Common immunological and prognostic features of lung and bladder cancer via smoking-related genes: PRR11 gene as potential immunotherapeutic target

Sep 21, 2026

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Smoking is a well-established risk factor for non-small-cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA), yet a unifying prognostic marker from smoking-related genes that also links to immune checkpoint therapy has remained unclear. This study identified smoking-related differential genes in NSCLC and BLCA, assessed their roles in patient prognosis and immune checkpoint therapy using subgroup analyses, and highlighted PRR11 as a crucial prognostic gene in both cancers. Co-expressed PRR11 genes were used to build a prognostic model, validated across cancers. Molecular docking and tissue microarray experiments, together with miRNA analysis, supported a PRR11–SPDL1 axis influencing PDL1 and immunotherapeutic efficacy via stemness modulation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Smoking as a risk factor for lung and bladder cancer

Immune checkpoint therapy and smoking-associated immune changes

Abstract

Study aims and approach

PRR11, prognostic modeling, and immunotherapy relevance

Key findings highlighted in the abstract

DOI: 10. 1111/jcmm.18384 OR I G I NAL ART I C L E Common immunological and prognostic features of lung and bladder cancer via smoking-related genes: PRR11 gene as potential immunotherapeutic target YaXuan Wang1 | HaiXia Zhu2 | Lu Zhang1 | JiaXing He1 | Ji Bo1 | JianShe Wang1 | BeiChen Ding1 | MingHua Ren1 1Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China 2Department of Central Laboratory, Affiliated Tumor Hospital of Nantong University & Nantong Tumor Hospital, Nantong, China Correspondence BeiChen Ding and MingHua Ren, Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Email: [dingbeichen@hrbmu.edu.cn](dingbeichen@hrbmu.edu.cn) and [002051@hrbmu.edu.cn](002051@hrbmu.edu.cn) Funding information National Natural Science Foundation of China, Grant/Award Number: 82002680; Natural Science Foundation of Heilongjiang Province, Grant/Award Number: LH2019H030 Abstract Smoking is a well-known risk factor for non-small-cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA) . Despite this, there has been no investigation into a prognostic marker based on smoking-related genes that could universally predict prognosis in these cancers and correlate with immune checkpoint therapy. This study aimed to identify smoking-related differential genes in NSCLC and BLCA, analyse their roles in patient prognosis and immune checkpoint therapy through subgroup analyses, and shed light on PRR11 as a crucial prognostic gene in both cancers. By examining PRR11 co-expressed genes, a prognostic model was constructed and its impact on immunotherapy for NSCLC and BLCA was evaluated. Molecular docking and tissue microarray analyses were conducted to explore the correlation between PRR11 and its reciprocal gene SPDL1 . Additionally, miRNAs associated with PRR11 were analysed. The study confirmed a strong link between smoking-related genes, prognosis, and immune checkpoint therapy in NSCLC and BLCA. PRR11 was identified as a key smoking-associated gene that influences the efficacy of immune checkpoint therapy by modulating the stemness of these cancers. A prognostic model based on PRR11 co-expressed genes in BLCA was established and its prognostic value was validated in NSCLC. Furthermore, it was found that PRR11 regulates PDL1 via SPDL1, impacting immunotherapeutic efficacy in both cancers. The involvement of hsa-miR-200b-3pin the regulation of SPDL1 expression by PRR11 was also highlighted. Overall, the study elucidates that PRR11 modulates patient immunotherapy by influencing PDL1 expression through its interaction with SPDL1, with potential upstream regulation by hsa-miR-200b-3p. K E Y WO R D S BLCA, immune checkpoint inhibitor, NSCLC, prognosis, PRR11 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. J Cell Mol Med. 2024;28:e18384 . [https://doi.org/10.1111/jcmm.18384](https://doi.org/10.1111/jcmm.18384) [wileyonlinelibrary.com/journal/jcmm](wileyonlinelibrary.com/journal/jcmm) 1 of 18 1 | INTRODUCTION Cancer is the second most prevalent reason behind global mortality. The biology of different cancer types is greatly impacted by exposure to risk factors.1 Understanding modifiable risk factors is crucial in managing cancer progression, and tobacco use and exposure to second-hand smoke stand out as major contributors to this ailment. As outlined by the World Health Organization (WHO), approximately 1.1billion people across the globe engage in tobacco consumption, resulting in an estimated 6 million deaths linked to tobacco every year.2 Cigarettes encompass deleterious constituents, including nicotine, acrolein

FAQs

What cancers and risk factor are examined in the study?

The study focuses on non-small-cell lung cancer (NSCLC) and bladder urothelial carcinoma (BLCA) and centers on smoking as a major risk factor.

How does the study evaluate prognosis and immune checkpoint therapy?

It identifies smoking-related differential genes, performs subgroup analyses to connect gene roles with prognosis and immune checkpoint therapy, and constructs prognostic models based on PRR11 co-expressed genes.

Why is PRR11 proposed as a potential immunotherapeutic target?

The study reports that PRR11 influences immunotherapy efficacy by modulating cancer stemness and by regulating PDL1 through an interaction involving SPDL1; hsa-miR-200b-3p is implicated as upstream regulation.

Sep 21, 2026

Uploaded by Aurora