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. 2020 Mar 18;3(1):55-61.
doi: 10.1002/ame2.12105. eCollection 2020 Mar.

Clinical data analysis reveals the role of OGR1 (GPR68) in head and neck squamous cancer

Affiliations

Clinical data analysis reveals the role of OGR1 (GPR68) in head and neck squamous cancer

Wenlong Zhang et al. Animal Model Exp Med. .

Abstract

Background: Head and neck squamous cancer (HNSC) frequently occurs in the clinic. Revealing the role of the genes that correlate with cancer cell outgrowth will contribute to potential treatment target identification and tumor inhibition.

Methods: The gene expression profiles and gene ontology of the proton-sensing G-protein-coupled receptor OGR1 were analyzed using the TCGA (The Cancer Genome Atlas) database. The effects of sex, age, race, and degree of malignancy on HNSC were investigated, and the survival times of HNSC patients with high or low/medium expression levels of OGR1 were compared. Methylation of the OGR1 promoter CpG sites was also investigated and OGR1-related genes were analyzed using gene set enrichment analysis.

Results: OGR1 is overexpressed in HNSC patients. However, compared with the low/median expression group, the high OGR1 expression group did not have different survival rates. The OGR1 expression level differed across sex, age, race, and degree of malignancy, while the methylation of the OGR1 promoter CpG sites was maintained at a similar level. Gene set enrichment analysis revealed that OGR1 was positively correlated with head and neck cancer, cisplatin resistance, hypoxia, angiogenesis, cell migration, and TGF-β.

Conclusion: The expression of OGR1 correlated with HNSC progression and survival and thus can serve as a potential treatment target and prognostic marker.

Keywords: OGR1; TCGA; UALCAN; head and neck squamous cancer (HNSC).

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Figures

FIGURE 1
FIGURE 1
OGR1 is overexpressed in primary HNSC. Compared with the expression in normal tissues (n = 44), the expression of OGR1 in primary HNSC tissues (n = 520) is significantly higher (***P < .001)
FIGURE 2
FIGURE 2
OGR1 expression differs in different groups of HNSC patients. A, There were statistical differences in OGR1 expression between male and female HNSC patients (normal n = 44, male n = 383, female n = 136). B, The expression of OGR1 in HNSC patients of different ages was higher than that in the controls (normal: n = 44, 21‐40: n = 20, 41‐60: n = 236, 61‐80: n = 237, 81‐100: n = 24). C, OGR1 expression was higher in Caucasian (n = 444), African‐American (n = 47), and Asian (n = 11) patients than in the controls (n = 44). D, OGR1 expression was higher in grade 1 (n = 62), grade 2 (n = 303), and grade 3 (n = 125) disease than in the controls (n = 44), while grade 4 (n = 7) tissues had similar levels of OGR1 expression to the controls. (**P < .01, ***P < .001)
FIGURE 3
FIGURE 3
Comparison of the survival time between the high and low/medium OGR1 expression groups in HNSC patients. HNSC patients with high expression of OGR1 (n = 130) survived longer than low/medium OGR1 expression HNSC patients (n = 389)
FIGURE 4
FIGURE 4
OGR1 promoter CpG site methylation remains at a stable level across different groups of HNSC patients. A–E, The OGR1 promoter CpG sites methylation was maintained at a relatively stable level across different degrees of malignancy, race, sex, and age (the n is the same as that in each group in Figure 2) (*P < .05). F, OGR1 expression was negatively correlated with promoter CpG site methylation
FIGURE 5
FIGURE 5
Regression analysis of correlation between GPR 68 gene expression, methylation and patients’ age, malignancy and survival. A‐C, Correlation between gene expression of GPR68 and tumor malignancy, age, and patients’ overall survival. D‐F, Correlation between methylation of GPR68 and tumor malignancy, age, and patients’ overall survival
FIGURE 6
FIGURE 6
Molecular mechanisms underlie OGR1‐associated HNSC progression. A, The heat map shows 100 differentially expressed genes between the top and bottom 100 samples of HNSC ranked by OGR1 expression. B, OGR1 expression is positively correlated with HNSC, cisplatin resistance, hypoxia, angiogenesis, migration, and TGF‐β

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