Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

Chen, Yun; Han, Zaizhu; Feng, Yao; Ye, Qin; Hu, Jing; Guo, Yue; Feng, Yun‐Zhi

doi:10.3389/fmolb.2021.745649

Cited by 16 publications

(9 citation statements)

References 47 publications

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“…At the same time, in the research conducted by the Yun Chen, TGFBI was also elevated in various kinds of cancers (cholangiocarcinoma, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), GBM, head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and thyroid carcinoma), and it also showed a great value in the survival aspects. While for the clinical stage aspects, it was not very obvious for the KIRC [ 10 ]. In our results, although the OS and PFI show a strong correlation for the TMEM65, the predicting value of the gene for the clinical stage was more valuable for the early stage, especially for the BLCA and THCA.…”

Section: Discussionmentioning

confidence: 99%

“…Although TMEM65 correlated with some unimportant immune-related genes, TMEM65 showed some indicative significance for the three markers for certain kinds of cancers, and the meaning behind it implies significant correlation with the prognosis of the immune therapy. At the same time, the three markers (TMB, MSI, and NEO) also attracted lots of attention in the recent similar explorations [ 10 , 11 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

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[Retracted] Pan‐Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer

Song

Wang

Feng

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Introduction. Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein, which played important role in mediating autophagy, smooth muscle contraction, protein glycosylation, and immune response. In recent years, the interest had risen for exploring the function of the TMEM genes in the cancer fields. As a consequence, in our pan-cancer research of the TMEM65, we explored the function of the gene in kinds of database and tried to apply the finding in the clinical practice. Methods. In this research, we provide a comprehensive investigation of TMEM65 expression in a pan-cancer manner containing 33 cancer types. We evaluated the association of TMEM65 with the prognosis, immune infiltration, drug sensitivity analysis, GSVA enrichment analysis, TMB, MSI, NEO, and hotspot mechanisms. Results. TMEM65 was abnormally expressed in 24 types of cancers and showed correlation with the OS for 6 cancers and PFI for 9 cancers and kpI for 3 types. Moreover, the TME score, CD8 T effector, and immune checkpoint scoring systems showed a close correlation with the TMEM65. Moreover, TMEM65 was strongly correlated with some of the most common tumor-related genes and certain pathways (TGF beta signaling, TNFA signaling, hypoxia, pyroptosis, DNA repairing, autophagy, ferroptosis, and other related genes). Additionally, the TMEM65 showed correlations with the tumor mutational burden (TMB), microsatellite instability (MSI), NEO, and drug sensitivity. Finally, we confirmed several pathways by the GSEA and GSVA for the TMEM65 at the breast cancer aspects. Nomogram prediction model was also established for the breast tumors based on the TMEM65 level and other variables. Conclusion. Above all, the TMEM65 played important roles in predicting the prognosis of the cancers and correlated with the tumor immunity in the pan-cancer analysis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

[Retracted] Pan‐Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer

Song

Wang

Feng

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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“…In breast cancer, induction of EMT by overexpression of transcription factor SNAIL can render breast cancer cells resistant to the cytotoxic effect of CD8 + T cells through the induction of autophagy; and targeting an autophagy inducer (BECN1) restored CD8 + T mediated tumor cell lysis [ 62 ]. A recent pan cancer study indicated TGFBI as a prognostic marker in various cancers due to its involvement in various immune responses [ 63 ]. This is consistent with our analysis which showed a statistically significant positive association of infiltration of CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells with TGFB1 expression.…”

Section: Discussionmentioning

confidence: 99%

Platinum-resistance in epithelial ovarian cancer: an interplay of epithelial–mesenchymal transition interlinked with reprogrammed metabolism

