Expression And Clinical Significance Of LBK1 Protein In Human Nasopharyngeal Carcinoma

Objective:Multidrug resistance has a strong impact on the prognosis of patient with NPC(nasalpharyngeal carcinoma).Seeking for the target of NPC chemotherapy is probably the breakthrough in improving the efficacy.Over the recent years,relevant reports found that LKB1(liver kinase B1),featured by antitumor effect,participates in cell adhesion,motion and signal transduction and adjusts the growth process of various tumor cells.Its inactivation is closely related to lung cancer,thyroid cancer,colon cancer,bile duct cancer,etc.LKB1 activates AMPK(Adenosine5‘-monophosphate AMP-activated protein kinase),its downstream target protein,through phosphorylation,and adjust mTOR(mammalian target of rapamycin)activity to jointly adjust the cell biological behavior for the antitumor effect.The deficiency of AMPK gene could accelerate the tumor induced by cancer gene.Insufficient AMPK activity is usually considered as one of the reasons triggering the development of malignant tumor,and the activation of AMPK could enhance the sensibility of chemotherapy drugs.At present,little research has been done on the relationship between LKB1 gene expression and NPC.The expression of LKB1 protein in NPC tissues is unclear,and the relationship between LKB1 protein expression and clinical and pathological characteristics of NPC is not clear.This studies aims to provide a new target for the NPC MDR research by collecting NPC tissue,studying the expression of LKB1 in NPC tissue,investigating the relations between its expression quantity and clinical pathology,as well as the chemotherapy sensitivity and prognosis.Methods:74 cases of NPC tissue samples and patients with complete clinical data were retrospectively selected.These patients were enrolled in the Department of Otorhinolaryngology Head and Neck Surgery,Affiliated Hospital of Southwest Medical University from March 2014 to August 2016.IHC EnVision two-step method was adopted to carry out IHC analysis on the specimens.After collection the images,Image-Pro Plus 6.0 analysis system was applied to detect the average MOD=SumIOD/SumArea of each image and analyze the characteristics of LKB1 expression in NPC;combined with the patient's follow-up data,the relationship between LKB1 expression and clinical pathology and prognosis was analyzed.ATP-TCP method vitro detection was adopted to detect the sensibility of NPC patient's tumor cell on 8 types of common chemotherapy drugs,and analyze the relations between LKB1expression and NPC chemosensitivity.Results:(1)LKB1 protein was expressed in brown in the cell nucleus and cell plasma of NPC tissues.The MOD value of LKB1 high expression and low expression group after staining was 0.165±0.017 and 0.122±0.019 respectively.The difference was of statistical significance(X~2=10.180,P=0.000);(2)For the comparison of patient's gender composition of the LKB1 high and low expression group,the difference was of statistical significance(X~2=6.469,P=0.011);for the comparison of composition of patient's age(X~2=0.054,P=0.816),histopathological type(X~2=2.882,P=0.216),T-staging(X~2=2.396,P=0.505),N staging(X~2=3.580,P=0.309),M staging(X~2=0.000,P=1.000)and clinical staging(X~2=6.468,P=0.078),the difference was of no statistical significance;(3)The patient's tumor progression rate of the LKB1 high expression group was 40.54%,and the LKB1 low expression group was45.95%.The difference of the two groups was of no statistical significance(X~2=0.220,P=0.639).The mortality of patient of LKB1 low expression group(40.54%)was higher than that of the high expression group(18.92%),and the difference was of statistical significance(X~2=4.140,P=0.042).For the comparison of overall survival of patients of LKB1 low expression group(59.46%)and high expression group(81.08%),the difference was of statistical significance(X~2=5.385,P=0.020).For the comparison of progression-free survival of patients of LKB1 low expression group(59.50%)and high expression group(54.10%),the difference of no statistical significance(X~2=1.644,P=0.200);(4)The drug resistance rate(35.14%)of NPC tissues to cyclophosphamide in LKB1 low expression group was higher than that of the high expression group(10.81%).The difference was of statistical significance(X~2=6.186,P=0.013).Conclusions:(1)LKB1 has different degrees of expression in NPC tissues;(2)The expression level of LKB1 in NPC tissues is in correlation with the patient's gender,but is not marked correlation with the age,patient type,TNM staging,and clinical staging;(3)The LKB1 expression level of NPC tissues is correlated to NPC patient's overall survival and mortality,but is not related to the tumor progression and progression-free survival rate;(4)The low expression of LKB1 protein in NPC tissues is correlated to the drug resistance of cyclophosphamide;(5)LKB1 expression in NPC tissues is expected to provide a new target and direction for the research of NPC prognosis monitoring and reversal of chemotherapy resistance.