Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors

Donghui Liu; Xuyao Wang; Enhong Shi; Liru Wang; Minghao Nie; Long Li; Qingxin Jiang; Pengyu Kong; Shuai Shi; Chao Wang; Sen Yan; Zhihui Qin; Shuang Zhao

doi:10.3389/fgene.2021.699910

Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors

Front Genet. 2021 Jul 16:12:699910. doi: 10.3389/fgene.2021.699910. eCollection 2021.

Authors

Donghui Liu¹, Xuyao Wang², Enhong Shi¹, Liru Wang¹, Minghao Nie³, Long Li⁴, Qingxin Jiang⁵, Pengyu Kong⁶, Shuai Shi⁷, Chao Wang⁸, Sen Yan⁹, Zhihui Qin¹⁰, Shuang Zhao¹

Affiliations

¹ Department of Oncology, Heilongjiang Provincial Hospital, Harbin, China.
² Department of Pharmacy, Harbin Second Hospital, Harbin, China.
³ Department of Pathology, Heilongjiang Provincial Hospital, Harbin, China.
⁴ Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁵ Department of General Surgery, Harbin 242 Hospital of AVIC, Harbin, China.
⁶ Department of Orthopedics, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁷ Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
⁸ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
⁹ Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁰ Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: The SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.

Methods: The Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).

Results: In ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.

Conclusion: SMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

Keywords: SMYD; TP53; clinical stage; gene mutation; immune infiltration; malignant tumors; prognosis.