Construction of Endothelial Cell Signatures for Predicting the Diagnosis, Prognosis and Immunotherapy Response of Bladder Cancer Via Machine Learning

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2024 Mar 2

PMID 38429911

Authors

Yang Fu

Shanshan Sun

Du Shi

Jianbin Bi

Affiliations

Soon will be listed here.

Abstract

We subtyped bladder cancer (BC) patients based on the expression patterns of endothelial cell (EC) -related genes and constructed a diagnostic signature and an endothelial cell prognostic index (ECPI), which are useful for diagnosing BC patients, predicting the prognosis of BC and evaluating drug sensitivity. Differentially expressed genes in ECs were obtained from the Tumour Immune Single-Cell Hub database. Subsequently, a diagnostic signature, a tumour subtyping system and an ECPI were constructed using data from The Cancer Genome Atlas and Gene Expression Omnibus. Associations between the ECPI and the tumour microenvironment, drug sensitivity and biofunctions were assessed. The hub genes in the ECPI were identified as drug candidates by molecular docking. Subtype identification indicated that high EC levels were associated with a worse prognosis and immunosuppressive effect. The diagnostic signature and ECPI were used to effectively diagnose BC and accurately assess the prognosis of BC and drug sensitivity among patients. Three hub genes in the ECPI were extracted, and the three genes had the closest affinity for doxorubicin and curcumin. There was a close relationship between EC and BC. EC-related genes can help clinicians diagnose BC, predict the prognosis of BC and select effective drugs.

Citing Articles

Artificial intelligence application in the diagnosis and treatment of bladder cancer: advance, challenges, and opportunities.

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Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning.

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PMID: 38429911 PMC: 10907833. DOI: 10.1111/jcmm.18155.

References

Babjuk M, Burger M, Comperat E, Gontero P, Mostafid A, Palou J . European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update. Eur Urol. 2019; 76(5):639-657. DOI: 10.1016/j.eururo.2019.08.016. View

Chen Z, He S, Zhan Y, He A, Fang D, Gong Y . TGF-β-induced transgelin promotes bladder cancer metastasis by regulating epithelial-mesenchymal transition and invadopodia formation. EBioMedicine. 2019; 47:208-220. PMC: 6796540. DOI: 10.1016/j.ebiom.2019.08.012. View

Yin L, Wang Y . Extracellular vesicles derived from M2-polarized tumor-associated macrophages promote immune escape in ovarian cancer through NEAT1/miR-101-3p/ZEB1/PD-L1 axis. Cancer Immunol Immunother. 2022; 72(3):743-758. PMC: 10992138. DOI: 10.1007/s00262-022-03305-2. View

Luo Y, Zeng G, Wu S . Identification of Microenvironment-Related Prognostic Genes in Bladder Cancer Based on Gene Expression Profile. Front Genet. 2019; 10:1187. PMC: 6883806. DOI: 10.3389/fgene.2019.01187. View

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

Borentain P, Carmona S, Mathieu S, Jouve E, El-Battari A, Gerolami R . Inhibition of E-selectin expression on the surface of endothelial cells inhibits hepatocellular carcinoma growth by preventing tumor angiogenesis. Cancer Chemother Pharmacol. 2016; 77(4):847-56. DOI: 10.1007/s00280-016-3006-x. View

Chen W, Jiang J, Yu X, Xia W, Yu P, Wang K . Endothelial cells in colorectal cancer. World J Gastrointest Oncol. 2019; 11(11):946-956. PMC: 6883186. DOI: 10.4251/wjgo.v11.i11.946. View

Otsubo T, Hida Y, Ohga N, Sato H, Kai T, Matsuki Y . Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells. Cancer Sci. 2014; 105(5):560-7. PMC: 4317838. DOI: 10.1111/cas.12394. View

Sun D, Wang J, Han Y, Dong X, Ge J, Zheng R . TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res. 2020; 49(D1):D1420-D1430. PMC: 7778907. DOI: 10.1093/nar/gkaa1020. View

10.

Devarajan K . Nonnegative matrix factorization: an analytical and interpretive tool in computational biology. PLoS Comput Biol. 2008; 4(7):e1000029. PMC: 2447881. DOI: 10.1371/journal.pcbi.1000029. View

11.

Guillaume Z, Auvray M, Vano Y, Oudard S, Helley D, Mauge L . Renal Carcinoma and Angiogenesis: Therapeutic Target and Biomarkers of Response in Current Therapies. Cancers (Basel). 2022; 14(24). PMC: 9776425. DOI: 10.3390/cancers14246167. View

12.

Cumberbatch M, Jubber I, Black P, Esperto F, Figueroa J, Kamat A . Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018. Eur Urol. 2018; 74(6):784-795. DOI: 10.1016/j.eururo.2018.09.001. View

13.

Yeo J, Wasser M, Kumar P, Pan L, Poh S, Ally F . The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data. Nat Biotechnol. 2020; 38(6):679-684. DOI: 10.1038/s41587-020-0532-1. View

14.

Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W . Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013; 4:2612. PMC: 3826632. DOI: 10.1038/ncomms3612. View

15.

Yang T, Xiao H, Liu X, Wang Z, Zhang Q, Wei N . Vascular Normalization: A New Window Opened for Cancer Therapies. Front Oncol. 2021; 11:719836. PMC: 8406857. DOI: 10.3389/fonc.2021.719836. View

16.

Weygant N, Ge Y, Westphalen C, Ma W, Vega K . Role of the Microenvironment in Gastrointestinal Tumors. J Oncol. 2019; 2019:2153413. PMC: 6927018. DOI: 10.1155/2019/2153413. View

17.

Chang Y, Di Tomaso E, McDonald D, Jones R, Jain R, Munn L . Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A. 2000; 97(26):14608-13. PMC: 18966. DOI: 10.1073/pnas.97.26.14608. View

18.

Wronski P, Wronski S, Kurant M, Malinowski B, Wicinski M . Curcumin May Prevent Basement Membrane Disassembly by Matrix Metalloproteinases and Progression of the Bladder Cancer. Nutrients. 2022; 14(1). PMC: 8746354. DOI: 10.3390/nu14010032. View

19.

Fu Y, Sun S, Shi D, Bi J . Construction of endothelial cell signatures for predicting the diagnosis, prognosis and immunotherapy response of bladder cancer via machine learning. J Cell Mol Med. 2024; 28(6):e18155. PMC: 10907833. DOI: 10.1111/jcmm.18155. View

20.

Wang L, Saci A, Szabo P, Chasalow S, Castillo-Martin M, Domingo-Domenech J . EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat Commun. 2018; 9(1):3503. PMC: 6115401. DOI: 10.1038/s41467-018-05992-x. View