«Previous Article|Table of Contents|Next Article»

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

Issue:

2024 19

Page:

3636-3642

Research Field:

Publishing date:

Info

Title:

Potential ferroptosis biomarkers and immune cell infiltration characteristics in oral squamous cell carcinoma using WGCNA analysis

Author(s):

SHU Jiayu¹; WANG Huan¹; LU Jing¹; CHEN Helin²; DONG Qiang²

1.School of Stomatology,Guizhou Medical University，Guizhou Guiyang 550004,China;2.Department of Prosthodontics and Implantology,Affiliated Stomatological Hospital of Guizhou Medical University,Guizhou Guiyang 550004,China.

Keywords:

oral squamous cell carcinoma; ferroptosis; differentially expressed genes; weighted gene co-expression network analysis; immune cell infiltration

PACS:

R739.8

DOI:

10.3969/j.issn.1672-4992.2024.19.002

Abstract:

Objective:To screen novel biomarkers related to ferroptosis in oral squamous cell carcinoma(OSCC) and analyze immune cell infiltration.Methods:The OSCC datasets were downloaded from the GEO database.Differentially expressed genes(DEGs) were screened by R and functional and pathway enrichment analysis was performed.The interaction modules between genes were explored by weighted gene co-expression network analysis(WGCNA),crossed with DEGs to obtain key genes and verified in clinical samples.ROC analysis and survival analysis were performed on key genes and immune cell infiltration was analyzed using CIBERSORT.Results:A total of 19 DEGs and 3 key genes(CHAC1,PGD,PTGS2) were screened out,among which CHAC1 and PGD were significantly downregulated in OSCC,while PTGS2 was significantly upregulated.DEGs were mainly involved in glutathione biosynthetic process,nonribosomal peptide biosynthetic process,response to oxidative stress process,glutathione metabolic process and cellular modified amino acid biosynthesis process.KEGG analysis showed an obvious enrichment of signaling pathways such as glutathione metabolism，ferroptosis and pentose phosphate pathway.The ROC analysis showed a high diagnostic value of PGD,CHAC1,and PTGS2.Survival analysis showed that the expression levels of CHAC1,PGD,and PTGS2 in OSCC were significantly correlated with prognosis.Immune cell infiltration analysis showed statistically significant differences in CD4+T cell,T cells regulatory(Tregs),CD8+ T cells,neutrophils and dendritic cells activated(all P＜0.05).Conclusion:CHAC1,PGD,and PTGS2 may serve as potential diagnostic and prognostic biomarkers.The activation of CD4+T cell,T cells regulatory(Tregs),CD8+ T cells,neutrophils and dendritic cells activated participates in the occurrence and development of OSCC,providing some reference basis for the early diagnosis,prognosis and molecular mechanism study of OSCC.

References:

