Role of hyaluronan mediated motility receptor gene in oral squamous cell carcinoma and clinical prognosis.

OBJECTIVES

To screen genes related to the prognosis of oral squamous cell carcinoma (OSCC), and to explore its role and mechanism in the occurrence and development of OSCC.

METHODS

The data and the biological information in 330 OSCC tumor samples with head and neck squamous cell carcinoma (HNSCC) (OSCC group) and 37 normal samples (normal sample group) were screened and included, which came from the cancer genome atlas (TCGA) database. The differentially expressed genes were screened out by biological information analysis between the 2 groups. Furthermore, according to the tumor T grade (T1+T2 group: 114 cases, T3+T4 group: 216 cases), metastasis (positive group: 163 cases, negative group: 167 cases) and pathological grade (G1+G2 group: 244 cases, G3 +G4 group: 86 cases), the samples were divided into different groups respectively, and the differential genes were obtained separately, then the intersections of the differential expressed genes related to the prognosis of OSCC were screened. The different gene with the largest different multiples [hyaluronan mediated motility receptor (HMMR)] was selected for the next step in order to explore the relationship between HMMR and clinical grading (Stage I+II group: 69 cases, Stage III +IV group: 261 cases), as well as the relationship between T grade, metastasis and pathological grade. According to the median value of HMMR expression, the samples were divided into a high expression group and a low expression group (high expression group: 165 cases, low expression group: 165 cases); Kaplan-Meier survival analysis was used to explore the relationship between HMMR expression and prognosis. Tumor tissue specimens and corresponding normal oral mucosal tissue specimens in 50 OSCC patients, who underwent surgery in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from January 2014 to January 2016, were collected. Real-time RT-PCR and Western blotting and immunohistochemistry were used to verify the bioinformatics analysis results. Kaplan-Meier survival analysis was used to examine the relationship between the positive and negative expression of HMMR immunohistochemical staining (positive group: 32 cases, negative group: 18 cases) and prognostic related factors, and Cox regression analysis model was used to explore the prognostic risk factors of OSCC. The cell proliferation experiment and the cell scratch experiment were used to evaluate the effect of down-regulation of HMMR on the proliferation and migration of OSCC cells.

RESULTS

HMMR was highly expressed in OSCC tissues. Compared with the low HMMR expression group, the prognostic related factors in the HMMR high expression group was significantly lower, with significant difference (all <0.05); the high expression of HMMR was significantly related with the T grade (RR=1.33, <0.05), lymphonodus metastasis (RR=1.74, <0.05), the clinical stage (RR=1.49, <0.05), and it was an independent prognostic risk factor for OSCC (RR=1.45, <0.05). Down-regulation of HMMR can inhibit the proliferation and migration of OSCC cells, with significant difference (<0.05 or <0.01).

CONCLUSIONS

HMMR, as a proto-oncogene of OSCC, can promote the occurrence and development of OSCC, and it may be used as a potential early diagnostic marker and a new target for therapy.