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一种基于细胞外基质蛋白的人工智能预测模型,用于卵巢浆液性腺癌的预后预测和免疫治疗评估。

An artificial intelligence prediction model based on extracellular matrix proteins for the prognostic prediction and immunotherapeutic evaluation of ovarian serous adenocarcinoma.

作者信息

Geng Tianxiang, Zheng Mengxue, Wang Yongfeng, Reseland Janne Elin, Samara Athina

机构信息

Department of Biomaterials, FUTURE, Center for Functional Tissue Reconstruction, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Laboratory of Reproductive Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Front Mol Biosci. 2023 Jun 14;10:1200354. doi: 10.3389/fmolb.2023.1200354. eCollection 2023.

Abstract

Ovarian Serous Adenocarcinoma is a malignant tumor originating from epithelial cells and one of the most common causes of death from gynecological cancers. The objective of this study was to develop a prediction model based on extracellular matrix proteins, using artificial intelligence techniques. The model aimed to aid healthcare professionals to predict the overall survival of patients with ovarian cancer (OC) and determine the efficacy of immunotherapy. The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection was used as the study dataset, whereas the TCGA-Pancancer dataset was used for validation. The prognostic importance of 1068 known extracellular matrix proteins for OC were determined by the Random Forest algorithm and the Lasso algorithm establishing the ECM risk score. Based on the gene expression data, the differences in mRNA abundance, tumour mutation burden (TMB) and tumour microenvironment (TME) between the high- and low-risk groups were assessed. Combining multiple artificial intelligence algorithms we were able to identify 15 key extracellular matrix genes, namely, , and confirm the validity of this ECM risk score for overall survival prediction. Several other parameters were identified as independent prognostic factors for OC by multivariate COX analysis. The analysis showed that thyroglobulin (TG) targeted immunotherapy was more effective in the high ECM risk score group, while the low ECM risk score group was more sensitive to the RYR2 gene-related immunotherapy. Additionally, the patients with low ECM risk scores had higher immune checkpoint gene expression and immunophenoscore levels and responded better to immunotherapy. The ECM risk score is an accurate tool to assess the patient's sensitivity to immunotherapy and forecast OC prognosis.

摘要

卵巢浆液性腺癌是一种起源于上皮细胞的恶性肿瘤,也是妇科癌症最常见的死亡原因之一。本研究的目的是利用人工智能技术,开发一种基于细胞外基质蛋白的预测模型。该模型旨在帮助医疗保健专业人员预测卵巢癌(OC)患者的总生存期,并确定免疫治疗的疗效。使用癌症基因组图谱卵巢癌(TCGA-OV)数据收集作为研究数据集,而TCGA泛癌数据集用于验证。通过随机森林算法和套索算法确定1068种已知细胞外基质蛋白对OC的预后重要性,建立ECM风险评分。基于基因表达数据,评估高风险组和低风险组之间mRNA丰度、肿瘤突变负担(TMB)和肿瘤微环境(TME)的差异。结合多种人工智能算法,我们能够识别出15个关键的细胞外基质基因,即,并证实该ECM风险评分对总生存期预测的有效性。通过多变量COX分析确定了其他几个参数作为OC的独立预后因素。分析表明,甲状腺球蛋白(TG)靶向免疫治疗在高ECM风险评分组中更有效,而低ECM风险评分组对RYR2基因相关免疫治疗更敏感。此外,低ECM风险评分的患者免疫检查点基因表达和免疫表型评分水平更高,对免疫治疗反应更好。ECM风险评分是评估患者对免疫治疗敏感性和预测OC预后的准确工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3108/10301747/72135fb34785/fmolb-10-1200354-g001.jpg

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