Multi gene mutation signatures in colorectal cancer patients: predict for the diagnosis, pathological classification, staging and prognosis

BMC Cancer

Yan Zhuang¹  Yuanjing Hu²  Ying Li³  Da Jiang³  Lixia Feng⁴  Hailong Wang⁵  Pengfei Liu⁵  Mingyu Pu⁶  Caijuan Tian⁶  Xiaowei Wang⁷  Jiangyan Zhang⁷ 

[1] Department of Colorectal Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China;Department of Gynecological Oncology, Tianjin Central Hospital of Obstetrics & Gynecology, No. 156 Nankai Third Road, Nankai District, 300100, Tianjin, China;Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, 050000, Shijiazhuang, Hebei, China;Department of Nursing, Tianjin Cancer Hospital Airport Hospital, 300300, Tianjin, China;Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No.354 Beima Road, Hongqiao District, 300120, Tianjin, China;Tianjin Marvel Medical Laboratory, Tianjin Marvelbio Technology Co., Ltd, 300381, Tianjin, China;Tianjin Yunquan Intelligent Technology Co., Ltd, 300381, Tianjin, China;

关键词: Colorectal cancer (CRC);    Genotype;    Pathological classification;    Staging;    Prognosis;   

DOI  :  10.1186/s12885-021-08108-9

来源: Springer

【 摘 要 】

BackgroundIdentifying gene mutation signatures will enable a better understanding for the occurrence and development of colorectal cancer (CRC), and provide some potential biomarkers for clinical practice. Currently, however, there is still few effective biomarkers for early diagnosis and prognostic judgment in CRC patients. The purpose was to identify novel mutation signatures for the diagnosis and prognosis of CRC.MethodsClinical information of 531 CRC patients and their sequencing data were downloaded from TCGA database (training group), and 53 clinical patients were collected and sequenced with targeted next generation sequencing (NGS) technology (validation group). The relationship between the mutation genes and the diagnosis, pathological type, stage and prognosis of CRC were compared to construct signatures for CRC, and then analyzed their relationship with RNA expression, immunocyte infiltration and tumor microenvironment (TME).ResultsMutations of TP53, APC, KRAS, BRAF and ATM covered 97.55% of TCGA population and 83.02% validation patients. Moreover, 57.14% validation samples and 22.06% TCGA samples indicated that patients with mucinous adenocarcinoma tended to have BRAF mutation, but no TP53 mutation. Mutations of TP53, PIK3CA, FAT4, FMN2 and TRRAP had a remarkable difference between I-II and III-IV stage patients (P < 0.0001). Besides, the combination of PIK3CA, LRP1B, FAT4 and ROS1 formed signatures for the prognosis and survival of CRC patients. The mutations of TP53, APC, KRAS, BRAF, ATM, PIK3CA, FAT4, FMN2, TRRAP, LRP1B, and ROS1 formed the signatures for predicting diagnosis and prognosis of CRC. Among them, mutation of TP53, APC, KRAS, BRAF, ATM, PIK3CA, FAT4 and TRRAP significantly reduced their RNA expression level. Stromal score, immune score and ESTIMATE score were lower in patients with TP53, APC, KRAS, PIK3CA mutation compared non-mutation patients. All the 11 gene mutations affected the distributions of immune cells.ConclusionThis study constructed gene mutation signatures for the diagnosis, treatment and prognosis in CRC, and proved that their mutations affected RNA expression levels, TME and immunocyte infiltration. Our results put forward further insights into the genotype of CRC.

【 授权许可】

CC BY