|Table of Contents|

Expression of GPX8 in breast cancer and its clinical significance

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 05
Page:
848-856
Research Field:
Publishing date:

Info

Title:
Expression of GPX8 in breast cancer and its clinical significance
Author(s):
LI He1ZHAO Yanchun2HAN Jianjun3ZHUO Jian1DAI Luxian4SHENG Ankang4YAO Hanyu4LIU Weiguang4
1.School of Clinical Medicine,Hebei University of Engineering,Hebei Handan 056002,China;2.Department of Outpatient;3.Department of Breast Surgery,Affiliated Hospital of Hebei University of Engineering,Hebei Handan 056002,China;4.Department of Mammary Gland,Yangzhou Maternal and Child Health Hospital,Yangzhou University,Jiangsu Yangzhou 225002,China.
Keywords:
breast cancerGPX8prognosisTILsTNBC
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.05.012
Abstract:
Objective:We utilized bioinformatics analysis,immunohistochemistry,and clinical cohort analysis to predict,analyze,and assess the differential expression,diagnostic potential,and prognostic significance of GPX8 in the context of breast cancer.Methods:We downloaded GPX8 gene expression,RNAseq,DNA methylation,survival,phenotype,dry score,and clinical information data of patients with cancer from the UCSC Xena database and conducted a Kaplan-Meier survival prognosis analysis,and explored methylation levels.The correlation between GPX8 and tumor-infiltrating lymphocytes in breast cancer was evaluated using the tumor immune estimation resource(TIMER),and the potential functional pathways affected by GPX8 were analyzed using gene set enrichment analysis(GSEA).A total of 125 patients who were diagnosed with breast cancer underwent immunohistochemical and HE staining,followed by clinical follow-up analysis of GPX8.GPX8 expression levels and prognostic relationships in different subgroups were analyzed using the Chi-square test and Cox regression.Results:Gene expression profiling interaction analysis(GEPIA) and TIMER analysis revealed that GPX8 mRNA expression in patients with breast cancer was higher in para-cancer tissues,and the prognosis was significantly different.GPX8 protein expression was highest in triple-negative breast cancer.In the TIMER database,the mRNA expression of GPX8 was found to be negatively correlated with the infiltration of CD8+T,B cells,NK,and Treg cells.Furthermore,within the clinical cohort,an observation has been made indicating a positive correlation between GPX8 mRNA expression and factors such as TNM stage,T stage,and molecular subtypes.Additionally,in patients with triple-negative breast cancer,the expression levels of GPX8 were found to be negatively correlated with tumor-infiltrating lymphocytes(TILs).Patients with high GPX8 expression had significantly reduced overall survival and an increased risk of death.Conclusion:GPX8 is expressed differently in breast cancer tissues and can be used as an effective prognostic biomarker for clinical diagnosis.

References:

