Prognostic significance and identification of basement membrane-associated lncRNA in bladder cancer

Lixiang Feng; Jun Yang; Wei Zhang; Xiong Wang; Lili Li; Min Peng; Pengcheng Luo

doi:10.3389/fonc.2022.994703

Prognostic significance and identification of basement membrane-associated lncRNA in bladder cancer

Front Oncol. 2022 Oct 10:12:994703. doi: 10.3389/fonc.2022.994703. eCollection 2022.

Authors

Lixiang Feng¹, Jun Yang², Wei Zhang², Xiong Wang³, Lili Li⁴, Min Peng⁵, Pengcheng Luo¹

Affiliations

¹ Department of Urology, Wuhan Third Hospital, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
² Department of Urology, Wuhan Third Hospital, Wuhan, China.
³ Department of Pharmacy, Wuhan Third Hospital, Wuhan, China.
⁴ Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
⁵ Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Abstract

Based on the importance of basement membrane (BM) in cancer invasion and metastasis, we constructed a BM-associated lncRNA risk model to group bladder cancer (BCa) patients. Transcriptional and clinical data of BCa patients were downloaded from The Cancer Genome Atlas (TCGA), and the expressed genes of BM-related proteins were obtained from the BM-BASE database. We download the GSE133624 chip data from the GEO database as an external validation dataset. We screened for statistically different BM genes between tumors and adjacent normal tissues. Co-expression analysis of lncRNAs and differentially expressed BM genes was performed to identify BM-related lncRNAs. Then, differentially expressed BM-related lncRNAs (DEBMlncRNAs) between tumor and normal tissues were identified. Univariate/multivariate Cox regression analysis was performed to select lncRNAs for risk assessment. LASSO analysis was performed to build a prognostic model. We constructed a model containing 8 DEBMlncRNAs (AC004034.1, AL662797.1, NR2F1-AS1, SETBP1-DT, AC011503.2, AC093010.2, LINC00649 and LINC02321). The prognostic risk model accurately predicted the prognosis of BCa patients and revealed that tumor aggressiveness and distant metastasis were associated with higher risk scores. In this model, we constructed a nomogram to assist clinical decision-making based on clinicopathological characteristics such as age, T, and N. The model also showed good predictive power for the tumor microenvironment and mutational burden. We validated the expression of eight lncRNAs using the dataset GSE133624 and two human bladder cancer cell lines (5637, BIU-87) and examined the expression and cellular localization of LINC00649 and AC011503.2 using a human bladder cancer tissue chip. We found that knockdown of LINC00649 expression in 5637 cells promoted the proliferation of 5637 cells.Our eight DEBMlncRNA risk models provide new insights into predicting prognosis, tumor invasion, and metastasis in BCa patients.

Keywords: basement membrane; biomarkers; bladder cancer; lncRNAs; prognosis.