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Research Paper|Volume 14, Issue 10|pp 4425—4444

Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer

Wangyang Zheng1,2,7, Xue Bai3, Yongxu Zhou1,2, Liang Yu1,2, Daolin Ji2,5, Yuling Zheng4, Nanfeng Meng1, Hang Wang1, Ziyue Huang1, Wangming Chen1, Judy Wai Ping Yam6, Yi Xu1,2,6, Yunfu Cui1
  • 1Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • 2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150086, China
  • 3Department of Clinic of Internal Medicine I, Ulm University, Ulm 89081, Germany
  • 4Department of Pediatric, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • 5Department of Hepatopancreatobiliary Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • 6Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
  • 7Department II of Gastroenterology, Third Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Received: October 11, 2021Accepted: May 2, 2022Published: May 17, 2022
https://doi.org/10.18632/aging.204080

Copyright: © 2022 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines’ endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.