Yao Senbang, Yin Xiangxiang, Chen Tingting, Chen Wenjun, Zuo He, Bi Ziran, Zhang Xiuqing, Jing Yanyan, Pang Lulian, Cheng Huaidong
Department of Oncology, The Second Affiliated Hospital of Anhui Medical University Hefei 230601, Anhui, China.
Department of Oncology, Anhui Medical University Hefei 230032, Anhui, China.
Am J Cancer Res. 2021 Nov 15;11(11):5319-5337. eCollection 2021.
Hepatocellular carcinoma is a malignant type of carcinoma with complicated pathogenesis. For HCC patients, there is not only a lack of valuable therapeutic targets, but also a lack of prognostic biomarker. The protein encoded by Aldehyde Dehydrogenase 2 Family Member (ALDH2) is a critical member of the aldehyde dehydrogenase family. Many researchers have found that ALDH2 mutations play an important role in the activation of hepatocellular carcinoma carcinogenic pathways. However, the clinicopathological meaning of ALDH2 in HCC and its relation with immune infiltration is still indistinguishable. In this study, we explored the expression of ALDH2 in 41 HCC tissues by immunohistochemistry. The clinicopathological meaning and molecular function of ALDH2 were analyzed and evaluated through comprehensive bioinformatics. ALDH2 expression in HCC was validated in TCGA, GEO and Oncomine databases, and a survival of ALDH2 based on TCGA database was analysed. LinkedOmics was used to classify the co-expressed genes of ALDH2 and its regulatory factors. The relation between ALDH2 and immune infiltration in HCC was further explored by TIMER. IHC results showed decreased levels of ALDH2 in HCC tumor tissues compared with corresponding normal liver tissues. The pathological grade and prognosis of patients with low expression of the ALDH2 gene were worse. Bioinformatics analysis results showed that ALDH2 was considerably down-regulated in cancer tissues compared with corresponding normal liver tissues in 8 GEO series and TCGA profile (all <0.05). A nomogram was designed using expression of ALDH2 and clinical factors. ALDH2 was correlated with dendritic cells and macrophages in immune infiltration. In conclusion, ALDH2 has significant prognostic value in hepatocellular carcinoma and they may play key roles in regulating tumor progression and the immune cells infiltration. Our results suggest that ALDH2 may be a new type of tumor biomarker, which can be used to judge the prognosis, targeted therapy and immunotherapy of patients with HCC.
肝细胞癌是一种发病机制复杂的恶性肿瘤。对于肝癌患者而言，不仅缺乏有价值的治疗靶点，而且缺乏预后生物标志物。醛脱氢酶2家族成员（ALDH2）编码的蛋白质是醛脱氢酶家族的关键成员。许多研究人员发现，ALDH2突变在肝细胞癌致癌途径的激活中起重要作用。然而，ALDH2在肝癌中的临床病理意义及其与免疫浸润的关系仍不明确。在本研究中，我们通过免疫组织化学检测了41例肝癌组织中ALDH2的表达。通过综合生物信息学分析和评估ALDH2的临床病理意义和分子功能。在TCGA、GEO和Oncomine数据库中验证了肝癌中ALDH2的表达，并基于TCGA数据库分析了ALDH2的生存情况。使用LinkedOmics对ALDH2及其调控因子的共表达基因进行分类。通过TIMER进一步探讨ALDH2与肝癌免疫浸润的关系。免疫组化结果显示，与相应的正常肝组织相比，肝癌肿瘤组织中ALDH2水平降低。ALDH2基因低表达患者的病理分级和预后较差。生物信息学分析结果显示，在8个GEO系列和TCGA数据中，与相应正常肝组织相比，癌组织中ALDH2明显下调（均<0.05）。利用ALDH2的表达和临床因素设计了一个列线图。ALDH2与免疫浸润中的树突状细胞和巨噬细胞相关。总之，ALDH2在肝细胞癌中具有显著的预后价值，可能在调节肿瘤进展和免疫细胞浸润中起关键作用。我们的结果表明，ALDH2可能是一种新型的肿瘤生物标志物，可用于判断肝癌患者的预后、靶向治疗和免疫治疗。
