Differential Expression and Clinical Significance of MIA3 Based on Bioinformatics Analysis in Pan-Cancer

doi:10.13438/j.cnki.jdzk.2025.02.010

Abstract

Abstract: To elucidate the expression profile and role of MIA3 in pan-cancer,we collected data from TCGA and other databases and employed bioinformatics methods to explore the associations between MIA3 and clinical prognosis as well as immune-related characteristics in various cancers.Results showed that MIA3 expression was significantly upregulated in invasive breast cancer,bladder urothelial carcinoma,esophageal cancer,head and neck squamous cell carcinoma,renal clear cell carcinoma,mixed renal cancer,hepatocellular carcinoma,lung adenocarcinoma,lung squamous cell carcinoma,prostate cancer,gastric cancer,and gastroesophageal cancer,while it was significantly downregulated in renal chromophobe carcinoma and thyroid carcinoma.The highest mutation frequency of MIA3 was observed in endometrial cancer (11.4%),followed by gastric cancer (6.1%).In most cancers,especially ovarian serous cystadenoma,brain low-grade glioma,glioblastoma multiforme,renal papillary cell carcinoma,and mixed renal cancer,MIA3 expression was positively correlated with DNA methyltransferase expression.High expression of MIA3 was a risk factor for poor prognosis in adrenocortical carcinoma,renal chromophobe carcinoma,renal papillary cell carcinoma,mixed renal cancer,and brain low-grade glioma.Conversely,low expression of MIA3 was associated with poor prognosis in cutaneous melanoma and ovarian serous cystadenoma.The infiltration of cancer immune cells,including B cells,CD4+T lymphocytes,CD8+T lymphocytes,neutrophils,dendritic cells,and macrophages,was significantly correlated with MIA3 expression.Additionally,MIA3 expression was positively correlated with stromal and immune scores in colorectal cancer,mixed renal cancer,head and neck squamous cell carcinoma,renal clear cell carcinoma,testicular germ cell tumors,and renal chromophobe carcinoma.These findings suggest that MIA3 may serve as a valuable prognostic biomarker and potential therapeutic target for multiple cancers.However,further studies are needed to confirm these findings

Key words: MIA3, pan-cancer, bioinformatics, immune cell, infiltration

CHEN Gonghua1, OU Pengfei, ZHEN Yao1, 3, XIA Jie1, MAN Jing. Differential Expression and Clinical Significance of MIA3 Based on Bioinformatics Analysis in Pan-Cancer[J]. Journal of Jishou University(Natural Sciences Edition), 2025, 46(2): 78-89.

