综合基因组和免疫组织化学分析预测基于孕酮的子宫内膜癌保生育治疗的预后和复发。

IF 2.8 4区 医学 Q3 ONCOLOGY
Technology in Cancer Research & Treatment Pub Date : 2025-01-01 Epub Date: 2025-06-27 DOI:10.1177/15330338251349972
Lin Yang, Yufei Nie, Hongyan Guo
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引用次数: 0

摘要

背景子宫内膜癌(EC)是一个独特的临床挑战。保留生育能力的治疗依赖于通过以黄体酮为基础的治疗实现完全缓解(CR)。我们试图研究分子分型和免疫组化(IHC)标志物在预测EC患者接受生育保留治疗的三个月治疗结果和复发方面的预后价值。方法回顾性分析2010年1月至2022年10月在我院保存石蜡包埋组织块,经宫腔镜手术及保守治疗的早期EC患者68例。基于TCGA分类的分子分型鉴定出低拷贝数(CNL)、高微卫星不稳定性(MSI-H)和高拷贝数(CNH)亚型。分析IHC标志物PTEN、PIK3CA、β-catenin、ARID1A、雌激素受体(ER)和孕激素受体(PR)与CR和复发的关系。转录组测序基因芯片用于研究三个月后达到或未达到CR的患者,一年内复发的患者以及两年内未复发的患者。然后将差异基因定位到KEGG通路,以探索黄体酮治疗疗效的潜在机制。结果经TCGA分子分型的68例患者中,CNL亚型65例(95.6%),MSI-H亚型2例(2.9%),CNH亚型1例(1.5%)。治疗3个月后,CNL亚型的CR率为75.4% (49/65),MSI-H亚型为50.0% (1/2),CNH亚型为0%(0/1)。在CNL亚型子宫内膜癌中,PTEN和PR高表达的个体更有可能在3个月后达到CR (P
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive Genomic and Immunohistochemical Profiling to Predict Prognosis and Recurrence in Fertility-Sparing Therapy Based on Progesterone for Endometrial Carcinoma.

BackgroundEndometrial carcinoma (EC) represents a unique clinical challenge. Fertility-sparing treatments rely on achieving complete response (CR) through progesterone-based therapy. We sought to investigate the prognostic value of molecular subtyping and immunohistochemical (IHC) markers in predicting three-month treatment outcomes and recurrence in EC patients undergoing fertility-sparing therapy.MethodsA retrospective cohort of 68 patients diagnosed with early-stage EC received hysteroscopic surgery and conservative treatment whose paraffin-embedded tissue blocks preserved in our hospital between Jan. 2010 and Oct. 2022 was evaluated. Molecular subtyping based on TCGA classification identified low copy-number (CNL), microsatellite instability-high (MSI-H), and copy-number high (CNH) subtypes. IHC markers, including PTEN, PIK3CA, β-catenin, ARID1A, estrogen receptor (ER), and progesterone receptor (PR) were analyzed for their association with CR and recurrence. Transcriptome sequencing gene chips were used to study patients who achieved or did not achieve CR after three months, those who experienced recurrence within one year, and those who did not recur within two years. Differential genes were then mapped to KEGG pathways to explore the underlying mechanisms of progesterone therapy efficacy.ResultsAmong the 68 patients classified through TCGA molecular typing, 65 cases (95.6%) were CNL subtype, two (2.9%) were MSI-H subtype, and one (1.5%) was CNH subtype. Following a three-month treatment, the CR rate for the CNL subtype was 75.4% (49/65), the MSI-H subtype was 50.0% (1/2), and the CNH subtype was 0% (0/1). In CNL subtype endometrial carcinoma, individuals with high PTEN and PR expression were more likely to achieve CR after three months (P < .05). Conversely, those with elevated CA199 levels and increased PIK3CA expression were more prone to recurrence after CR.ConclusionMSI-H and p53-mutant subtypes of endometrial carcinoma are not suitable for fertility preservation therapy. PTEN/PI3K-AKT-mTOR pathway activation contributes to reduced progesterone sensitivity, underscoring the need for targeted therapeutic strategies to improve patient outcomes.

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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
202
审稿时长
2 months
期刊介绍: Technology in Cancer Research & Treatment (TCRT) is a JCR-ranked, broad-spectrum, open access, peer-reviewed publication whose aim is to provide researchers and clinicians with a platform to share and discuss developments in the prevention, diagnosis, treatment, and monitoring of cancer.
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