{"id":445,"title":"Integrative Pan-Cancer Multi-Omics Analysis Reveals POLQ as a Prognostic Biomarker and Immunotherapeutic Target in Uterine Corpus Endometrial Carcinoma","title_zh":"泛癌多组学分析揭示POLQ为子宫体子宫内膜癌的预后标志物与免疫治疗靶点","url":"https://doi.org/10.21203/rs.3.rs-11107769/v1","doi":"10.21203/rs.3.rs-11107769/v1","pmid":null,"journal":"Research Square","kind":"preprint","lang":"en","published_at":"2026-11-03T00:00:00+00:00","fetched_at":"2026-11-08T03:44:14+00:00","authors":["Du B","Wang C","Lv Y","Wang Q","Wang F","Li J","Gao H","Chang R","Li H"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":8.0,"hits":["endometrial","uterine"]},{"slug":"omics-methods","score":4.0,"hits":["multi-omics"]},{"slug":"repro-immunology","score":1.0,"hits":["immunotherapy"]}],"topic_score":8.0,"preference_score":10.0,"preference_labels":["多组学整合分析（任意生殖对象）"],"llm_score":68.0,"final_score":78.0,"score_dims":{"novelty":60,"rigor":62,"impact":58,"relevance":55,"translation":60},"recommend_reason":"多组学整合较系统，并给出POLQ在子宫内膜癌中的免疫与细胞周期机制线索，对内膜癌分子分型与靶向治疗选题有参考价值；但为公共数据库二次分析、以分子对接等生信预测为主，缺乏实验验证，且与辅助生殖核心流程距离较远。","keywords":["POLQ","子宫内膜癌","泛癌多组学","肿瘤免疫微环境","预后标志物","分子对接"],"selected":1,"story_id":120,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"europepmc-preprints","source_name":"Europe PMC · 预印本（领域内）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"research-square","journal_tier":"standard","journal_if":null,"is_mock":false,"summary_zh":"研究利用TCGA、GTEx、cBioPortal、TIMER2.0与GSCA等多组学数据，对DNA聚合酶θ（POLQ）进行泛癌表达、突变、预后与免疫特征分析，并结合药敏相关性与分子对接预测长春新碱、紫杉醇、多西他赛与POLQ蛋白的潜在结合。结果显示POLQ在多数恶性肿瘤中高表达，与晚期及不良生存相关，基因扩增为其上调驱动因素；其表达与免疫细胞浸润、肿瘤突变负荷及微卫星不稳定性显著相关。在子宫内膜癌中，高表达POLQ激活DNA复制、细胞周期及ATR依赖的DNA损伤通路。结论认为POLQ是泛癌预后与治疗标志物，支持以其为靶点的精准免疫治疗，尤其针对子宫内膜癌。","summary":"Abstract DNA polymerase theta (POLQ) mediates microhomology-mediated end joining and represents a synthetic lethal target for homologous recombination deficient cancers, yet its pan-cancer clinical, immunoregulatory and predictive functions are poorly defined. Multi-omics data from TCGA, GTEx, cBioPortal, TIMER2.0 and GSCA were used for pan-cancer profiling of POLQ expression, mutations, prognosis, immune signatures. Drug sensitivity correlation analysis together with in silico molecular docking simulations were applied to predict potential binding between POLQ and candidate therapeutic agents. Differential gene expression analysis and functional enrichment were further investigated in uterine corpus endometrial carcinoma (UCEC). POLQ was overexpressed in most malignancies, associated with advanced stages and poor survival. Gene amplification drove its upregulation. POLQ expression showed significant correlations with immune cell infiltration, tumor mutation burden, and microsatellite instability. The strong negative correlations between POLQ expression and responses to multiple chemotherapeutic agents, with molecular docking predicted potential direct interactions between vincristine, paclitaxel, docetaxel and the POLQ protein. In UCEC, high POLQ activated DNA replication, cell cycle and ATR-dependent DNA damage pathways. POLQ is a pan-cancer prognostic and therapeutic biomarker. In UCEC, it accelerates tumor progression via DNA damage and cell cycle dysregulation and reshapes immune microenvironment, supporting POLQ-targeted precision immunotherapy especially for endometrial cancer.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}