PMID- 36801507 OWN - NLM STAT- MEDLINE DCOM- 20230315 LR - 20240102 IS - 1618-0631 (Electronic) IS - 0344-0338 (Linking) VI - 243 DP - 2023 Mar TI - Comprehensive pan-cancer analysis of role of GPRASP1, associated with clinical outcomes, immune microenvironment, and immunotherapeutic efficiency in pancreatic cancer. PG - 154374 LID - S0344-0338(23)00074-2 [pii] LID - 10.1016/j.prp.2023.154374 [doi] AB - BACKGROUND: GPRASP1 (G-protein-coupled receptor-associated sorting protein 1) plays an important role in tumorigenesis. However, GPRASP1 specific role has not been clearly clarified in cancer, particularly in pancreatic cancer(PC). METHODS: Firstly, we utilized pan-cancer analysis based on RNA sequencing data from TCGA (The Cancer Genome Atlas) to evaluate the expression pattern and immunological role of GPRASP1. Then, through multiple transcriptome datasets (TCGA and Gene Expression Omnibus (GEO)) and multi-omics (RNA-seq, DNA methylation, copy number variations (CNV), somatic mutation data) in-depth analysis, we comprehensively explore the relationship of GPRASP1 expression with clinicopathologic characteristics, clinical outcomes, CNV, and DNA methylation in pancreatic cancer. Additionally, we employed immunohistochemistry (IHC) to further confirm GPRASP1 expression pattern between PC tissues and paracancerous tissues. Lastly, we systematically associated the GPRASP1 with immunological properties from numerous perspectives, such as immune cell infiltration, immune-related pathways, immune checkpoint inhibitors, immunomodulators, immunogenicity, and immunotherapy. RESULTS: Through pan-cancer analysis, we identified that GPRASP1 plays a critical role in the occurrence and prognosis of PC, and is closely related to immunological characteristics in PC. IHC analysis confirmed that GPRASP1 is significantly down-regulated in PC compared with normal tissues. The expression of GPRASP1 is significantly negatively correlated with clinical features (histologic grade, T stage, and TNM stage), and is an independent predictor of favorable prognosis, regardless of other clinicopathological features (HR: 0.69, 95% CI 0.54-0.92, p= 0.011). The etiological investigation found that the abnormal expression of GPRASP1 was related to DNA methylation and CNV frequency. Subsequently, the high expression of GPRASP1 was significantly correlated with immune cell infiltration (CD8 + T cell, tumor-infiltrating lymphocyte(TIL)), immune-related pathways(cytolytic activity, check-point, human leukocyte antigen (HLA)), immune checkpoint inhibitors (CTLA4, HAVCR2, LAG3, PDCD1 and TIGIT), immunomodulators ( CCR4/5/6, CXCL9, CXCR4/5), and immunogenicity(immune score, neoantigen, TMB(tumor mutation burden)). Finally, IPS (immunophenoscore) and TIDE (tumor immune dysfunction and exclusion) analysis demonstrated that GPRASP1 expression levels can accurately predict the immunotherapeutic response. CONCLUSION: GPRASP1 is a promising candidate biomarker that plays a role in the occurrence, development, and prognosis of PC. Evaluating GPRASP1 expression will aid in the characterization of tumor microenvironment (TME) infiltration and orient more efficient immunotherapy strategies. CI - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Du, Jiaxing AU - Du J AD - Department of Surgical Oncology, Xinyang Central Hospital, Xinyang 464000, Henan Province, PR China. Electronic address: djx13131313@126.com. FAU - Chen, Yongsheng AU - Chen Y AD - Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong Province, PR China. Electronic address: 318483790@qq.com. FAU - Liu, Genglong AU - Liu G AD - Department of Pathology, Shunde Hospital, Southern Medical University (The First people's hospital of Shunde), Foshan 528308, Guangdong Province, PR China; Baishideng Publishing Group Inc, Pleasanton, CA 94566, United States. Electronic address: lglong3@mail2.sysu.edu.cn. FAU - Zeng, Qingxing AU - Zeng Q AD - Department of Intensive Care Unit, Xinyang Central Hospital, Xinyang 464000, Henan Province, PR China. Electronic address: gszengxing@163.com. FAU - Zhou, Nan AU - Zhou N AD - Department of Surgical Oncology, Xinyang Central Hospital, Xinyang 464000, Henan Province, PR China. Electronic address: ntzhounan@126.com. FAU - Du, Dajun AU - Du D AD - Department of Surgical Oncology, Xinyang Central Hospital, Xinyang 464000, Henan Province, PR China. Electronic address: ddjys2009@163.com. LA - eng PT - Journal Article DEP - 20230212 PL - Germany TA - Pathol Res Pract JT - Pathology, research and practice JID - 7806109 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (GPRASP1 protein, human) RN - 0 (Vesicular Transport Proteins) SB - IM MH - Humans MH - Carcinogenesis MH - *DNA Copy Number Variations MH - Immune Checkpoint Inhibitors MH - *Pancreatic Neoplasms/genetics/therapy MH - Prognosis MH - Tumor Microenvironment MH - *Vesicular Transport Proteins/genetics OTO - NOTNLM OT - GPRASP1 OT - Immunotherapy OT - Pan-cancer analysis OT - Pancreatic cancer OT - Tumor microenvironment COIS- Conflict of Interest All the authors report no relevant conflicts of interest for this article. EDAT- 2023/02/22 06:00 MHDA- 2023/03/14 06:00 CRDT- 2023/02/21 16:23 PHST- 2022/09/27 00:00 [received] PHST- 2023/01/05 00:00 [revised] PHST- 2023/02/10 00:00 [accepted] PHST- 2023/02/22 06:00 [pubmed] PHST- 2023/03/14 06:00 [medline] PHST- 2023/02/21 16:23 [entrez] AID - S0344-0338(23)00074-2 [pii] AID - 10.1016/j.prp.2023.154374 [doi] PST - ppublish SO - Pathol Res Pract. 2023 Mar;243:154374. doi: 10.1016/j.prp.2023.154374. Epub 2023 Feb 12.