Prognostic Significance and Immune Landscape of an Efferocytosis-Related Gene Signature in Bladder Cancer

被引:0
作者
Zheng, Fuchun [1 ,2 ]
Wang, Zhipeng [1 ,2 ]
Dong, Qianxi [1 ,2 ]
Li, Sheng [1 ,2 ]
Xiong, Situ [1 ,2 ]
Yuan, Yuyang [1 ,2 ]
Xu, Songhui [1 ,2 ]
Fu, Bin [1 ,2 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Urol, Nanchang 330000, Peoples R China
[2] Jiangxi Inst Urol, Nanchang, Jiangxi, Peoples R China
关键词
Bladder cancer; Efferocytosis; Prognosis; Risk signature; Immunotherapy; TUMOR PROGRESSION; MACROPHAGES; EXPRESSION; GRADE;
D O I
10.1007/s10528-024-10924-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bladder cancer poses a significant global health challenge, underscoring the imperative for precise prognostic instruments to advance patient care. Against the backdrop of efferocytosis's increasingly recognized role in cancer, this research endeavors to develop and authenticate a prognostic signature intricately linked to efferocytosis in bladder cancer. LASSO-COX regression analysis crafted an efferocytosis-related genes risk prognostic model, followed by the construction of a column chart. External validation sets confirmed the predictive accuracy of both the model and chart. Clinical, tumor microenvironment, drug sensitivity, and immunotherapy analyses were employed to comprehensively assess efferocytosis-related scores. The expression of TGFB3 key genes was validated via RT-PCR and western blotting. Further validation included Transwell, Wound healing, Colony formation, and EDU assays. We formulated and validated an efferocytosis-related genes risk model in bladder cancer, comprising 13 core genes. The risk model demonstrated autonomous prognostic significance in both univariate and multivariate Cox analyses. Following the multivariate analysis, we devised a nomogram. Moreover, by utilizing individual risk scores derived from this risk model, we successfully stratified patients into two discernible risk cohorts, unveiling noteworthy variances in immune infiltration profiles and responsiveness to immunotherapy. Notably, the model's key gene TGFB3 was validated through comprehensive experimental investigations, including Transwell assays for migration and invasion and Wound healing assays for motility on the T24 and BIU cell lines. This study has furnished innovative perspectives on an efferocytosis-related prognostic signature, elucidating the prognosis and immune milieu intricacies in patients with bladder cancer.
引用
收藏
页数:22
相关论文
共 45 条
  • [1] Gas6 expression and Tyrosine kinase Axl Sky receptors: Their relation with tumor stage and grade in patients with bladder cancer
    Akgul, Murat
    Baykan, Ozgur
    Cagman, Zeynep
    Ozyurek, Mustafa
    Tinay, Ilker
    Akbal, Cem
    Uras, Fikriye
    Turkeri, Levent
    [J]. ARCHIVIO ITALIANO DI UROLOGIA E ANDROLOGIA, 2021, 93 (02) : 148 - 152
  • [2] Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis
    Al Kafri, Nour
    Hafizi, Sassan
    [J]. CANCERS, 2019, 11 (12)
  • [3] Derivation and external validation of dendritic cell-related gene signatures for predicting prognosis and immunotherapy efficacy in bladder urothelial carcinoma
    An, Bingzheng
    Guo, Zhaoxin
    Wang, Junyan
    Zhang, Chen
    Zhang, Guanghao
    Yan, Lei
    [J]. FRONTIERS IN IMMUNOLOGY, 2022, 13
  • [4] Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial
    Balar, Arjun V.
    Galsky, Matthew D.
    Rosenberg, Jonathan E.
    Powles, Thomas
    Petrylak, Daniel P.
    Bellmunt, Joaquim
    Loriot, Yohann
    Necchi, Andrea
    Hoffman-Censits, Jean
    Perez-Gracia, Jose Luis
    Dawson, Nancy A.
    van der Heijden, Michiel S.
