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33 对免疫相关基因对可预测肝细胞癌的临床结局。

A signature of 33 immune-related gene pairs predicts clinical outcome in hepatocellular carcinoma.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, Henan, China.

出版信息

Cancer Med. 2020 Apr;9(8):2868-2878. doi: 10.1002/cam4.2921. Epub 2020 Feb 18.

Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) has become the second most common tumor type that contributes to cancer-related death worldwide. The study aimed to establish a robust immune-related gene pair (IRGP) signature for predicting the prognosis of HCC patients.

METHODS

Two RNA-seq datasets (The Cancer Genome Atlas Program and International Cancer Genome Consortium) and one microarray dataset (GSE14520) were included in this study. We used a series of immune-related genes from the ImmPort database to construct gene pairs. Lasso penalized Cox proportional hazards regression was employed to develop the best prognostic signature. We assigned patients into two groups with low immune risk and high immune risk. Then, the prognostic ability of the signature was evaluated by a log-rank test and a Cox proportional hazards regression model.

RESULTS

After 1000 iterations, the 33-immune gene pair model obtained the highest frequency. As a result, we chose the 33 immune gene pairs to establish the immune-related prognostic signature. As we expected, the immune-related signature accurately predicted the prognosis of HCC patients, and high-risk groups showed poor prognosis in the training datasets and testing datasets as well as in the validation datasets. Furthermore, the immune-related gene pair (IRGP) signature also showed higher predictive accuracy than three existing prognostic signatures.

CONCLUSION

Our prognostic signature, which reflects the link between the immune microenvironment and HCC patient outcome, is promising for prognosis prediction in HCC.

摘要

目的

肝细胞癌(HCC)已成为导致全球癌症相关死亡的第二大常见肿瘤类型。本研究旨在建立一个稳健的免疫相关基因对(IRGP)signature,用于预测 HCC 患者的预后。

方法

本研究纳入了两个 RNA-seq 数据集(癌症基因组图谱计划和国际癌症基因组联盟)和一个微阵列数据集(GSE14520)。我们使用 ImmPort 数据库中的一系列免疫相关基因来构建基因对。使用 Lasso 惩罚 Cox 比例风险回归来开发最佳预后 signature。我们将患者分为低免疫风险和高免疫风险两组。然后,通过对数秩检验和 Cox 比例风险回归模型评估 signature 的预后能力。

结果

经过 1000 次迭代,获得了最高频率的 33-免疫基因对模型。因此,我们选择了 33 个免疫基因对来建立免疫相关的预后 signature。正如我们所预期的那样,该免疫相关 signature 能够准确预测 HCC 患者的预后,高风险组在训练数据集、测试数据集和验证数据集中均表现出较差的预后。此外,免疫相关基因对(IRGP)signature 也显示出比三种现有预后 signature 更高的预测准确性。

结论

我们的预后 signature 反映了免疫微环境与 HCC 患者结局之间的联系,有望用于 HCC 的预后预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd52/7163092/39a750cbfd33/CAM4-9-2868-g001.jpg

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