Clinical Analysis Of Risk Factors For Recurrence And Study Of Cancer Stem Cells In The Mechanism Of Radioresistance On Larvngeal Sauamous Cell Carcinoma

Background:Laryngeal squamous cell carcinoma(LSCC)is a common head and neck cancer.In the past decades,survival of LSCC has been declining due to preferred choice of non-surgical larynx-perversion therapy.Resistance of chemotherapy and radiotherapy also contributes to reduced survival and deteriorating prognosis.The mechanism of radioresistance is not yet defined.Cancer stem cell(CSC)hypothesis is one of the popular theories on the progression of cancer,which has been studied in several solid tumors such as glioma with promising results.Therapies targeting CSC emerged in recent years has been in experimental stage in some cancer types,while in LSCC the effect of similar therapies remain to be proved.Purpose:1.To define factors related to the recurrence of stage ? and stage ? laryngeal cancer,as a retrospective analysis of clinical records and follow-up study is conducted on patients.2.To determine the CSC related mechanism of laryngeal cancer radioresistance;to test a potential radioresistance modification therapy we newly proposed targeting CSC and GLUT1(glucose trasporter 1).Methods:1.A retrospective analysis of clinical records and follow-up study is conducted on patients who accepted therapy in the First Affiliated Hospital Zhejiang University.2.A CD133 positive Hep2 cell line is seperated;a radioresistent Hep2 cell line is acquired;difference of cell proliferation,apoptosis and GLUT1 expression is observed with or without GLUT1 inhibition using siRNA.Results:1.Relapse/metastasis is observed in 6 out of a total 41 patients,among which 3 suffered local recurrence,3 lung metastasis and 1 bone metastasis.One of the recurrent patients lose to follow-up.Relapse-free interval of the patients ranges from 5 to 17 months.For patients who died of LSCC relapse/metastasis,survival time ranges from 8 to 32 months.Univariate analysis indicates positive surgical margin is related to the recurrence of LSCC(OR=9.667,P=0.020<0.05).Multivariate analysis shows that positive surgical margin is an independent factor related to the recurrence of LSCC after radiotherapy.2.Transfection of siRNA-GLUT1 aiming inhibition of GLUT1 in CD133 positive Hep2 cell line shows reduced tumor cell proliferation,increased apoptosis and lower GLUT1 expression after radiation.Conclusion:1.Positive surgical margin is an independent factor of related to the recurrence of LSCC after radiotherapy.Therapy strategies should be carefully carried out in this situation.2.CD133 is an emerging CSC marker in LSCC.Modification of CD133 and GLUT could be a new target of LSCC therapy.