ArticleCancer chemotherapy and pharmacology2025
Clinical relevance of Nectin-4 downregulation and biological changes caused by cytotoxic chemotherapy in bladder cancer.
Article in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- FGFR3 Alterations and Nectin-4 Expression as Therapeutic Biomarkers in Bladder Cancer: A Systematic Review and Single-Arm Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Nectin-4 immunohistochemistry distinguishes urothelial carcinoma in situ from reactive urothelium.Virchows Archiv : an international journal of pathology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
introductionMechanism underlying resistance to enfortumab vedotin (EV) and prognostication of Nectin-4 expression in muscle-invasive bladder cancer (MIBC) remains unclear.
methodsWe generated gemcitabine-resistant HT-1376 and cisplatin-resistant HT-1376 cells generated from parental HT1376 cells (derived from MIBC). Transcriptome analysis was conducted to explore the biological function of differentially expressed genes detected in chemoresistant HT-1376 cells compared to parental HT-1376. In 70 patients with MIBC undergoing radical cystectomy, unsupervised hierarchical clustering was performed using immunohistochemical staining pattern with GATA3, KRT20, KRT5/6, KRT14, and Nectin-4 expression derived from the gene expression-based Nectin-4-modified NanoString molecular classification: Luminal-Nec4-High, Luminal-Nec4-Low, Basal-Nec4-High, and Basal-Nec4-Low subgroups.
resultsWe found significant downregulation of Nectin-4 expression along with epithelial-to-mesenchymal transition in chemoresistant HT-1376 cells. Exogenous expression of NECTIN4 in chemoresistant HT-1376 cells partially restored sensitivity to EV. RNA seq identified differentially expressed genes, including Nectin-4 and small proline-rich proteins, downregulated in chemoresistant HT-1376 cells. Over-representation analysis using GO and KEGG revealed upregulation of gene sets enriched for ribosome biogenesis-related pathways in chemoresistant HT-1376 cells. Nectin-4-modified molecular subtype resulted in better stratification of survival-the Luminal-Nec4-High subgroup had the best and the Basal-Nec4-Low subgroup had the worst prognosis. Comparing molecular subtypes of MIBC cells between transurethral resection specimens and matched radical cystectomy specimens revealed that 43% of neoadjuvant chemotherapy-treated patients with luminal subtype tumors showed a marked shift to the basal subtype in the cystectomy specimens.
conclusionThe clinical utility of Nection-4, associated molecules, and Nectin-4-modified molecular subtype need to be studied for better management strategies for MIBC.
Indexed as
Identifiers
40560260What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.