POLQ identifies a better response subset to immunotherapy in muscle-invasive bladder cancer with high PD-L1.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38457207", "kind": "science-record", "revision": 2, "content_hash": "sha256:2958b8ea4b6a460101a0e27b762a3d11d6bcd3a04b097c44939c32f3c14b6baf", "created_at": "2026-11-01T19:20:23Z", "updated_at": "2026-11-01T21:32:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "POLQ identifies a better response subset to immunotherapy in muscle-invasive bladder cancer with high PD-L1.", "doi": "10.1002/cam4.6962", "pmid": "38457207", "authors": ["Ge Liu", "Kaifeng Jin", "Zhaopei Liu", "Xiaohe Su", "Ziyue Xu", "Bingyu Li", "Jingtong Xu", "Yuan Chang", "Yiwei Wang", "Yu Zhu", "Le Xu", "Jiejie Xu", "Zewei Wang", "Hailong Liu", "Weijuan Zhang"], "journal": "Cancer medicine", "year": 2024, "abstract": "BACKGROUND: Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy.\nMETHODS: A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo-cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC-108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment.\nRESULTS: We identified POLQhigh PD-L1high patients could benefit more from immunotherapy and platinum-based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules.\nCONCLUSIONS: The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD-L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.", "claims": [{"id": "claim-data-access", "statement": "Data and materials generated that are relevant to the results are included in this article. Other data are available from the corresponding author Prof. Zhang upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38457207", "locator": "sections[21] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Data and materials generated that are relevant to the results are included in this article. Other data are available from the corresponding author Prof. Zhang upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Furthermore, the combination of POLQ and PD‐L1 showed superior sensitivity to platinum‐based chemotherapy than POLQ or PD‐L1 alone, in the TCGA cohort (p = 0.012, Figure 3A), the ZSHS cohort (p = 0.001, Figure 3A), and the Neo‐cohort (p = 0.015, Figure 3A).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38457207", "locator": "sections[9] \"Prognostic value of POLQ alone or in combination with PD‐L1 to platinum‐based chemotherapy\" paragraph 2", "quote": "Furthermore, the combination of POLQ and PD‐L1 showed superior sensitivity to platinum‐based chemotherapy than POLQ or PD‐L1 alone, in the TCGA cohort (p = 0.012, Figure 3A), the ZSHS cohort (p = 0.001, Figure 3A), and the Neo‐cohort (p = 0.015, Figure 3A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Furthermore, the combination of POLQ and PD‐L1 showed superior sensitivity to platinum‐based chemotherapy than POLQ or PD‐L1 alone, in the TCGA cohort (p = 0.012, Figure 3A), the ZSHS cohort (p = 0.001, Figure 3A), and the Neo‐cohort (p = 0.015, Figure 3A).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38457207"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Antibodies used for immunostaining are listed in Table S5. Statistical analysis", "and assay methods The immunohistochemistry (IHC) was performed as described previously. 30 D"], "order_basis": "paper_text_order:1962", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["cox regression"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}