Leung¹,

Price

Lokman

et al. 2022

J Transl Med

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Background Epithelial ovarian cancer is the most lethal gynaecological cancer worldwide. Chemotherapy resistance represents a significant clinical challenge and is the main reason for poor ovarian cancer prognosis. We identified novel expression of markers related to epithelial mesenchymal transitions (EMT) in a carboplatin resistant ovarian cancer cell line by proteomics. This was validated in the platinum resistant versus sensitive parental cell lines, as well as platinum resistant versus sensitive human ovarian cancer patient samples. The prognostic significance of the different proteomics-identified marker proteins in prognosis prediction on survival as well as their correlative association and influence on immune cell infiltration was determined by public domain data bases. Methods We explored the proteomic differences between carboplatin-sensitive OVCAR5 cells (parental) and their carboplatin-resistant counterpart, OVCAR5 CBPR cells. qPCR and western blots were performed to validate differentially expressed proteins at the mRNA and protein levels, respectively. Association of the identified proteins with epithelial–mesenchymal transition (EMT) prompted the investigation of cell motility. Cellular bioenergetics and proliferation were studied to delineate any biological adaptations that facilitate cancer progression. Expression of differentially expressed proteins was assessed in ovarian tumors obtained from platinum-sensitive (n = 15) versus platinum-resistant patients (n = 10), as well as matching tumors from patients at initial diagnosis and following relapse (n = 4). Kaplan–Meier plotter and Tumor Immune Estimation Resource (TIMER) databases were used to determine the prognostic significance and influence of the different proteomics-identified proteins on immune cell infiltration in the tumor microenvironment (TME). Results Our proteomics study identified 2422 proteins in both cell lines. Of these, 18 proteins were upregulated and 14 were downregulated by ≥ twofold (p < 0.05) in OVCAR5 CBPR cells. Gene ontology enrichment analysis amongst upregulated proteins revealed an overrepresentation of biological processes consistent with EMT in the resistant cell line. Enhanced mRNA and/or protein expression of the identified EMT modulators including ITGA2, TGFBI, AKR1B1, ITGAV, ITGA1, GFPT2, FLNA and G6PD were confirmed in OVCAR5 CBPR cells compared to parental OVCAR5 cell line. Consistent with the altered EMT profile, the OVCAR5 CBPR cells demonstrated enhanced migration and reduced proliferation, glycolysis, and oxidative phosphorylation. The upregulation of G6PD, AKR1B1, ITGAV, and TGFβ1 in OVCAR5 CBPR cells was also identified in the tumors of platinum-resistant compared to platinum-sensitive high grade serous ovarian cancer (HGSOC) patients. Matching tumors of relapsed versus newly diagnosed HGSOC patients also showed enhanced expression of AKR1B1, ITGAV, TGFβ1 and G6PD protein in relapsed tumors. Among the identified proteins, significant enhanced expression of GFPT2, FLNA, TGFBI (CDGG1), ITGA2 predicted unfavorable prognosis in ovarian cancer patients. Further analysis suggested that the expression of TGFBI to correlate positively with the expression of identified and validated proteins such as GFPT2, FLNA, G6PD, ITGAV, ITGA1 and ITGA2; and with the infiltration of CD8+ T cells, macrophages, neutrophils, and dendritic cells in the TME. Conclusions Our research demonstrates proteomic-based discovery of novel EMT-related markers with an altered metabolic profile in platinum-resistant versus sensitive ovarian cancer cell lines. The study also confirms the expression of selected identified markers in the tumors of platinum-resistant versus sensitive, and in matching relapsed versus newly diagnosed HGSOC patients. The study provides insights into the metabolic adaptation of EMT-induced carboplatin resistant cells that confers on them reduced proliferation to provide effective migratory advantage; and the role of some of these identified proteins in ovarian cancer prognosis. These observations warrant further investigation of these novel target proteins in platinum-resistant patients.

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“…PPT models enabled the unbiased identification of gene programs relevant to tissue dynamics along tumor development, and allowed us to assemble an epithelial-intrinsic Immune Exclusion Signature (IES) defined by expression of DDR1, TGFBI, PAK4, and DPEP1. This aggregated signature is highly informative, as these genes have been implicated separately as immune modulators but not always in the context of CRC 26,91,92,71 . DDR1 has been reported to align collagen fibers in a way that excludes T cells from the breast TME 27 .…”

Section: Discussionmentioning

confidence: 99%

Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors

Heiser

Simmons

Revetta

et al. 2023

Preprint

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Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Leveraging spatial molecular information to construct a phylogeographic map of tumor evolution can reveal individualized growth trajectories with diagnostic and therapeutic potential. Integrative analysis of spatial multi-omic data from 31 colorectal specimens revealed simultaneous microenvironmental and clonal alterations as a function of progression. Copy number variation served to re-stratify microsatellite stable and unstable tumors into chromosomally unstable (CIN+) and hypermutated (HM) classes. Phylogeographical maps classified tumors by their evolutionary dynamics, and clonal regions were placed along a global pseudotemporal progression trajectory. Cell-state discovery from a single-cell cohort revealed recurring epithelial gene signatures and infiltrating immune states in spatial transcriptomics. Charting these states along progression pseudotime, we observed a transition to immune exclusion in CIN+ tumors as characterized by a novel gene expression signature comprised of DDR1, TGFBI, PAK4, and DPEP1. We demonstrated how these genes and their protein products are key regulators of extracellular matrix components, are associated with lower cytotoxic immune infiltration, and show prog- nostic value in external cohorts. Through high-dimensional data integration, this atlas provides insights into co-evolution of tumors and their microenvironments, serving as a resource for stratification and targeted treatment of CRC.

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Pan-Cancer Analysis of the Associations of TGFBI Expression With Prognosis and Immune Characteristics

Cited by 16 publications

References 47 publications

[Retracted] Pan‐Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer

[Retracted] Pan‐Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer

Platinum-resistance in epithelial ovarian cancer: an interplay of epithelial–mesenchymal transition interlinked with reprogrammed metabolism

Molecular cartography uncovers evolutionary and microenvironmental dynamics in sporadic colorectal tumors

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