Downregulation of zinc finger protein 71 expression in oral squamous cell carcinoma tissues and its underlying molecular mechanism

Fang-Cheng Jiang; Guo-Sheng Li; Jia-Yuan Luo; Zhi-Guang Huang; Yi-Wu Dang; Gang Chen; Juan He; Li Gao; Yu-Xing Tang; Gan-Guan Wei; Wen-Bin Dai; Zhen-Bo Feng

doi:10.1016/j.prp.2022.154109

Downregulation of zinc finger protein 71 expression in oral squamous cell carcinoma tissues and its underlying molecular mechanism

Pathol Res Pract. 2022 Oct:238:154109. doi: 10.1016/j.prp.2022.154109. Epub 2022 Sep 7.

Authors

Affiliations

¹ Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China; Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
² Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
³ Department of Otorhinolaryngology Head and Neck Surgery, 923 hospital of People's Liberation Army, 52 Zhiwu Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
⁴ Department of Pathology, Liuzhou People's Hospital, 8 Wenchang Road, Chengzhong District, Liuzhou, Guangxi Zhuang Autonomous Region 545006, PR China.
⁵ Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. Electronic address: fengzhenbo_gxmu@163.com.

PMID: 36115333
DOI: 10.1016/j.prp.2022.154109

Abstract

Background: Patients with oral squamous cell carcinoma (OSCC) have poor prognoses due to a limited understanding of the pathogenesis of OSCC. Zinc finger protein (ZNF) is the largest transcription factor family in the human genome and exert diverse and important functions. Nevertheless, the exact expression status and molecular mechanism of ZNF71 have not been described in OSCC. Therefore, this study aimed to identify the specific expression level of ZNF71 in OSCC tissues and to further interpret the potential molecular mechanism of ZNF71 in the pathogenesis of OSCC.

Methods: In-house immunohistochemical staining of 116 OSCC samples and 29 non-OSCC samples was employed to detect the expression status of ZNF71 at the protein level of OSCC tissues. Single-cell RNA sequencing data from 7 OSCC samples was used to explore the expression landscape of ZNF71 in different cell types from OSCC tissues. High-throughput RNA sequencing data and gene chips data from 893 OSCC samples and 301 non-OSCC samples were utilized to identify the specific expression level of ZNF71 at the bulk mRNA level of OSCC tissues. Here, standardized mean difference (SMD) value was applied to calculate the expression differences between OSCC group and non-OSCC group. Multiple datasets were included; hence, the results were considered to be more reliable. Sensitivity analysis was conducted to evaluate the stability of the results. Enrichment analysis and immune infiltration analysis were used to explore the underlying molecular mechanism of ZNF71 in OSCC.

Results: ZNF71 was significantly downregulated in OSCC tissues at the protein level (SMD = -1.96, 95 % confidence interval [95 % CI]: -2.43 to -1.50). ZNF71 was absent in various cell types from OSCC tissues including cancerous epithelial cells and tumor-infiltrating immune cells. ZNF71 was downregulated in OSCC tissues at the bulk mRNA level (SMD = -0.38, 95 % CI: -0.75 to -0.02). Enrichment analysis showed that positively and differentially co-expressed genes mainly concentrated on "herpes simplex virus 1 infection" and "regulation of plasma membrane bounded cell projection organization", and negatively and differentially co-expressed genes mainly participated in "cell cycle" and "DNA metabolic process". Moreover, the putative target genes of ZNF71 mainly participated in "cellular respiration" and "protein catabolic process". Finally, immune infiltration analysis revealed that ZNF71 expression was positively correlated with multiple immune cells including activated B cells, memory B cells, and natural killer (NK) cells, and negatively correlated with various immune cells, including CD56 bright NK cells, neutrophil, and immature dendritic cells.

Conclusion: The downregulation of ZNF71 may influence the initiation and promotion of OSCC by reducing immune infiltration, accelerating cell cycle progression, and affecting metabolic process, and this requires further research.

Keywords: Enrichment analysis; Immune infiltration; Immunohistochemistry (IHC) staining; Oral squamous cell carcinoma (OSCC); Single-cell RNA sequencing (scRNA-seq); Zinc finger protein 71 (ZNF71).