The DEAD-box RNA helicase, DDX60, Suppresses immunotherapy and promotes malignant progression of pancreatic cancer

Tiantian Lai; Xiaowen Su; Enhong Chen; Yue Tao; Shuo Zhang; Leisheng Wang; Yong Mao; Hao Hu

doi:10.1016/j.bbrep.2023.101488

The DEAD-box RNA helicase, DDX60, Suppresses immunotherapy and promotes malignant progression of pancreatic cancer

Biochem Biophys Rep. 2023 May 26:34:101488. doi: 10.1016/j.bbrep.2023.101488. eCollection 2023 Jul.

Authors

Tiantian Lai^{1

2}, Xiaowen Su^{1

2}, Enhong Chen¹, Yue Tao^{1

2}, Shuo Zhang^{1

2}, Leisheng Wang^{1

2}, Yong Mao³, Hao Hu^{1

2

4

5

6}

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
² Wuxi Medical College, Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
³ Medical oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
⁴ Hepatobiliary and Pancreatic Surgery, the Third Hospital Affiliated to Nantong University, Wuxi, 214041, China.
⁵ Medical School, Nantong University, Nantong, 226001, China.
⁶ Wuxi Institute of Hepatobiliary Surgery, Wuxi, 214122, China.

Abstract

Excessive proliferation, invasion, metastasis, and immune resistance in pancreatic cancer (PC) makes it one of the most lethal malignant tumors. Recently, DDX60 was found to be involved in the development of various tumors and in immunotherapy. Therefore, we aimed to investigate whether DDX60 is a new factor involved in PC immunotherapy. The DDX60 mRNA was screened using transcriptome sequencing (RNA-seq). The Cox and survival analysis of DDX60 was performed using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, clinical and immune infiltration data in the databases were analyzed and plotted using the R language. Clinical samples and in vitro experiments were used to determine the molecular evolution of DDX60 during PC progression. We found that DDX60 was upregulated in PC tissues (P value = 0.0083) and was associated with poor prognosis and short survival time of patients with PC. Results of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set variation analyses showed that viral defense, tumor, and immune-related pathways were significantly enriched in samples with high DDX60 expression. The Pearson correlation test demonstrated that DDX60 expression correlated strongly with immune checkpoint and immune system-related metagene clusters. Our results indicated that DDX60 promoted cell proliferation, migration, and invasion and was related to poor prognosis and immune resistance. Therefore, DDX60 may be a promising novel target for PC immunotherapy.

Keywords: DDX60; Immunotherapy; Pancreatic cancer; Prognosis; immune response.