[1]ARNOLD M,MORGAN E,RUMGAY H,et al.Current and future burden of breast cancer:Global statistics for 2020 and 2040[J].Breast,2022,66:15-23.
[2]DESANTIS C,HOWLADER N,CRONIN KA,et al.Breast cancer incidence rates in U.S. women are no longer declining[J].Cancer Epidemiol Biomarkers Prev,2011,20(5):733-739.
[3]SUI S,AN X,XU C,et al.An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer[J].Theranostics,2020,10(26):11938-11949.
[4]MARIOTTI M,RIDGE PG,ZHANG Y,et al.Composition and evolution of the vertebrate and mammalian selenoproteomes[J].PLoS One,2012,7(3):e33066.
[5]LIU J,HINKHOUSE MM,SUN W,et al.Redox regulation of pancreatic cancer cell growth:Role of glutathione peroxidase in the suppression of the malignant phenotype[J].Hum Gene Ther,2004,15(3):239-250.
[6]HANGAUER MJ,VISWANATHAN VS,RYAN MJ,et al.Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition[J].Nature,2017,551(7679):247-250.
[7]NGUYEN VD,SAARANEN MJ,KARALA AR,et al.Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation[J].J Mol Biol,2011,406(3):503-515.
[8]ENYEDI B,VARNAI P,GEISZT M.Redox state of the endoplasmic reticulum is controlled by Ero 1L-alpha and intraluminal calcium[J].Antioxidants & Redox Signaling,2010,13(6):721-729.
[9]SENER DE,GONENC A,AKINCI M,et al.Lipid peroxidation and total antioxidant status in patients with breast cancer[J].Cell Biochem Funct,2007,25(4):377-382.
[10]TOPPO S,VANIN S,BOSELLO V,et al.Evolutionary and structural insights into the multifaceted glutathione peroxidase (Gpx) superfamily[J].Antioxid Redox Signal,2008,10(9):1501-1514.
[11]KHATIB A,SOLAIMUTHU B,BEN YM,et al.The glutathione peroxidase 8(GPX8)/IL-6/STAT3 axis is essential in maintaining an aggressive breast cancer phenotype[J].Proc Natl Acad Sci USA,2020,117(35):21420-21431.
[12]GOLDMAN MJ,CRAFT B,HASTIE M,et al.Visualizing and interpreting cancer genomics data via the Xena platform[J].Nat Biotechnol,2020,38(6):675-678.
[13]BARRETT T,WILHITE SE,LEDOUX P,et al.NCBI GEO:Archive for functional genomics data sets-update[J].Nucleic Acids Res,2013,41(Database issue):D991-D995.
[14]RITCHIE ME,PHIPSON B,WU D,et al.Limma powers differential expression analyses for RNA-sequencing and microarray studies[J].Nucleic Acids Res,2015,43(7):e47.
[15]LI B,SEVERSON E,PIGNON JC,et al.Comprehensive analyses of tumor immunity:Implications for cancer immunotherapy[J].Genome Biol,2016,17(1):174.
[16]SUBRAMANIAN A,KUEHN H,GOULD J,et al.GSEA-P:A desktop application for gene set enrichment analysis[J].Bioinformatics,2007,23(23):3251-3253.
[17]SUBRAMANIAN A,TAMAYO P,MOOTHA VK,et al.Gene set enrichment analysis:A knowledge-based approach for interpreting genome-wide expression profiles[J].Proc Natl Acad Sci USA,2005,102(43):15545-15550.
[18]CHEN Z,ZHAO Y,TIAN Y,et al.Pan-cancer analysis of the TRP family,especially TRPV4 and TRPC4,and its expression correlated with prognosis,tumor microenvironment,and treatment sensitivity[J].Biomolecules,2023,13(2):282.
[19]DENKERT C,VON MINCKWITZ G,DARB-ESFAHANI S,et al.Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer:A pooled analysis of 3771 patients treated with neoadjuvant therapy[J].Lancet Oncol,2018,19(1):40-50.
[20]HINSHAW DC,SHEVDE LA.The tumor microenvironment innately modulates cancer progression[J].Cancer Res,2019,79(18):4557-4566.
[21]VIALE PH.The American Cancer Society's Facts & Figures:2020 edition[J].J Adv Pract Oncol,2020,11(2):135-136.
[22]ZEESHAN HM,LEE GH,KIM HR,et al.Endoplasmic reticulum stress and associated ROS[J].Int J Mol Sci,2016,17(3):327.
[23]SABHARWAL SS,SCHUMACKER PT.Mitochondrial ROS in cancer:Initiators,amplifiers or an Achilles' heel[J].Nat Rev Cancer,2014,14(11):709-721.
[24]SO JY,SKRYPEK N,YANG HH,et al.Induction of DNMT3B by PGE2 and IL6 at distant metastatic sites promotes epigenetic modification and breast cancer colonization[J].Cancer Res,2020,80(12):2612-2627.
[25]MALTA TM,SOKOLOV A,GENTLES AJ,et al.Machine learning identifies stemness features associated with oncogenic dedifferentiation[J].Cell,2018,173(2):338-354.
[26]REN Z,HE Y,YANG Q,et al.A Comprehensive analysis of the glutathione peroxidase 8(GPX8) in human cancer[J].Front Oncol,2022,12:812811.
[27]GRASSET EM,DUNWORTH M,SHARMA G,et al.Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin[J].Sci Transl Med,2022,14(656):n7571.
[28]NALLASAMY P,NIMMAKAYALA RK,KARMAKAR S,et al.Pancreatic tumor microenvironment factor promotes cancer stemness via SPP1-CD44 axis[J].Gastroenterology,2021,161(6):1998-2013.
[29]PANTELIDOU C,SONZOGNI O,DE OLIVERIA TM,et al.PARP inhibitor efficacy depends on CD8(+) T-cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer[J].Cancer Discov,2019,9(6):722-737.
[30]GU Y,LIU Y,FU L,et al.Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG[J].Nat Med,2019,25(2):312-322.
[31]VERMA C,KAEWKANGSADAN V,EREMIN JM,et al.Natural killer(NK) cell profiles in blood and tumour in women with large and locally advanced breast cancer(LLABC) and their contribution to a pathological complete response(PCR) in the tumour following neoadjuvant chemotherapy(NAC):Differential restoration of blood profiles by NAC and surgery[J].J Transl Med,2015,13:180.
[32]WCULEK SK,MALANCHI I.Neutrophils support lung colonization of metastasis-initiating breast cancer cells[J].Nature,2015,528(7582):413-417.
[33]LIU Z,GAO Z,LI B,et al.Lipid-associated macrophages in the tumor-adipose microenvironment facilitate breast cancer progression[J].Oncoimmunology,2022,11(1):2085432.
[34]CIMPEAN AM,TAMMA R,RUGGIERI S,et al.Mast cells in breast cancer angiogenesis[J].Crit Rev Oncol Hematol,2017,115:23-26.
[35]KEENAN TE,TOLANEY SM.Role of immunotherapy in triple-negative breast cancer[J].J Natl Compr Canc Netw,2020,18(4):479-489.
[36]孙健健,魏敏杰.三阴性乳腺癌免疫治疗研究新进展[J].现代肿瘤医学,2017,25(7):1144-1147. SUN JJ,WEI MJ.Research progress on the immunotherapy of the triple-negative breast cancer[J].Modern Oncology,2017,25(7):1144-1147.
[37]董静,牛昆,庞丽然,等.免疫治疗相关单克隆抗体靶点在三阴性乳腺癌中的研究现状[J].现代肿瘤医学,2021,29(22):4044-4049. DONG J,NIU K,PANG LR,et al.Current status of immunotherapy-related monoclonal antibody targets in triple-negative breast cancer[J].Modern Oncology,2021,29(22):4044-4049.

Memo

Memo:
河北省自然科学基金(编号:H2021402015)
Last Update: 2024-01-30