月光基因 ALAD 低表达与肝癌预后不良相关。

Low expression of moonlight gene ALAD is correlated with poor prognosis in hepatocellular carcinoma.

机构信息

Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.

Clinical Pharmacy Center, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China; Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.

出版信息

Gene. 2022 May 30;825:146437. doi: 10.1016/j.gene.2022.146437. Epub 2022 Mar 19.

DOI:10.1016/j.gene.2022.146437

PMID:35318110

Abstract

BACKGROUND

Moonlighting genes may involve in the progression of hepatocellular carcinoma (HCC), and the establishment of a prognostic signature based on moonlighting genes may help predict the prognosis of HCC patients.

METHODS

This study aimed to construct a prognostic signature based on moonlighting genes in HCC and determine whether there is a correlation with tumor microenvironment or immune responses. Then we used HCC cell lines and an HCC cDNA microarray to illuminate the role of moonlighting gene in prognosis of HCC.

RESULTS

We constructed an original prognostic signature based on eight moonlighting genes (ABCB1, S100A9, NCL, PRDX6, ALAD, YBX1, POU2F1, RPL5) with strong prognosis prediction capability. The prognostic signature may demonstrate the immune status of patients with HCC, because high-risk subgroups had significantly higher scores for regulatory T cells, dendritic cells, T follicular helper cells, macrophages, and major histocompatibility complex-I, and different expression levels of immune checkpoint molecules. Importantly, patients in the high-risk subgroup exhibited higher tumor immune dysfunction and exclusion scores, suggesting that they might be less sensitive to immunotherapy. The roles of ABCB1, S100A9, NCL, PRDX6, YBX1, and POU2F1 in HCC have been reported. However, there have been no reports on the association between ALAD and HCC. Then we used bioinformatics to confirm that ALAD expression was lower in HCC and low expression of ALAD was an indicator of poor prognosis. Moreover, we found that ALAD expression was lower in HCC cells than that in normal human hepatocytes or tumor-adjacent tissues, it was negatively correlated with the pathological grade, and low expression of ALAD was related to poor prognosis in patients with HCC.

CONCLUSION

We have successfully established a novel prognostic signature based on moonlighting genes, with a strong predictive capability for prognosis, immune status, and possible response to immunotherapy. Additionally, we have identified ALAD as a prognostic biomarker for HCC.

摘要

背景

月亮基因可能参与肝细胞癌（HCC）的进展，基于月亮基因建立的预后特征可能有助于预测 HCC 患者的预后。

方法

本研究旨在构建基于 HCC 月亮基因的预后特征，并确定其与肿瘤微环境或免疫反应是否存在相关性。然后，我们使用 HCC 细胞系和 HCC cDNA 微阵列来阐明月亮基因在 HCC 预后中的作用。

结果

我们构建了一个基于 8 个月亮基因（ABCB1、S100A9、NCL、PRDX6、ALAD、YBX1、POU2F1、RPL5）的原始预后特征，具有很强的预后预测能力。该预后特征可能显示 HCC 患者的免疫状态，因为高危亚组的调节性 T 细胞、树突状细胞、滤泡辅助 T 细胞、巨噬细胞和主要组织相容性复合体-I 的评分显著更高，并且免疫检查点分子的表达水平不同。重要的是，高危亚组的患者表现出更高的肿瘤免疫功能障碍和排除评分，这表明他们可能对免疫治疗不太敏感。ABCB1、S100A9、NCL、PRDX6、YBX1 和 POU2F1 在 HCC 中的作用已被报道。然而，目前还没有关于 ALAD 与 HCC 之间关联的报道。然后，我们使用生物信息学方法证实 ALAD 在 HCC 中的表达较低，ALAD 表达较低是预后不良的指标。此外，我们发现 HCC 细胞中 ALAD 的表达低于正常人类肝细胞或肿瘤相邻组织，它与病理分级呈负相关，ALAD 表达较低与 HCC 患者的预后不良有关。