Identification and Validation of a Stromal EMT Related LncRNA Signature as a Potential Marker to Predict Bladder Cancer Outcome

被引：16

作者：

Du, YiHeng ^{[1
]}

Wang, Bo ^{[1
]}

Jiang, Xiang ^{[2
]}

Cao, Jin ^{[2
]}

Yu, Jiang ^{[1
]}

Wang, Yi ^{[1
]}

Wang, XiZhi ^{[1
]}

Liu, HaiTao ^{[3
]}

机构：

[1] Shanghai Jiao Tong Univ, Suzhou Kowloon Hosp, Dept Urol, Sch Med, Suzhou, Peoples R China

[2] Shanghai Jiao Tong Univ, Suzhou Kowloon Hosp, Dept Pathol, Sch Med, Suzhou, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Urol, Sch Med, Shanghai, Peoples R China

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

基金：

中国国家自然科学基金;

关键词：

bladder cancer; epithelial to mesenchymal transition; long non-coding RNAs; tumor microenvironment; immunosuppression; METASTASIS; IMMUNE; CELLS;

D O I：

10.3389/fonc.2021.620674

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Bladder cancer (BLCA) has become one of the most common malignant tumors in the genitourinary system. BLCA is one of the tumors considered suitable for immunotherapy because of the large proportion of immune cells in TME. Epithelial to mesenchymal transition (EMT) is closely related to tumor immunity through its crosstalk with immune cells. A recent study validated that EMT-related genes were mainly expressed by stromal cells and could influence immunotherapy responsiveness. Stromal EMT-related gene signature was also demonstrated to affect the prognosis of multiple tumors, including BLCA. To further explore the prognostic roles of stromal components, we performed a comprehensive analysis of LncRNAs closely associated with stromal EMT-related genes in the TCGA BLCA cohort. We identified a signature including five stromal EMT gene-related LncRNAs that showed significant prognostic value for BLCA patients. By the CIBERSORT and MCP-COUNTER algorithm, we found the signature was markedly correlated with infiltrated immune cells and stromal components of the tumor microenvironment, which may further influence patient's responsiveness to immune checkpoint blockade therapy. Through immunohistochemical analysis, we confirmed the correlation of the signature with macrophages M2 and CAFs. Meanwhile, key genes related to these LncRNAs, including VIM, MMP2, were also differentially expressed in the stromal components concerning the signature. Our research confirmed the prognostic and immune-associated role of stromal EMT-related LncRNAs. Meantime, we further confirmed that EMT-related genes were mainly expressed in stromal components. Targeting these LncRNAs as well as their related stromal EMT genes may provide potential therapeutic targets for BLCA immunotherapy and precision medicine.

引用

页数：15

共 39 条

[1] EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016 [J].

Babjuk, Marko ;

Boehle, Andreas ;

Burger, Maximilian ;

Capoun, Otakar ;

Cohen, Daniel ;

Comperat, Eva M. ;

Hernandez, Virginia ;

Kaasinen, Eero ;

Palou, Joan ;

Roupret, Morgan ;

van Rhijn, Bas W. G. ;

Shariat, Shahrokh F. ;

Soukup, Viktor ;

Sylvester, Richard J. ;

Zigeuner, Richard .

EUROPEAN UROLOGY, 2017, 71 (03) :447-461

[2] Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression [J].

Becht, Etienne ;

Giraldo, Nicolas A. ;

Lacroix, Laetitia ;

Buttard, Benedicte ;

Elarouci, Nabila ;

Petitprez, Florent ;

Selves, Janick ;

Laurent-Puig, Pierre ;

Sautes-Fridman, Catherine ;

Fridman, Wolf H. ;

de Reynies, Aurelien .

GENOME BIOLOGY, 2016, 17

[3] SNAIL1 action in tumor cells influences macrophage polarization and metastasis in breast cancer through altered GM-CSF secretion [J].

Brenot, Audrey ;

Knolhoff, Brett L. ;

DeNardo, David G. ;

Longmore, Gregory D. .

ONCOGENESIS, 2018, 7

[4] An EMT-related gene signature for the prognosis of human bladder cancer [J].

Cao, Rui ;

Yuan, Lushun ;

Ma, Bo ;

Wang, Gang ;

Qiu, Wei ;

Tian, Ye .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (01) :605-617

[5] Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles [J].

Cortes, Marlies ;

Sanchez-Moral, Lidia ;

de Barrios, Oriol ;

Fernandez-Acenero, Maria J. ;

Martinez-Campanario, M. C. ;

Esteve-Codina, Anna ;

Darling, Douglas S. ;

Gyorffy, Balazs ;

Lawrence, Toby ;

Dean, Douglas C. ;

Postigo, Antonio .

EMBO JOURNAL, 2017, 36 (22) :3336-3355

[6] Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples [J].

Costa, Vera L. ;

Henrique, Rui ;

Danielsen, Stine A. ;

Duarte-Pereira, Sara ;

Eknaes, Mette ;

Skotheim, Rolf I. ;

Rodrigues, Angelo ;

Magalhaes, Jose S. ;

Oliveira, Jorge ;

Lothe, Ragnhild A. ;

Teixeira, Manuel R. ;

Jeronimo, Carmen ;

Lind, Guro E. .

CLINICAL CANCER RESEARCH, 2010, 16 (23) :5842-5851

[7] Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion [J].

Dong, Peixin ;

Xiong, Ying ;

Yue, Junming ;

Hanley, Sharon J. B. ;

Watari, Hidemichi .

FRONTIERS IN ONCOLOGY, 2018, 8

[8] Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance [J].

Fischer, Kari R. ;

Durrans, Anna ;

Lee, Sharrell ;

Sheng, Jianting ;

Li, Fuhai ;

Wong, Stephen T. C. ;

Choi, Hyejin ;

El Rayes, Tina ;

Ryu, Seongho ;

Troeger, Juliane ;

Schwabe, Robert F. ;

Vahdat, Linda T. ;

Altorki, Nasser K. ;

Mittal, Vivek ;

Gao, Dingcheng .

NATURE, 2015, 527 (7579) :472-+

[9] Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1+ TAMs [J].

Gokyavuz, Betul ;

Gunaydin, Gurcan ;

Gedik, M. Emre ;

Kosemehmetoglu, Kemal ;

Karakoc, Derya ;

Ozgur, Figen ;

Guc, Dicle .

SCIENTIFIC REPORTS, 2019, 9 (1)

[10] Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance [J].

Gupta, Piyush B. ;

Pastushenko, Ievgenia ;

Skibinski, Adam ;

Blanpain, Cedric ;

Kuperwasser, Charlotte .

CELL STEM CELL, 2019, 24 (01) :65-78

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