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. 2024 Jan;52(1):3000605231221361.
doi: 10.1177/03000605231221361.

Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer

Zhitao Chen  1 , Chenchen Ding  1 , Jun Chen  1   2   3 , Shusen Zheng  1 , Qiyong Li  1
Affiliations

"VSports注册入口" Pan-cancer analysis revealing the multidimensional expression and prognostic and immunologic roles of TGFB1 in cancer

VSports app下载 - Zhitao Chen et al. J Int Med Res. 2024 Jan.

Abstract

Objective: This study aimed to perform an integrated pan-cancer analysis to characterize the expression patterns, prognostic value, genetic alterations, and immunologic roles of transforming growth factor beta 1 (TGFB1) across diverse human cancer types VSports手机版. .

Methods: Bioinformatics analyses were conducted using multiple public databases including The Cancer Genome Atlas, Genotype-Tissue Expression, Clinical Proteomic Tumor Analysis Consortium, TIMER2, GEPIA2, cBioPortal, StringDB, and others V体育安卓版. Differential expression, survival, immune correlation, and protein interaction network analyses were performed. .

Results: TGFB1 was overexpressed in several tumor types compared with that in normal tissues. High TGFB1 expression was associated with an advanced stage and poorer prognosis in certain cancers V体育ios版. TGFB1 mutations occurred in 1. 3% of 10,967 cases surveyed. TGFB1 expression correlated with tumor-infiltrating immune cells and immunotherapy-related genes. .

Conclusions: This comprehensive multi-omics analysis revealed the complex expression and prognostic landscape of TGFB1 across cancers. TGFB1 is emerging as a potential immunotherapeutic target in certain contexts VSports最新版本. Further research should elucidate its multifaceted tumor-promoting and tumor-suppressive mechanisms. Our pan-cancer analysis provides new insights into TGFB1 as a prognostic biomarker and immunotherapeutic target in human cancers, and our findings may guide future preclinical and clinical investigations of TGFB1-directed therapies. .

Keywords: Transforming growth factor beta 1; gene mutation; immunotherapeutic target; multi-omic analysis; pan-cancer; prognosis V体育平台登录. .

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"V体育安卓版" Conflict of interest statement

Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Gene structure, protein structure, and conserved domain of transforming growth factor beta 1 (TGFB1). (a) Chromosome localization and secondary structure of the human TGFB1 protein. (b) The conserved domains of the TGFB1 protein structure. (c) The three-dimensional structure of the TGFB1 protein. (d) Conservation of the TGFB1 protein among different species. (e) The phylogenetic tree of TGFB1 in different species. (f) Location of the TGFB1 protein in cells and (g) TGFB1 protein sites in the Golgi apparatus of HEL (human erythroleukemic cell line) cells and extracellular secretion.
Figure 2.
Figure 2.
The expression levels of transforming growth factor beta 1 (TGFB1) in tumor tissues and normal tissues. (a) The mRNA expression levels of TGFB1 in a pan-cancer analysis using the TIMER database.Continued.*p < 0.05, **p < 0.01, ***p < 0.001. (b) Significantly different expression levels of TGFB1 between normal and tumor tissues and (c) Protein expression levels of TGFB1 in different tumor and normal tissues. TCGA, The Cancer Genome Atlas; GTEx, Genotype-Tissue Expression; CPTAC, Clinical Proteomic Tumor Analysis Consortium; ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 3.
Figure 3.
Association analysis of transforming growth factor beta 1 (TGFB1) expression with clinicopathological stages. (a–e) The association between TGFB1 expression and pathological clinical stage. (a) thyroid carcinoma (THCA), (b) kidney renal clear cell carcinoma (KIRC), (c) stomach adenocarcinoma (STAD), (d) bladder urothelial carcinoma (BLCA), (e) skin cutaneous melanoma (SKCM). (f–v) Correlations between TGFB1 expression and normal as well as different pathological clinical stages. (f) breast invasive carcinoma (BRCA), (g) esophageal carcinoma (ESCA), (h) THCA, (i) cholangiocarcinoma (CHOL), (j) head and neck squamous cell carcinoma (HNSC), (k) KIRC, (l) liver hepatocellular carcinoma (LIHC), (m) lung adenocarcinoma (LUAD), (n) lung squamous cell carcinoma (LUSC), (o) pancreatic adenocarcinoma (PAAD), (p) kidney chromophobe (KICH), (q) SKCM, (r) uterine corpus endometrial carcinoma (UCEC) and (s) colon adenocarcinoma (COAD), (t) STAD, (u) uveal melanoma (UVM) and (v) BLCA.
Figure 4.
Figure 4.
Correlation between transforming growth factor beta 1 (TGFB1) expression and survival prognosis of cancers. (a) Overall survival. (b) Disease-free survival. (c) Progression-free survival and (d) Disease-specific survival. ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian cancer; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 5.
Figure 5.
Transforming growth factor beta 1 (TGFB1) mutation landscape in various cancer types. (a) Summary of alteration frequency according to mutation type of TGFB1 in different tumors. (b) Mutation diagram of TGFB1 in pan-cancer analysis. (c) Some TGFB1 mutations are shown on the three-dimensional structure of the protein. (d–g) Correlation between TGFB1 mutation and survival prognosis in pan-cancer analysis. (d) Disease-free survival, (e) Disease-specific survival, (f) Overall survival and (g) Progression-free survival. BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; COAD, colon adenocarcinoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; PAAD, pancreatic adenocarcinoma; PRAD, prostate adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; OV, ovarian cancer.
Figure 6.
Figure 6.
Correlation analysis between transforming growth factor beta 1 (TGFB1) expression and immune infiltration of cancer-associated fibroblasts. ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian cancer; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 7.
Figure 7.
Correlation analysis between transforming growth factor beta 1 (TGFB1) expression and immune checkpoint inhibitor (ICI)-related genes, microsatellite instability (MSI), and tumor mutational burden (TMB). (a) The relationship of TGFB1 expression and ICI-related genes. Red indicates positive correlations; Blue indicates negative correlations. (b) The relationships of TGFB1 expression with CD274, PDCD1, CTLA4, LAG3 in liver hepatocellular carcinoma (LIHC). (c) Analysis of the correlation between TGFB1 expression and TMB (c) and MSI (d). ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 8.
Figure 8.
DNA methylation analysis of transforming growth factor beta 1 (TGFB1). (a–l) Differential DNA methylation levels of the TGFB1 promoter in various tumor types. (a) Testicular germ cell tumors (TGCT), (b) bladder urothelial carcinoma (BLCA), (c) thyroid carcinoma (THCA), (d) stomach adenocarcinoma (STAD), (e) pheochromocytoma and paraganglioma (PCPG), (f) cholangiocarcinoma (CHOL), (g) lung squamous cell carcinoma (LUSC), (h) kidney renal clear cell carcinoma (KIRC), (i) breast invasive carcinoma (BRCA), (j) prostate adenocarcinoma (PRAD), (k) colon adenocarcinoma (COAD), (l) uterine corpus endometrial carcinoma (UCEC). (m–v) The prognosis value of single CpG sites in TGFB1 in various tumor types. (m) Pancreatic adenocarcinoma (PAAD), (n) mesothelioma (MESO), (o) KIRC, (p) head and neck squamous cell carcinoma (HNSC), (q) LUSC, (r) acute myeloid leukemia (LAML), (s) BRCA, (t) adrenocortical carcinoma (ACC), (u) kidney renal papillary cell carcinoma (KIRP) and (v) uveal melanoma (UVM).
Figure 9.
Figure 9.
Protein–protein interaction (PPI) network analysis. (a) PPI network of transforming growth factor beta 1 (TGFB1) protein and TGFB1-related proteins based on the STRING database. (b) The gene–gene network analysis of TGFB1 and its related genes. (c) Network of enriched terms, colored according to p-value and (d) Network of enriched terms, colored according to cluster ID.
Figure 10.
Figure 10.
Correlation analysis of transforming growth factor beta 1 (TGFB1) and six main TGFB1-related genes. (a) Heatmap of selected TGFB1-related genes and cancer types. (b–g) Correlation between TGFB1 expression and selected target genes, including amyloid beta precursor protein (APP) (b), matrix metallopeptidase 2 (MMP2) (c), TGFB2 (d), TGFBR1 (e), TGFBR2 (f), thrombospondin 1 (THBS1) (g). ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian cancer; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 11.
Figure 11.
Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for transforming growth factor beta 1 (TGFB1) and its related genes. (a) GO analysis of TGFB1-related genes and (b) KEGG analysis of TGFB1-related genes.
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References

    1. Kocarnik JM, Compton K, Dean FE, et al.. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis for the Global Burden of Disease Study 2019. JAMA Oncol 2021; 8: 420–444. doi:10.1001/jamaoncol.2021.6987. - PMC - PubMed
    1. Soto-Perez-de-Celis E, De Glas NA, Hsu T, et al.. Global geriatric oncology: achievements and challenges. J Geriatr Oncol 2017; 8: 374–386. doi:10.1016/j.jgo.2017.06.001. - PubMed
    1. Feng RM, Zong YN, Cao SM, et al.. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond) 2019; 39: 22. doi:10.1186/s40880-019-0368-6. - PMC - PubMed
    1. Siegel RL, Miller KD, Fuchs HE, et al.. Cancer statistics, 2021. CA Cancer J Clin 2021; 71: 7–33. doi:10.3322/caac.21654. - PubMed
    1. Morrison AH, Byrne KT, Vonderheide RH. Immunotherapy and prevention of pancreatic cancer. Trends Cancer 2018; 4: 418–428. doi:10.1016/j.trecan.2018.04.001. - PMC - PubMed