Abstract
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 P<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.