Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy

Lisi Zeng; Xubo Huang; Yun Tian; Jinxia Huang; Huiyan Liu; Juncai Wen; Kaihua Liu; Yang Shao; Jiali Luo; Hongsheng Tang; Quanxing Liao; Ziying Lei; Weiwen Cui; Qianghua Xia; Tianpei Guan; Jin Li; Shuzhong Cui

doi:10.3389/fonc.2022.796263

Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy

Front Oncol. 2022 Mar 8:12:796263. doi: 10.3389/fonc.2022.796263. eCollection 2022.

Authors

Lisi Zeng¹, Xubo Huang¹, Yun Tian², Jinxia Huang¹, Huiyan Liu¹, Juncai Wen², Kaihua Liu³, Yang Shao³, Jiali Luo¹, Hongsheng Tang², Quanxing Liao², Ziying Lei², Weiwen Cui⁴, Qianghua Xia¹, Tianpei Guan², Jin Li¹, Shuzhong Cui^{2

5}

Affiliations

¹ Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
² Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
³ Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China.
⁴ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, United States.
⁵ State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.

Abstract

Background: Gastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC.

Methods: Biomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study.

Results: The tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan-Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts.

Conclusion: We found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.

Keywords: biomarker; gastric cancer; hyperthermic intraperitoneal chemotherapy; survival; tumor mutational burden.