Synapse - Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues

Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues Journal Article

Authors:	Moukarzel, L. A.; Ferrando, L.; Dopeso, H.; Stylianou, A.; Basili, T.; Pareja, F.; Da Cruz Paula, A.; Zoppoli, G.; Abu-Rustum, N. R.; Reis-Filho, J. S.; Long Roche, K.; Tew, W. P.; Chi, D. S.; Sonoda, Y.; Zamarin, D.; Aghajanian, C.; O'Cearbhaill, R. E.; Zivanovic, O.; Weigelt, B.
Article Title:	Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues
Abstract:	Objective: To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues. Methods: Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting. Results: RNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues. Conclusions: HIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors. © 2022 Elsevier Inc.
Keywords:	genetics; multimodality cancer therapy; combined modality therapy; ovarian cancer; cytoreductive surgery; ovarian neoplasms; metabolism; carboplatin; gene expression; rna; immune response; ovary tumor; hyperthermia, induced; transcriptome; heat shock; thermotherapy; heat-shock proteins; heat shock protein; procedures; hyperthermic intraperitoneal chemotherapy; humans; human; female; hipec; cytoreduction surgical procedures
Journal Title:	Gynecologic Oncology
Volume:	165
Issue:	2
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2022-05-01
Start Page:	239
End Page:	247
Language:	English
DOI:	10.1016/j.ygyno.2022.02.022
PUBMED:	35292180
PROVIDER:	scopus
PMCID:	PMC9064951
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126320889&doi=10.1016%2fj.ygyno.2022.02.022&partnerID=40&md5=f39edacad4e6839c6aede5ee892ef32c
Notes:	Article -- Export Date: 1 June 2022 -- Source: Scopus