[1]TAN Y,WANG Z,XU M,et al.Oral squamous cell carcinomas:state of the field and emerging directions［J］.Int J Oral Sci,2023,15(1):44.
[2] BADWELAN M,MUADDI H,AHMED A,et al.Oral squamous cell carcinoma and concomitant primary tumors,what do we know?A review of the literature［J］.Curr Oncol,2023,30(4):3721-3734.
[3] NOKOVITCH L,MAQUET C,CRAMPON F,et al.Oral cavity squamous cell carcinoma risk factors:State of the art［J］.J Clin Med,2023,12(9):3264.
[4] THOMSON PJ.Perspectives on oral squamous cell carcinoma prevention-proliferation,position,progression and prediction［J］.J Oral Pathol Med,2018,47(9):803-807.
[5] RICH BJ,SAMUELS SE,AZZAM GA,et al.Oral cavity squamous cell carcinoma:Review of pathology,diagnosis,and management［J］.Crit Rev Oncog,2024,29(3):5-24.
[6] PEKAREK L,GARRIDO-GIL MJ,SANCHEZ-CENDRA A,et al.Emerging histological and serological biomarkers in oral squamous cell carcinoma:Applications in diagnosis,prognosis evaluation and personalized therapeutics(Review)［J］.Oncol Rep,2023,50(6):213.
[7] DIXON SJ,LEMBERG KM,LAMPRECHT MR,et al.Ferroptosis:an iron-dependent form of nonapoptotic cell death［J］.Cell,2012,149(5):1060-1072.
[8] LI Y,LI X,LI J,et al Ferroptosis in lung cancer:dual role,multi-level regulation,and new therapeutic strategies［J］.Front Oncol,2024,14:1360638.
[9] MO Y,ZOU Z,CHEN E.Targeting ferroptosis in hepatocellular carcinoma［J］.Hepatol Int,2024,18(1):32-49.
[10] EL-BENHAWY SA,ABDELRHMAN IG,SADEK NA,et al.Studying ferroptosis and iron metabolism pre- and post-radiotherapy treatment in breast cancer patients［J］.J Egypt Natl Canc Inst,2023,35(1):4.
[11] ZHOU L,WU Y,YING Y,et al.Current knowledge of ferroptosis in the pathogenesis and prognosis of oral squamous cell carcinoma［J］.Cell Signal,2024,119:111176.
[12] GAO S,MIAO BL,MO QZ,et al.Research progress on ferroptosis in the treatment of urinary tract tumors［J］.Modern Oncology,2023,31（13）：2522-2526.
[13] 邱强民,李彦泽,杜洋,等.铁死亡在肾细胞癌发生发展和治疗中的作用及机制研究进展［J］.现代肿瘤医学,2022,30（20）：3789-3793. QIU QM,LI YZ,DU Y,et al.Research progress on the role and mechanism of ferroptosis in the development and treatment of renal cell carcinoma［J］.Modern Oncology,2022,30（20）：3789-3793.
[14] WU JE,LI Y,HOU J.Downregulation of SLC3A2 mediates immune evasion and accelerates metastasis in oral squamous cell carcinoma［J］.J Cell Mol Med,2023,28(5):e18010.
[15] ZHAO YY,LIAN JX,LAN Z,et al.Ferroptosis promotes anti-tumor immune response by inducing immunogenic exposure in HNSCC［J］.Oral Dis,2023,29(3):933-941.
[16] ALSAEEDI SM,AGGARWAL S.The holistic review on occurrence,biology,diagnosis,and treatment of oral squamous cell carcinoma［J］.Cureus,2022,14(10):e30226.
[17] GU W,KIM M,WANG L,et al.Multi-omics analysis of ferroptosis regulation patterns and characterization of tumor microenvironment in patients with oral squamous cell carcinoma［J］.Int J Biol Sci,2021,17(13):3476-3492.
[18] KENNEDY L,SANDHU JK,HARPER ME,et al.Role of glutathione in cancer:From mechanisms to therapies［J］.Biomolecules,2020,10(10):1429.
[19] SINHA R,SINHA I,CALCAGNOTTO A,et al.Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function［J］.Eur J Clin Nutr,2018,72(1):105-111.
[20] FAN L,WANG J,XIA C,et al.Glutathione-sensitive and folate-targeted nanoparticles loaded with paclitaxel to enhance oral squamous cell carcinoma therapy［J］.J Mater Chem B,2020,8(15):3113-3122.
[21] SUMI D,TAGUCHI H,TAKEUCHI K,et al.CHAC1 exacerbates arsenite cytotoxicity by lowering intracellular glutathione levels［J］.J Toxicol Sci,2023,48(9):487-494.
[22] LIU Y,WU D,FU Q,et al.CHAC1 as a novel contributor of ferroptosis in retinal pigment epithelial cells with oxidative damage［J］.Int J Mol Sci,2023,24(2):1582.
[23] HE S,ZHANG M,YE Y,et al.ChaC glutathione specific γ-glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis［J］.Exp Ther Med,2021,22(3):997.
[24] WANG X,HE MJ,CHEN XJ,et al.Glaucocalyxin a impairs tumor growth via amplification of the ATF4/CHOP/CHAC1 cascade in human oral squamous cell carcinoma［J］.J Ethnopharmacol,2022,290:115100.
[25] REN Z,HU M,WANG Z,et al.Ferroptosis-related genes in lung adenocarcinoma:Prognostic signature and immune,drug resistance,mutation analysis［J］.Front Genet,2021,12:672904.
[26] DUBREUIL MM,MORGENS DW,OKUMOTO K,et al.Systematic identification of regulators of oxidative stress reveals non-canonical roles for peroxisomal import and the pentose phosphate pathway［J］.Cell Rep,2020,30(5):1417-1433.e7.
[27] BECHARD ME,WORD AE,TRAN AV,et al.Pentose conversions support the tumorigenesis of pancreatic cancer distant metastases［J］.Oncogene,2018,37(38):5248-5256.
[28] SAMPILVANJIL A,KARASAWA T,YAMADA N,et al.Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells［J］.Am J Physiol Heart Circ Physiol,2020,318(3):508-518.
[29] KAMAL MV,DAMERLA RR,DIKHIT PS,et al.Prostaglandin-endoperoxide synthase 2(PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma［J］.J Oral Biol Craniofac Res,2023,13(5):567-574.
[30] FENG B,SHEN Y,PASTOR HOSTENCH X,et al.Integrative analysis of multi-omics data identified EGFR and PTGS2 as key nodes in a gene regulatory network related to immune phenotypes in head and neck cancer［J］.Clin Cancer Res,2020,26(14):3616-3628.
[31] LI D,LIU S,XU J,et al.Ferroptosis-related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma［J］.J Cell Mol Med,2021,25(7):3610-3621.
[32] XIAO R,WANG S,GUO J,et al.Ferroptosis-related gene NOX4,CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma［J］.J Cell Mol Med,2022,26(4):1183-1193.
[33] WANG L,YE S,QIN J,et al.Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis［J］.J Orthop Surg Res,2023,18(1):699.
[34] HE X,ZHANG J,GONG M,et al.Identification of potential ferroptosis-associated biomarkers in rheumatoid arthritis［J］.Front Immunol,2023,14:1197275.
[35] NOBLE A,PRING ET,DURANT L,et al.Altered immunity to microbiota,B cell activation and depleted γδ/resident memory T cells in colorectal cancer［J］.Cancer Immunol Immunother,2022,71(11):2619-2629.
[36] WEI W,LI J,SHEN X,et al.Oral microbiota from periodontitis promote oral squamous cell carcinoma development via γδ T cell activation［J］.mSystems,2022,7(5):e0046922.

Memo

Memo:

National Natural Science Foundation of China（No.82160186）;国家自然科学基金地区项目(编号：82160186)

Common functions

Last Update: 2024-08-30