# Prediction of response to neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder cancer: role of immune-related gene expression **Authors:** Hadeer Mahmoud, Abeer M. Abd El-Aziz, Osama Ezzat, Hany Ibrahim Kenawy, Ahmed A. Shokeir PMC · DOI: 10.1007/s00262-025-04135-8 · Cancer Immunology, Immunotherapy : CII · 2025-07-30 ## TL;DR This study identifies immune-related genes that predict how well bladder cancer patients respond to a specific chemotherapy treatment. ## Contribution The study introduces immune-related gene expression as a novel predictor of chemotherapy response in muscle-invasive bladder cancer. ## Key findings - Higher GATA3 and IFN-γ gene expression correlates with better chemotherapy response in bladder cancer patients. - Lower METTL3 and ERCC2 gene expression is associated with improved response to neoadjuvant chemotherapy. - PD-L1 expression does not significantly differ between responders and non-responders. ## Abstract This prospective study aimed at investigating the role of immune-related gene expression (GATA3, METTL3, ERCC2, PD-L1 and IFN-γ) in the prediction of response to platinum-based neoadjuvant chemotherapy (NAC) in treatment of muscle-invasive bladder cancer (MIBC). A total of 112 patients received four cycles of systemic cisplatin-based NAC and then were subjected to radiological and histopathological evaluation through taking bladder biopsy before surgery. Quantitative real-time RT-PCR assessed GATA3, METTL3 and ERCC2 mRNA expression in tissue samples. Immunohistochemical (IHC) staining was done for GATA3, PD-L1 and IFN-γ in tissue samples. Out of the 112 patients, only 104 completed the proposed protocol of systemic NAC and were included in the final analysis. Out of 104 patients, 43 (41.4%) were responders and the remaining 61 patients (58.6%) were assigned as non-responders. GATA3 and IFN-γ expressions were significantly higher in tumor tissue of the responders compared to non-responders. METTL3 and ERCC2 expressions were significantly lower in tumor tissue of the responders compared to non-responders, whereas, PD-L1 staining showed no significant difference between both groups. Our study suggests that GATA3, METTL3, ERCC2, and IFN-γ could serve as predictive biomarkers for NAC response in MIBC patients. Higher GATA3 and IFN-γ along with lower METTL3 and ERCC2 levels are positively correlated with better response to NAC. The online version contains supplementary material available at 10.1007/s00262-025-04135-8. ## Linked entities - **Genes:** GATA3 (GATA binding protein 3) [NCBI Gene 2625], METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339], ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit) [NCBI Gene 2068], CD274 (CD274 molecule) [NCBI Gene 29126], IFNG (interferon gamma) [NCBI Gene 3458] - **Chemicals:** cisplatin (PubChem CID 5460033) ## Full-text entities - **Genes:** GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit) [NCBI Gene 2068] {aka COFS2, CXPD, EM9, TFIIH, TTD, TTD1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit) [NCBI Gene 56339] {aka IME4, M6A, MT-A70, Spo8, hMETTL3}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CXCL11 (C-X-C motif chemokine ligand 11) [NCBI Gene 6373] {aka H174, I-TAC, IP-9, IP9, SCYB11, SCYB9B} - **Diseases:** bladder tumorigenesis (MESH:D063646), NAC (MESH:D000084202), MIBC (MESH:D000093284), toxicity (MESH:D064420), metastasis (MESH:D009362), disease (MESH:D004194), Immunogenic tumors (MESH:D009369), inflammatory (MESH:D007249), BC (MESH:D001749) - **Chemicals:** xylene (MESH:D014992), SYBR green (MESH:C098022), Hematoxylin (MESH:D006416), TRIZOL (MESH:C411644), Paraffin (MESH:D010232), methanol (MESH:D000432), Formalin (MESH:D005557), hydrogen peroxide (MESH:D006861), Biotin (MESH:D001710), DAB (-), platinum (MESH:D010984), H&E (MESH:D006371), alcohol (MESH:D000438), eosin (MESH:D004801), Cisplatin (MESH:D002945), m6A (MESH:C005955), Gemcitabine (MESH:D000093542), PBS (MESH:D007854), water (MESH:D014867) - **Species:** Homo sapiens (human, species) [taxon 9606] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12311079/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12311079/full.md --- Source: https://tomesphere.com/paper/PMC12311079