Back to all available

Neuro-immune–related gene signatures define molecular subtypes and prognostic score in bladder cancer with SERPINE2 as a potential therapeutic target

bioinformatics
immunology
oncology
urology

Abstract

Neuro-immune interactions are critical in cancer, yet their molecular features in bladder cancer remain unclear. We analyzed transcriptomic data from TCGA and UCSC Xena to investigate the expression profiles and molecular subtypes of neuro-immune–related genes, and constructed a neuro-immune–related score (NAS) model. Single-cell transcriptomic data were integrated to explore the immune microenvironmental features, and functional validation was performed by knocking down SERPINE2 with shRNA in T24 cells. The results showed that six core genes (SERPINE2, NXPH4, SERPINB2, C2orf40, SERPINB12, SERPINB10) were identified to stratify patients into high- and low-risk groups, with robust predictive power across clinical subgroups and validation cohorts. Single-cell RNA-seq data revealed significant NAS heterogeneity among cell populations. The NAS-high state was enriched in TGFβ, EGF, and FGF signaling with activation of EZH2 and SMARCA4, while the NAS-low state showed immune-regulatory features. Functional assays confirmed that SERPINE2 knockdown suppressed proliferation, migration, and invasion, while increasing apoptosis of T24 cells, highlighting its oncogenic role. Moreover, GWAS suggested that genetic variants in SERPINE2 and related genes may increase bladder cancer susceptibility. Collectively, neuro-immune–related genes contribute to tumor progression and immune remodeling in bladder cancer. The NAS model provides a promising prognostic tool, while SERPINE2 emerges as a potential therapeutic target.
Ask to review this manuscript

Notes for potential reviewers

  • Volunteering is not a guarantee that you will be asked to review. There are many reasons: reviewers must be qualified, there should be no conflicts of interest, a minimum of two reviewers have already accepted an invitation, etc.
  • This is NOT OPEN peer review. The review is single-blind, and all recommendations are sent privately to the Academic Editor handling the manuscript. All reviews are published and reviewers can choose to sign their reviews.
  • What happens after volunteering? It may be a few days before you receive an invitation to review with further instructions. You will need to accept the invitation to then become an official referee for the manuscript. If you do not receive an invitation it is for one of many possible reasons as noted above.
  • PeerJ does not judge submissions based on subjective measures such as novelty, impact or degree of advance. Effectively, reviewers are asked to comment on whether or not the submission is scientifically and technically sound and therefore deserves to join the scientific literature. Our Peer Review criteria can be found on the "Editorial Criteria" page - reviewers are specifically asked to comment on 3 broad areas: "Basic Reporting", "Experimental Design" and "Validity of the Findings".
  • Reviewers are expected to comment in a timely, professional, and constructive manner.
  • Until the article is published, reviewers must regard all information relating to the submission as strictly confidential.
  • When submitting a review, reviewers are given the option to "sign" their review (i.e. to associate their name with their comments). Otherwise, all review comments remain anonymous.
  • All reviews of published articles are published. This includes manuscript files, peer review comments, author rebuttals and revised materials.
  • Each time a decision is made by the Academic Editor, each reviewer will receive a copy of the Decision Letter (which will include the comments of all reviewers).

If you have any questions about submitting your review, please email us at [email protected].