Research Of Differential Expression Of Aurora A And ERK Pathway In Oral Leukoplakia Tissues And Their Malignant Transformation Tissues

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, and ranks the sixth in all malignant tumors. OSCC has a higher incidence, which has an increasing trend in recent years in the East Asian countries and regions. The recurrence of OSCC is easy; the recurrence rate was 20%～48%. The five- year survival rate of OSCC has been less than 50% in the past 30 years, and some patients with lower age, there is a younger trend. OSCC is developed from oral precancerous lesions or premalignant state. Research results show that 17%-35% of OSCC patients are originated from oral leukoplakia. Oral leukoplakia (OLK) is white lesion of the oral mucosa that can not be characterized as any other definable lesion with clinical and histopathological diagnosis methods. OLK is the most commonly diagnosed premalignant lesion in the oral diseases and it is also most associated with the development of OSCC. According to WHO published data, OLK canceration rate is about 3%-5%.A study shows that non homogeneous leukoplakia canceration rate is about 13%-17.5%, even in some areas the rate can reach as high as 50%-70%. However, the mechanism of malignant transformation from OLK to OSCC is not completely understood. Therefore, researching molecular mechanism of canceration and exploring effective molecular markers for malignancy has important scientific significance and clinical application values for early detection, early diagnosis and early treatment, effectively improving the prognosis of the patients and preventing oral squamous cell carcinoma.Objective:In this study, we attempt to evaluate expression of Aurora A and important signal molecules in the Ras/Raf/MEK/ERK pathway in OLK tissues and OSCC tissues transformed from OLK, find effective molecular markers for predicting malignant transformation of OLK, and provide clues to find early treatment targets of malignant transformation of OLKMethods:Immunohistochemical technology was used to detect Aurora A, pRaf-1(S259), ERK1/2 and pERK1/2(T202/Y204) protein expression in 25 tissue samples of OLK and 21 OSCC clinical tumor specimens transformed from OLK. We also compared and analyzed differences in expression levels of these proteins between OLK tissues and OSCC tissues transformed from OLK.Result:The Aurora A positive staining was mainly expressed in the cytoplasm. According to the number of positive cells, Aurora A expression was observed in 8 of 25 OLK cases(32%) and in 15 of 21 OSCC cases(71%), there was a significant difference for the positive expression of Aurora A between OLK samples and tumor samples of OSCC (P=0.008, P<0.05).pRaf-1 (S259) positive staining was mainly located in the cytoplasm.According to the number of positive cells, pRaf-1 (S259) expression was observed in 16 of 25 OLK cases(64%) and in 12 of 21 OSCC cases(57%), there was no significant difference for the positive expression of pRaf-1 (S259) between OLK group and OSCC group (P=0.635,P>0.05).ERK1/2 positive staining was mainly expressed in the cytoplasm, According to the number of positive cells, ERK1/2 expression was observed in 17 of 25 OLK cases (68%) and in 17 of 21 OSCC cases (81%), there was no significant difference for the positive expression of ERK1/2 between OLK group and OSCC group (P=0.319, P> 0.05).pERK1/2 (T202/Y204) positive staining was mainly located in nucleus. According to the number of positive cells, pERKl/2 (T202/Y204) expression was observed in 6 of 25 OLK cases (24%)and in 17 of 21 OSCC cases (81%), there was a significant difference for the positive expression of pERK1/2 (T202/Y204) between OLK samples and OSCC samples(P<0.001).Upon analyzing the levels of Aurora A and pERK1/2(T202/Y204), a remarkable increase was observed in OSCC tissues transformed from OLK compared to OLK tissues. No statistically significant difference was found for pRaf-1 (S259) and ERK1/2 between OSCC tissues transformed from OLK and OLK tissues.Conclusion:Aurora A and the ERK pathway regulated by Aurora A, may be actively involved in the malignant transformation of OLK; Both high expression of Aurora A and high expression of more than 50% of positive cell rate of pERK1/2(T202/Y204) have suggestive significance for predicting malignant transformation of OLK; This study furtherly provides important research foundation and scientific basis for exploring the molecular mechanism and key treatment targets of OLK malignant transformation.