Anoikis-Associated Signatures Predict Prognosis and Immune Response in Bladder Cancer

Abstract

Objective: Anoikis is a type of programmed cell death that occurs in normal epithelial and endothelial cells. However, the specific role of anoikis regulators (ANRs) in bladder cancer (BLCA) remains unknown. Therefore, the objective of this study was to find subgroups that could identify different levels of anoikis resistance in BLCA and construct an anoikis scoring system to assess prognosis. Method: By obtaining ANRs from public datasets, subgroups of BLCA with varying degrees of anoikis resistance were identified, and risk was determined. Result: ANRs affects the occurrence and prognosis of BLCA and can be predicted by establishing risk models. Conclusion: The anoikis scoring system and anoikis-associated risk profiles may help develop more effective and personalized treatment strategies for BLCA patients.

Plain language summary

This study investigates lncRNAs’ role in predicting bladder cancer patient prognosis and immune response. Anoikis is a key focus. Highly variable genes are identified, suggesting personalized treatment strategies. An anoikis scoring system aids clinicians.

Tweetable abstract

Anoikis is a type of programmed cell death that occurs in normal epithelial and endothelial cells and lead to the development of malignancies and drug resistance. Therefore, we aimed to determine its role in bladder cancer.

Keywords::

• anoikis
• bladder cancer
• immunotherapy
• prognosis
• tumor microenvironment

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0240

Conceptualization: YQ Shu; methodology: YQ Shu and XZ Wang; software: XZ Wang and ZY Wang; validation: XZ Wang, ZY Wang and Q Wei; formal analysis: XZ Wang, ZY Wang, Q Wei and HY Wang; data curation: XZ Wang; writing – original draft preparation: XZ Wang; writing – review&editing: XZ Wang, ZY Wang, Q Wei, HY Wang and YQ Shu; visualization: XZ Wang; supervision: YQ Shu; project administration: YQ Shu; funding acquisition: YQ Shu.

Acknowledgments

The authors thank all staff members of the Department of Oncology and Jiangsu Key Lab of Cancer Biomarkers, the First Affiliated Hospital of Nanjing Medical University (Nanjing, China), and also the National Natural Science Foundation of China for their support.

Financial disclosure

This research was funded by the National Natural Science Foundation of China (grants. 82172889 and 82203010) and by the Clinical Frontier Technology of Jiangsu Provincial Department of Science and Technology in China (grant BE2020783).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University, China (approval no. 2021-SRFA-016 on 1 March 2021).

Informed consent was obtained from all patients involved in this study, and ethics approval was granted. The authors collected eight bladder cancer tissue samples and matched adjacent nontumor tissue samples from routine surgeries at the First Affiliated Hospital of Nanjing Medical University in China. The clinical registration number for this study is NCT04658862.

Data sharing statement

The authors downloaded gene expression files and information on clinical characteristics of patients with BLCA from the TCGA (https://portal.gdc.cancer.gov/) BLCA cohort and the GSE31684 dataset from GEO (www.ncbi.nlm.nih.gov/geo/). Expression data and clinical annotations were also obtained for the IMvigor210 phase II trial study (http://research-pub.gene.com/IMvigor210CoreBiologies). All expression data were standardized to transcripts per million. Single-nucleotide mutation annotation and copy number variation data were obtained from the TCGA-BLCA cohort. A gene set containing 19 ANRs was obtained from the GO Biological Process Annotations dataset (Gene Ontology, GO_2000209).