Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy

Quynh-Anh Nguyen; Wan-Hsuan Chou; Mao-Chih Hsieh; Che-Mai Chang; Wei-Tzu Luo; Yu-Ting Tai; Wei-Chiao Chang

doi:10.3389/fonc.2023.1054406

Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy

Front Oncol. 2023 Apr 26:13:1054406. doi: 10.3389/fonc.2023.1054406. eCollection 2023.

Authors

Quynh-Anh Nguyen¹, Wan-Hsuan Chou¹, Mao-Chih Hsieh², Che-Mai Chang¹, Wei-Tzu Luo¹, Yu-Ting Tai^{3

4}, Wei-Chiao Chang^{1

5

6

7}

Affiliations

¹ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
² Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
³ Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁵ Master Program in Clinical Genomics and Proteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁷ Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

Abstract

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered for patients with peritoneal metastasis (PM). However, patients selection that relies on conventional prognostic factors is not yet optimal. In this study, we performed whole exome sequencing (WES) to establish tumor molecular characteristics and expect to identify prognosis profiles for PM management.

Methods: In this study, blood and tumor samples were collected from patients with PM before HIPEC. Tumor molecular signatures were determined using WES. Patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Genomic characteristics between the two cohorts were compared to study potential targets.

Results: In total, 15 patients with PM were enrolled in this study. Driver genes and enriched pathways were identified from WES results. AGAP5 mutation was found in all responders. This mutation was significantly associated with better OS (p = 0.00652).

Conclusions: We identified prognostic markers that might be useful to facilitate decision-making before CRS/HIPEC.

Keywords: AGAP5; hyperthermic intraperitoneal chemotherapy (HIPEC); peritoneal metastasis; somatic mutation; whole exome sequencing (WES).

Grants and funding

This work was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 110-2628-B-038-020; MOST 110-2314-B-038-161, and MOST 110-2321-B-038-002 - Establishing A Translational Female Cancer Biomedical Big Data Bank and Developing Precision Medicine Healthcare System).