- Gastrointestinal cancer
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Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer
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Huan Peng, Jun Ying, Jia Zang, Hao Lu, Xiaokai Zhao, Pengmin Yang, Xintao Wang, Jieyi Li, Ziying Gong, Daoyun Zhang, Zhiguo Wang
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Cancer Res Treat. 2023;55(4):1270-1280. Published online April 24, 2023
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DOI: https://doi.org/10.4143/crt.2023.415
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 Abstract
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- Purpose
Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC.
Materials and Methods
Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed.
Results
APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations.
Conclusion
APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.
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Citations
Citations to this article as recorded by  - Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies
Neelakanta Sarvashiva Kiran, Chandrashekar Yashaswini, Rahul Maheshwari, Sankha Bhattacharya, Bhupendra G. Prajapati
ACS Pharmacology & Translational Science.2024; 7(4): 967. CrossRef - Clinical implications of PD-L1 expression and pathway-related molecular subtypes in advanced Asian colorectal cancer patients
Qingqing Qiu
American Journal of Cancer Research.2024; 14(2): 796. CrossRef - Mechanism of APC truncation involved in colorectal cancer tumorigenesis (Review)
Tuya Wang, Jing Fu, Ye Huang, Chun Fu
Oncology Letters.2024;[Epub] CrossRef
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