The clinical significance of interleukin 24 and its potential molecular mechanism in laryngeal squamous cell carcinoma

Article type: Research Article

Authors: Tang, Xiao-Zhun^{a; 1} | Zhou, Xian-Guo^{b; 1} | Zhang, Xiao-Guohui^c | Li, Guo-Sheng^c | Chen, Gang^c | Dang, Yi-Wu^c | Huang, Zhi-Guang^c | Li, Ming-Xuan^c | Liang, Yao^c | Yao, Yu-Xuan^c | Chen, Xiao-Yi^c | Rong, Min-Hua^b | Huang, Su-Ning^{d; *}

Affiliations: [a] Department of Head and Neck Tumor Surgery, Guangxi Medical University Cancer Hospital, Guangxi, China | [b] Department of Research, Guangxi Medical University Cancer Hospital, Guangxi, China | [c] Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Guangxi, China | [d] Department of Radiotherapy, Guangxi Medical University Cancer Hospital, Guangxi, China

Correspondence: [*] Corresponding authors: %Min-Hua␣Rong, %Department␣of␣Research,␣Guangxi␣Medical␣University␣Cancer␣Hospital,␣71␣Hedi␣Road,␣Nanning,␣Guangxi,␣China. %****␣cbm-29-cbm201441_temp.tex␣Line␣125␣****Su-Ning Huang, Department of Radiotherapy, Guangxi Medical University Cancer Hospital, Guangxi, China. E-mail: [email protected].

Note: [1] Xiao-Zhun Tang and Xian-Guo Zhou are both co-first authors.

Abstract: Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86–0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.

Keywords: Interleukin 24, laryngeal squamous cell carcinoma, immunohistochemistry, RNA-sequencing, microarray

DOI: 10.3233/CBM-201441

Journal: Cancer Biomarkers, vol. 29, no. 1, pp. 111-124, 2020