues, we observed that CTHRC1 was highly overexpressed in tumor sample of multiple cancers. It was revealed that CTHRC1 overexpression was positively correlated with the T stage in gastric cancer but not lymph nodes metastasis from TCGA dataset. In addition, CTHRC1 expression may induce tumor associated macrophage infiltration though GRN/TNFRSF1A and AnxA1/FPR1 pathways and also tumor angiogenesis in gastric cancer. In this context, our results indicate that CTHRC1 plays a pivotal role in regulating the angiogenesis and macrophage infiltration in tumor microenvironment, and also can predict poor prognosis in gastric cancer, suggesting that CTHRC1 might be a promising novel immunotherapy and angiogenesis target for gastric cancer.
含胶原蛋白三螺旋重复序列-1（CTHRC1）在多种人类实体瘤中高表达，已被确定为一种肿瘤相关蛋白。然而，其在胃癌中与免疫浸润的具体作用及机制仍不清楚。在本研究中，我们通过整合癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和基因组序列存档库（GSA）数据集，系统地探究并验证了CTHRC1在胃癌中的表达及预后价值。与邻近正常组织相比，我们观察到CTHRC1在多种癌症的肿瘤样本中高度过表达。从TCGA数据集可知，CTHRC1的过表达与胃癌的T分期呈正相关，但与淋巴结转移无关。此外，CTHRC1的表达可能通过GRN/TNFRSF1A和AnxA1/FPR1途径诱导肿瘤相关巨噬细胞浸润，以及胃癌中的肿瘤血管生成。在此背景下，我们的结果表明CTHRC1在调节肿瘤微环境中的血管生成和巨噬细胞浸润方面起关键作用，并且还可预测胃癌的不良预后，提示CTHRC1可能是一种有前景的新型胃癌免疫治疗和血管生成靶点。