    Dreicer, Robert
    Srinivas, Sandy
    Retz, Margitta M.
    Joseph, Richard W.
    Drakaki, Alexandra
    Vaishampayan, Ulka N.
    Sridhar, Srikala S.
    Quinn, David I.
    Duran, Ignacio
    Shaffer, David R.
    Eigl, Bernhard J.
    Grivas, Petros D.
    Yu, Evan Y.
    Li, Shi
    Kadel, Edward E., III
    Boyd, Zachary
    Bourgon, Richard
    Hegde, Priti S.
    Mariathasan, Sanjeev
    Thastrom, AnnChristine
    Abidoye, Oyewale O.
    Fine, Gregg D.
    Bajorin, Dean F.
    [J]. LANCET, 2017, 389 (10064) : 67 - 76
  • [5] Efferocytosis and the Story of "Find Me," "Eat Me," and "Don't Eat Me" Signaling in the Tumor Microenvironment
    Banerjee, Hirendra Nath
    Bartlett, Victoria
    Krauss, Christopher
    Aurelius, Chelsea
    Johnston, Kayla
    Hedley, Joseph
    Verma, Mukesh
    [J]. TUMOR MICROENVIRONMENT: NOVEL CONCEPTS, 2021, 1329 : 153 - 162
  • [6] Bladder Cancer Exosomes Contain EDIL-3/Del1 and Facilitate Cancer Progression
    Beckham, Carla J.
    Olsen, Jayme
    Yin, Peng-Nien
    Wu, Chia-Hao
    Ting, Huei-Ju
    Hagen, Fred K.
    Scosyrev, Emelian
    Messing, Edward M.
    Lee, Yi-Fen
    [J]. JOURNAL OF UROLOGY, 2014, 192 (02) : 583 - 592
  • [7] Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
    Bellmunt, J.
    de Wit, R.
    Vaughn, D. J.
    Fradet, Y.
    Lee, J. -L.
    Fong, L.
    Vogelzang, N. J.
    Climent, M. A.
    Petrylak, D. P.
    Choueiri, T. K.
    Necchi, A.
    Gerritsen, W.
    Gurney, H.
    Quinn, D. I.
    Culine, S.
    Sternberg, C. N.
    Mai, Y.
    Poehlein, C. H.
    Perini, R. F.
    Bajorin, D. F.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) : 1015 - 1026
  • [8] Understanding the tumor immune microenvironment (TIME) for effective therapy
    Binnewies, Mikhail
    Roberts, Edward W.
    Kersten, Kelly
    Chan, Vincent
    Fearon, Douglas F.
    Merad, Miriam
    Coussens, Lisa M.
    Gabrilovich, Dmitry I.
    Ostrand-Rosenberg, Suzanne
    Hedrick, Catherine C.
    Vonderheide, Robert H.
    Pittet, Mikael J.
    Jain, Rakesh K.
    Zou, Weiping
    Howcroft, T. Kevin
    Woodhouse, Elisa C.
    Weinberg, Robert A.
    Krummel, Matthew F.
    [J]. NATURE MEDICINE, 2018, 24 (05) : 541 - 550
  • [9] Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study
    Catto, James W. F.
    Gordon, Kathryn
    Collinson, Michelle
    Poad, Heather
    Twiddy, Maureen
    Johnson, Mark
    Jain, Sunjay
    Chahal, Rohit
    Simms, Matt
    Dooldeniya, Mohantha
    Bell, Richard
    Koenig, Phillip
    Conroy, Samantha
    Goodwin, Louise
    Noon, Aidan P.
    Croft, Julie
    Brown, Julia M.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (03) : 202 - +
  • [10] Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells
    Chaudhary, Surbhi
    Patidar, Anil
    Dhiman, Asmita
    Chaubey, Gaurav Kumar
    Dilawari, Rahul
    Talukdar, Sharmila
    Modanwal, Radheshyam
    Raje, Manoj
    [J]. CELL DEATH & DISEASE, 2021, 12 (10)