Potential prognostic value of ITPR1 in thyroid carcinoma: An integrated analysis

Purpose: Inositol 1,4,5-trisphosphate receptor type1 (ITPR1) is reported to play an important role in malignancy. We aim to explore the potential role of ITPR1 in thyroid carcinoma (THCA). Method: We collected THCA tissues and adjacent non-cancerous tissues as well as clinical information from 99 patients with THCA (69 females and 30 males). Quantitative real-time quantitative polymerase chain reactions and immunohistochemical were performed to investigate ITPR1 messenger RNA (mRNA) and protein expression between THCA tissues and adjacent non-cancerous tissues, and the relationship between ITPR1 mRNA expression and clinical parameters were analyzed. Bioinformatics techniques were used to analyze ITPR1 in THCA from publicly available datasets including The Cancer Genome Atlas, Gene Expression Omnibus dataset, LinkedOmics, Kaplan Meier plotter, TNMplot, muTarget, TIMER, TIMER2, TISIDB, Gene Expression Profiling Interactive Analysis and Search Tool for the Retrieval of Interacting Genes. Results: ITPR1 mRNA and protein expression was down-regulated in THCA tissues. Low ITPR1 mRNA expression was associated with larger tumor size, lymph node metastasis, advanced stages, and BRAF mutation of TCHA patients. Moreover, the high mRNA expression of ITPR1 is unfavorable in patients with THCA. ITPR1 mRNA expression was positively associated with thyroid iodide-handling genes including TPO, PAX8, TG, TSHR and SLC5A5. And ITPR1 was an autophagy-gene in THCA and participated in autophagy-associated pathways. Additionally, ITPR1 may regulate proliferation capacity in THCA by interacting with microRNAs-144/221/222/ 101/500/501 and involve in drug resistance of cancer treatment via OCT1 family. ITPR1 was potentially correlated with infiltrating levels of tumor-immune cells and CXCL1/2/3/5/8/9/10/11/13/14/16/17. Conclusion: Through clinical data investigation and bioinformatic analysis, this work showed the potential role of ITPR1in carcinogenesis and diagnostic in THCA patients.