Long noncoding RNAs to predict postoperative recurrence in bladder cancer and to develop a new molecular classification system.

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

Biomarkers, Tumor/*genetics ; RNA, Long Noncoding/*genetics ; Urinary Bladder Neoplasms/*genetics; Biomarkers, Tumor/metabolism ; Biomarkers, Tumor/standards ; China ; Databases, Genetic ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Nomograms ; RNA, Long Noncoding/metabolism ; RNA, Long Noncoding/standards ; ROC Curve ; Survival Analysis ; Transcriptome/genetics ; Urinary Bladder Neoplasms/mortality ; Urinary Bladder Neoplasms/pathology

Background: Reliable molecular markers are much needed for early prediction of recurrence in muscle-invasive bladder cancer (MIBC) patients. We aimed to build a long-noncoding RNA (lncRNA) signature to improve recurrence prediction and lncRNA-based molecular classification of MIBC.
Methods: LncRNAs of 320 MIBC patients from the Cancer Genome Atlas (TCGA) database were analyzed, and a nomogram was established. A molecular classification system was created, and immunotherapy and chemotherapy response predictions, immune score analysis, immune infiltration analysis, and mutational data analysis were conducted. Survival analysis validation was also performed.
Results: An eight-lncRNA signature classifed the patients into high- and low-risk subgroups, and these groups had significantly different (disease-free survival) DFS. The ability of the eight-lncRNA signature to make an accurate prognosis was tested using a validation dataset from our samples. The nomogram achieved a C-index of 0.719 (95% CI, 0.674-0.764). Time-dependent receiver operating characteristic curve (ROC) analysis indicated the superior prognostic accuracy of nomograms for DFS prediction (0.76, 95% CI, 0.697-0.807). Further, the four clusters (median DFS = 11.8, 15.3, 17.9, and 18.9 months, respectively) showed a high frequency of TTN (cluster 1), fibroblast growth factor receptor-3 (cluster 2), TP53 (cluster 3), and TP53 mutations (cluster 4), respectively. They were enriched with M2 macrophages (cluster 1), CD8 ⁺ T cells (cluster 2), M0 macrophages (cluster 3), and M0 macrophages (cluster 4), respectively. Clusters 2 and 3 demonstrated potential sensitivity to immunotherapy and insensitivity to chemotherapy, whereas cluster 4 showed potential insensitivity to immunotherapy and sensitivity to chemotherapy.
Conclusions: The eight-lncRNA signature risk model may be a reliable prognostic signature for MIBC, which provides new insights into prediction of recurrence of MIBC. The model may help clinical decision and eventually benefit patients.
(© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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Keywords: biomarker; bladder cancer; lncRNA; molecular subtypes; recurrence

0 (Biomarkers, Tumor)
0 (RNA, Long Noncoding)

Date Created: 20211124 Date Completed: 20220315 Latest Revision: 20220315

20250114

PMC8729057

10.1002/cam4.4443

34816620