High HDAC5 expression correlates with a poor prognosis and the tumor immune microenvironment in gastric cancer

Li Yuan; Can Hu; Pengcheng Yu; Zhehan Bao; Yuhang Xia; Bo Zhang; Yi Wang

doi:10.21037/atm-22-4325

High HDAC5 expression correlates with a poor prognosis and the tumor immune microenvironment in gastric cancer

Ann Transl Med. 2022 Sep;10(18):990. doi: 10.21037/atm-22-4325.

Authors

Li Yuan^#^{1

2

3}, Can Hu^#⁴, Pengcheng Yu⁴, Zhehan Bao⁴, Yuhang Xia⁴, Bo Zhang¹, Yi Wang⁴

Affiliations

¹ Department of Integrated Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
² Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
³ Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
⁴ First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.

^# Contributed equally.

Abstract

Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide and has a poor prognosis. Previous studies have confirmed differential histone deacetylase 5 (HDAC5) expression in various common tumors. HDAC5 is also associated with prognosis and plays a role in cancer cell proliferation, invasion, and metastasis, as well as the tumor immune microenvironment (TIME). However, HDAC5 in GC is not well understood. The aims of study were to investigate the HDAC5 expression correlates with prognosis and the TIME in GC.

Methods: A total of 355 tumor tissues and 300 matched paracancerous tissues were collected from GC patients who underwent radical surgery. The correlation between clinicopathological characteristics, immune-related factors and HDAC5 expression were analyzed. Univariate and multivariate Cox regression analyses were used to confirm the independent factors affecting the prognosis of GC. Survival curves were plotted using the Kaplan-Meier method. Furthermore, the stomach adenocarcinoma (STAD) dataset was downloaded from The Cancer Genome Atlas (TCGA). The expression levels of HDAC5 were defined as high or low using the gene set variance analysis (GSVA) package. Identification of differential immune infiltrating cells was performed by single sample gene set enrichment analysis (ssGSEA).

Results: The positive expression rate of HDAC5 was higher in tumor tissues than in paracancerous tissues (38.87% vs. 14.67%, P<0.001). Univariate and multivariate Cox analyses showed that HDAC5 was an independent factor affecting the prognosis of GC. The HDAC5 expression levels were correlated with age (P=0.046), smoking history (P=0.001), Lauren type (P=0.042), and pM stage (P=0.012). Furthermore, these levels were correlated with CD3⁺ T cells (P<0.001), CD4⁺ T cells (P<0.001), CD8⁺ T cells (P<0.001) and PD-L1 (P=0.001). Further analysis of patients in TCGA cohort confirmed the association between HDAC5 and activated CD4 T cells, activated CD8 T cells, and other immune infiltrating cells.

Conclusions: HDAC5 is highly expressed in tumor tissues and is an independent factor affecting the prognosis of GC. Additionally, HDAC5 can regulate the TIME of GC and is a potential target for immunotherapy.

Keywords: Gastric cancer (GC); histone deacetylase 5 (HDAC5); prognosis; tumor immune microenvironment (TIME); tumor-infiltrating lymphocytes (TILs).