A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

Autor: Gao Z; Department of General Surgery, Peking University First Hospital, Beijing, China., Wan Z; Genecast Biotechnology Co., Ltd., Wuxi City, Jiangsu Province, China., Yu P; Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China., Shang Y; Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, China., Zhu G; Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Wuhan, Hubei Province, China., Jiang H; Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, China., Chen Y; Genecast Biotechnology Co., Ltd., Wuxi City, Jiangsu Province, China., Wang S; Genecast Biotechnology Co., Ltd., Wuxi City, Jiangsu Province, China., Lei F; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Huang W; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Zeng Q; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Wang Y; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Rong W; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Hong Y; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Gao Q; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Niu P; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Zhai Z; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., An K; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Ding C; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China., Wang Y; Department of Pathology, Peking University Shougang Hospital, Beijing, China., Gu G; Department of General Surgery, Air Force Medical Center, Chinese People's Liberation Army, Beijing, China., Wang X; Department of General Surgery, Peking University First Hospital, Beijing, China., Meng Q; Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, China., Ye S; Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Wuhan, Hubei Province, China., Liu H; Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, China., Gu J; Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China.; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.; Peking University International Cancer Institute, Beijing, China.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Jan; Vol. 13 (1), pp. e6720. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1002/cam4.6720
Abstrakt: Background: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence.
Methods: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset.
Results: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort.
Conclusions: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.
(© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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