Research Paper Volume 14, Issue 10 pp 4425—4444
Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer
- 1 Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- 2 The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150086, China
- 3 Department of Clinic of Internal Medicine I, Ulm University, Ulm 89081, Germany
- 4 Department of Pediatric, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- 5 Department of Hepatopancreatobiliary Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150086, China
- 6 Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China
- 7 Department II of Gastroenterology, Third Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Received: October 11, 2021 Accepted: May 2, 2022 Published: May 17, 2022
https://doi.org/10.18632/aging.204080How to Cite
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.