Cervical Lymphatic Neck Metastasis Biomarker Screening And Clinicopathological Analysis Of Patients With Early-stage Tongue Carcinoma

OBJECTIVE To analyze the relevant clinicopathologic features of cervical lymph node metastasis in early tongue squamous cell carcinoma and to screen the biomarkers which can predict metastasis.MATERIALS AND METHODS Two hundred twenty-one cases of early tongue carcinoma of cT1-2N0M0 were randomly selected and the selective neck dissection group and neck observation group to analyze the relevant clinicopathological factors of cervical lymphatic metastasis from Novermber 2008 in April 2014.Twelve samples including tumor and normal specimens were screened to explore mRNA marker related to metastasis which were selected by table of random number using bioinformatics analysis,Special genes of higher level were validad by PCR and immunohistochemical detection;Tumor specimens were selected for whole exon sequencing,and the DNA level difference markers were screened.RESULTS Cervical lymphatic metastasis in patients with early tongue carcinoma was correlated with perineural invasion factor.(p=0.004).In 44 patients,the total exon sequencing was carried out: there was a statistical correlation between the somatic mutation NOTCH1(p=0.007)and MUC20(p=0.035)and cervical lymph node metastasis.The number of copies of 22 genes was mutated and Cervical lymphatic metastasis could be predicted by 22 genes copy number variance.The average area of the ROC curve of cervical lymph node metastasis was 0.855.One hundred and seven specific genes correlated to metastasis using transcriptome microarray,and MFAP5 and TNNC1 were significantly increased in mRNA expression and protein levels in patients with cervical lymphatic metastasis(MFAP5:p=0.0034;TNNC1:p=0.0142),and overall survival.By combined predictors MFAP5 and PNI could improve the predictive efficiency of cervical lymphatic metastasis.CONCLUSION Cervical lymph node metastasis was related to perineural invasion in pathological morphology level.NOTCH1 and MUC20 were identified somatic mutations in the cervical lymphatic metastasis of tongue cancer,and the change of gene copy number variance can indicate the risk of cervical lymph node metastasis.Positive expression of MFAP5 and TNNC1 may be suggestive of cervical lymph node metastasis and poor prognosis.The combined prediction of MFAP5 protein expression and PNI positive is of significance predicting for cervical lymph node metastasis in early tongue carcinoma.