Identification of critical radioresistance genes in esophageal squamous cell carcinoma by whole-exome sequencing

Zhiming Chen; Ninghua Yao; Shu Zhang; Yao Song; Qi Shao; Hongmei Gu; Jianbo Ma; Buyou Chen; Hongyu Zhao; Ye Tian

doi:10.21037/atm-20-5196

Identification of critical radioresistance genes in esophageal squamous cell carcinoma by whole-exome sequencing

Ann Transl Med. 2020 Aug;8(16):998. doi: 10.21037/atm-20-5196.

Authors

Zhiming Chen^{1

2}, Ninghua Yao², Shu Zhang³, Yao Song⁴, Qi Shao⁵, Hongmei Gu², Jianbo Ma², Buyou Chen², Hongyu Zhao², Ye Tian¹

Affiliations

¹ Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Radiotherapy & Oncology, Affiliated Hospital of Nantong University, Nantong, China.
³ Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
⁴ Department of Radiation oncology, Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
⁵ Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer due to insufficient actionable molecules. Radiotherapy (RT) plays a vital role in the treatment of ESCC, while radioresistance is a significant challenge to RT and results in locoregional and distant failure.

Methods: Radioresistance is a complex involving confounding factors, and its genetic mechanism is challenging to study. Postoperative recurrence after RT is more likely to be due to genetic causes than recurrence in unoperated patients. Therefore, two independent cohorts of ESCC patients who had received postoperative radiotherapy (PORT) and had opposite prognoses were set up, and whole-exome sequencing (WES) technology was applied. We compared the differences in the mutant spectra between the two groups.

Results: The mutation rate was slightly higher in the relapsed group than in the stable group [average mutation rate, 1.15 vs. 0.73 mutations per megabyte (Mb)], while the mutation types and proportions in the two groups were not significantly different. In particular, three mutated genes (TTN, MUC19, and NPIPA5) and two copy number alterations (CNAs) (1q amplification and 14q deletion) were identified to be associated with poor RT prognosis, while MUC4 was a favorable factor.

Conclusions: These radioresistance biomarkers may supply insight into predicting the radioresponse. Further, these findings offer the first data on the mutational landscape of ESCC radioresistance.

Keywords: Esophageal squamous cell carcinoma (ESCC); radioresistance; whole-exome sequencing.