为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Constructing a neural network model based on tumor-infiltrating lymphocytes (TILs) to predict the survival of hepatocellular carcinoma patients.
Constructing a neural network model based on tumor-infiltrating lymphocytes (TILs) to predict the survival of hepatocellular carcinoma patients.
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本研究共纳入 511 例患者,分为训练队列 331 例(2013 年 1 月至 2016 年 12 月来自青岛大学医院)和验证队列 180 例(TCGA)。结果揭示,TIL(肿瘤浸润淋巴细胞)(TILs)具有保护作用,并利用机器学习和神经网络技术成功预测了肝癌患者的生存风险。TNFSF4 的发现为免疫治疗提供了新的潜在靶点。
肝细胞癌(HCC)是全球最常见的原发性肝癌,早期病理诊断对于制定治疗方案至关重要。尽管在HCC患者治疗中病理学受到广泛关注,但病理图像中包含的大量信息常被忽视。
我们回顾性收集了(a)2013年1月至2016年12月期间青岛大学附属医院331例HCC患者的临床数据和病理切片图像,以及(b)来自癌症基因组图谱(TCGA)的180例HCC患者数据。经过数据筛选后,使用QuPath软件实现了对各种细胞类型的精确定量。通过Cox回归和神经网络模型,确定了与病理确诊HCC患者生存预后相关的关键因素,并筛选了潜在的治疗靶点。
我们的研究表明,TIL(肿瘤浸润淋巴细胞)(TILs)具有保护作用。我们通过机器学习量化了TILs指数,并构建了一个神经网络模型来预测患者的预后风险(训练集 ROC = 0.836,验证集 ROC 95% CI [0.7688-0.896]),模型预测的高危组和低危组在预后上存在显著差异(p = 2.6e-18,HR = 0.18,95% CI [0.12-0.27]),并且TNFSF4被确定为可能的免疫治疗靶点。
Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide, and early pathological diagnosis is crucial for formulating treatment plans. Despite the widespread attention to pathology in the treatment of HCC patients, a large amount of information contained in pathological images is often overlooked.
We retrospectively collected clinical data and pathological slide images from (a) 331 HCC patients at Qingdao University Affiliated Hospital between January 2013 and December 2016 and (b) 180 HCC patients from The Cancer Genome Atlas (TCGA). After data screening, precise quantification of various cell types was achieved using QuPath software. Key factors related to the survival prognosis of pathologically confirmed HCC patients were identified through Cox regression and neural network models, and potential therapeutic targets were screened.
Our study showed that tumour-infiltrating lymphocytes (TILs) had a protective effect. We quantified the TILs index by machine learning and built a neural network model to predict the prognostic risk of patients (ROC = 0.836 for training set ROC validation set). 95% CI [0.7688-0.896], and there was a significant difference in prognosis in the high-low risk group predicted by the model ( p = 2.6e-18, HR = 0.18, 95% CI [0.12-0.27], and TNFSF4 was identified as a possible immunotherapy target.
This study included a total of 511 patients, divided into a training cohort of 331 cases (from Qingdao University Hospital between January 2013 and December 2016) and a validation cohort of 180 cases (TCGA). The results revealed that tumor-infiltrating lymphocytes (TILs) have a protective effect and successfully predicted the survival risk of liver cancer patients using machine learning and neural network technology. The discovery of TNFSF4 provides a new potential target for immunotherapy.
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