References

[1] BRAY FREDDIE,LAVERSANNE MATHIEU,SUNG HYUNA,et al.Global Cancer Statistics 2022:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J].CA:A Cancer Journal for Clinicians,2024,74(3):229-263.
[2] KRAEHENBUEHL LUKAS,WENG CHIEN-HUAN,EGHBALI SHABNAM,et al.Enhancing Immunotherapy in Cancer by Targeting Emerging Immunomodulatory Pathways[J].Nature Reviews Clinical Oncology,2022,19(1):37-50.
[3] STOLL RAPHAEL,BOSSERHOFF ANJA K.Extracellular SH3 Domain Containing Proteins-Features of a New Protein Family[J].Current Protein and Peptide Science,2008,9(3):221-226.
[4] MCCAUGHEY JANINE,STEVENSON NICOLA L,MANTELL JUDITH M,et al.A General Role for TANGO1,Encoded by MIA3,in Secretory Pathway Organization and Function[J].Journal of Cell Science,2021,134(17):jcs259075.DOI:10.1242/jcs.259075.
[5] RAOTE ISHIER,MALHOTRA VIVEK.Tunnels for Protein Export from the Endoplasmic Reticulum[J].Annual Review of Biochemistry,2021,90:605-630.
[6] ARNOLDS OLIVER,STOLL RAPHAEL.Characterization of a Fold in TANGO1 Evolved from SH3 Domains for the Export of Bulky Cargos[J].Nature Communications,2023,14(1):2273.DOI:10.1038/s41467-023-37705-4.
[7] LEI Yu,XU Jianfei,LI Mengju,et al.MIA SH3 Domain ER Export Factor 3 Deficiency Prevents Neointimal Formation by Restoring BAT-Like PVAT and Decreasing VSMC Proliferation and Migration[J].Frontiers in Endocrinology,2021,12:748216.DOI:10.3389/fendo.2021.748216.
[8] ARNDT STEPHANIE,MELLE CHRISTIAN,MONDAL KRISHNA,et al.Interactions of TANGO and Leukocyte Integrin CD11c/CD18 Regulate the Migration of Human Monocytes[J].Journal of Leukocyte Biology,2007,82(6):1466-1472.
[9] LU Zhihao,CHEN Yang,LIU Dan,et al.The Landscape of Cancer Research and Cancer Care in China[J].Nature Medicine,2023,29(12):3022-3032.
[10] LIU Chang,YU Hui,SHEN Xuxia,et al.Prognostic Significance and Biological Function of Lamina-Associated Polypeptide 2 in Non-Small-Cell Lung Cancer[J].OncoTargets and Therapy,2019,12:3817-3827.
[11] ARIDOR MEIR.COPⅡ Gets in Shape:Lessons Derived from Morphological Aspects of Early Secretion[J].Traffic,2018,19(11):823-839.
[12] SAITO KOTA,KATADA TOSHIYAKI.Mechanisms for Exporting Large-Sized Cargoes from the Endoplasmic Reticulum[J].Cell and Molecular Life Sciences,2015,72(19):3709-3720.
[13] MALHOTRA VIVEK,ERLMAN PATRIK,NOGUEIRA CRISTINA.Procollagen Export from the Endoplasmic Reticulum[J].Biochemical Society Transactions,2015,43(1):104-107.
[14] ARNDT STEPHANIE,BOSSERHOFF ANJA K.TANGO is a Tumor Suppressor of Malignant Melanoma[J].International Journal of Cancer,2006,119(12):2812-2820.
[15] DU Qiong,YE Xuan,LU Shengrong,et al.Exosomal MiR-30a and MiR-222 Derived from Colon Cancer Mesenchymal Stem Cells Promote the Tumorigenicity of Colon Cancer Through Targeting MIA3[J].Journal of Gastrointestinal Oncology,2021,12(1):52-68.
[16] SASAHIRA TOMONORI,KIRITA TADAAKI,YAMAMOTO KAZUHIKO,et al.Transport and Golgi Organisation Protein 1 is a Novel Tumour Progressive Factor in Oral Squamous Cell Carcinoma[J].European Journal of Cancer,2014,50(12):2142-2151.
[17] SASAHIRA TOMONORI,KIRITA TADAAKI,NISHIGUCHI YUKIKO,et al.A Comprehensive Expression Analysis of the MIA Gene Family in Malignancies:MIA Gene Family Members are Novel,Useful Markers of Esophageal,Lung,and Cervical Squamous Cell Carcinoma[J].Oncotarget,2016,7(21):31137-31152.
[18] ZHANG Qiang,YIN Xiujuan,PAN Zhiwei,et al.Identification of Potential Diagnostic and Prognostic Biomarkers for Prostate Cancer[J].Oncology Letters,2019,18(4):4237-4245.
[19] MAN Jing,ZHOU Wanbiao,ZUO Shi,et al.TANGO1 Interacts with NRTN to Promote Hepatocellular Carcinoma Progression by Regulating the PI3K/AKT/mTOR Signaling Pathway[J].Biochemical Pharmacology,2023,213:115615.DOI:10.1016/j.bcp.2023.115615.
[20] ZHOU Wanbiao,MAN Jing,ZUO Shi,et al.MIA3 Promotes the Degradation of GSH (Glutathione) by Binding to CHAC1,Thereby Promoting the Progression of Hepatocellular Carcinoma[J].Molecular and Cellular Biochemistry,2024,479:2769-2784.
[21] ZHANG Shaosen,XIAO Xinyi,YI Yonglin,et al.Tumor Initiation and Early Tumorigenesis:Molecular Mechanisms and Interventional Targets[J].Signal Transduction and Targeted Therapy,2024,9(1):149.DOI:10.1038/s41392-024-01848-7.
[22] LI Jun,HUBISZ MELISSA J,EARLIE ETHAN M,et al.Non-Cell-Autonomous Cancer Progression from Chromosomal Instability[J].Nature,2023,620(7976):1080-1088.
[23] BAHAROM FAEZZAH,RAMIREZ-VALDEZ RAMIRO A,KHALILNEZHAD AHAD,et al.Systemic Vaccination Induces CD8(+) T Cells and Remodels the Tumor Microenvironment[J].Cell,2022,185(23):4317-4332.
[24] SADEGHI RAD HABIB,MONKMAN JAMES,WARKIANI MAJID E,et al.Understanding the Tumor Microenvironment for Effective Immunotherapy[J].Medical Research Reviews,2021,41(3):1474-1498.
[25] BRUNI DANIELA,ANGELL HELEN K,GALON JRME.The Immune Contexture and Immunoscore in Cancer Prognosis and Therapeutic Efficacy[J].Nature Reviews Cancer,2020,20(11):662-680.
[26] LEE SEUNG-TAE,WIELMELS JOSEPH L.Genome-Wide CpG Island Methylation and Intergenic Demethylation Propensities Vary Among Different Tumor Sites[J].Nucleic Acids Research,2016,44(3):1105-1117.
[27] MAJUMDER SHOUNAK,TAYLOR WILLIAM R,YAB TRACY C,et al.Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts:Marker Discovery,Tissue Validation,and Cyst Fluid Testing[J].American Journal of Gastroenterology,2019,114(9):1539-1549.