| Objective:The incidence and mortality of lung cancer rank first in the global malignancy.In China,the incidence of lung cancer is also rising year by year,which brings huge burden to society and families.In terms of treatment,surgery,radiotherapy,and chemotherapy have made progress,but the long-term survival rate of lung cancer is still very low,and the recurrence rate after initial treatment is very high.Therefore,we need to further study the mechanisms of its occurrence and development and find out more effective means of prevention and control.In addition to Vitamin D(Vit D)is known to regulate calcium and phosphorus metabolism,the current study has confirmed the role of this hormone in the field of cancer,such as Vit D is associated with Vitamin D receptor(VDR)in target cells and participates in cell growth regulation,apoptosis and cell differentiation,and inhibits cancer cell invasion,angiogenesis and metastasis.Studies have shown that VDR has abnormal expression in many tumors including colon cancer,breast cancer,prostate cancer,pancreatic cancer,esophageal cancer,ovarian cancer,and lung cancer.Changes in the Wnt/β-catenin signaling pathway have also shown significant significance in colorectal cancer,lung cancer,liver cancer,gastric cancer,endometrial cancer,ovarian cancer,prostate cancer,thyroid cancer,and Wilms tumor.The antitumor effect of Vit D can be achieved by inhibiting the WNT/β-catenin signaling pathway and has been demonstrated in colorectal cancer.Lung adenocarcinoma,as the most common pathological type of lung cancer,has received extensive attention from both domestic and foreign scholars for its pathogenesis and treatment.There has been no correlation analysis betweenVDR and β-catenin,cyclin D1,C-myc protein in WNT/β-catenin signaling pathways in human lung adenocarcinoma.Therefore,the expression of VDR and β-catenin,Cyclin D1,C-myc in 44 cases of lung adenocarcinoma tissues and the control group were detected by immunohistochemistry to investigate their expression and clinicopathological significance in lung adenocarcinoma.Matrials and Methods:1.Immunohistochemical method was used to detect the expression of VDR in 44 cases of lung adenocarcinoma and 9 cases of atypical hyperplasia/carcinoma in situ and 24 cases of normal tissues.analysing the relationship between the expression level of VDR and the patient’s clinical pathological factors,such as gender and age,T stage,lymph node metastasis,M staging,pathological type,vascular invasion,Ki67 proliferation index and clinical stage;using Immunohistochemical method was used to detect 44 cases of lung adenocarcinoma tissue and 24 cases of normal lung tissues,analysing the relationship between the expression level of β-catenin 、 C-myc 、Cyclin D1 and the patient’s clinical pathological factors,such as gender and age,T stage,lymph node metastasis,M staging,vascular invasion,Ki67 proliferation index and clinical stage;Finally,analysing the relationship between VDR,lung adenocarcinoma,and WNT/β-catenin signaling pathways.2.Statistical analysis was performed using SPSS 21.0 software package.Chi-square test or exact probability method was used among the indices and clinicopathological factors.Spearman rank correlation analysis was used among the indicators.P<0.05 was considered statistically significant.Results:一.The immunohistochemical expression of VDR in 44 cases of lung adenocarcinoma,9 cases of atypical hyperplasia/carcinoma in situ,and 24 normal lungtissues were analyzed.1.The expression of alveolar epithelium in normal lung tissue was weakly positive in cytoplasm and nucleus.The weak positive expression rate was 62.5%(15/24)and the negative expression rate was 37.5%(9/24).The bronchial mucosa epithelium was strongly positive,And the expression site of atypical hyperplasia/carcinoma in situ was in cytoplasm,most of which are weakly positive.the weak positive expression rate was 77.78%(7/9),the moderate positive expression rate was11.11%(1/9),the negative expression rate was 11.11%(1/9).The site of expression of adenocarcinoma tissue is mainly in the cytoplasm,occasionally nucleus expression.The strong positive expression rate was 47.72%(21/44),the moderate positive expression rate was 38.64%(17/44),the weak positive expression rate was11.36%(5/44),the negative expression rate was 2.27%(1/44).The expression of VDR in lung adenocarcinoma,atypical hyperplasia/ carcinoma in situ,and normal lung tissue is significantly different(P<0.05).2.The expression of VDR in different pathological types of lung adenocarcinoma was different.the In acinus type,the strong positive expression rate was 25%(7/28)and the moderate positive expression rate was 60.7%(17/28).The weak positive expression rate was 14.3%(4/28),the negative expression rate was 0(0/28).In papillary type,the strong positive expression rate was 50%(5/10),and the moderate positive rate expression was 30%(3/10),the weak positive expression rate was 10%(1/10),the negative expression rate was 10%(1/10).In solid type,the strong positive expression rate was 63.16%(12/19).The median positive rate was 31.58%(6/19),the weak positive rate was 5.26%(1/19),and the negative rate was 0(0/19).In micropapillary types,the strongly positive rate was 100%(8/8).The expression of four different pathological types of VDR in lung adenocarcinoma tissues was significantly different(P<0.05).In addition,VDR is strongly positive in both intravascular tumor emboli and free cancer cell nests.3.The abnormal expression of VDR was associated with lymph node metastasis(P =0.003),vascular invasion(P =0.032)and clinical stage(P =0.001),but there was no relationship between VDR and gender(P =0.104),age(P =0.50),T stage(P =0.54),M stage(P = 0.447),Ki67(P = 0.198).二.The results of immunohistochemical expression of β-catenin in 44 cases of lung adenocarcinoma and 24 cases of normal lung tissues were analyzed:1.The abnormal expression rate of β-catenin in lung adenocarcinoma was 72.73%(32/44);the abnormal expression rate in normal lung tissue was 20.83%(5/24),there was a significant difference(χ2=14.8323,P =0.0001).2.There was no relationship between abnormal expression of β-catenin and gender(P =0.419),age(P =0.255),T stage(P =0.164),lymph node metastasis(P=0.983),M stage(P =0.107)vascular invasion(P =0.622),Ki67(P =0.301),clinical stage(P =0.392).三.The immunohistochemical expression of Cyclin D1 in 44 cases of lung adenocarcinoma and 24 cases of normal lung tissues was analyzed:1.The expression of Cyclin D1 in lung adenocarcinoma is located in the nucleus,in which the strong positive expression rate was 40.91%(18/44),the moderate positive expression rate was 25%(11/44),the weak positive expression rate was 27.27%(12/44),and the negative expression rate was 6.82%(3/44);the expression was negative in normal lung tissue;there was a significant difference(P <0.05).2.There was no relationship between abnormal expression of Cyclin D1 and gender(P=0.742),age(P=0.54),T stage(P=0.483),lymph node metastasis(P=0.197),M stage(P=0.658),Vascular invasion(P=0.153),Ki67(P=0.271),clinical stage(P=0.327).四.The immunohistochemical expression of C-myc in 44 cases of lung adenocarcinoma and 24 cases of normal lung tissue was analyzed:1.The expression of C-myc in lung adenocarcinoma is located in the nucleus and cytoplasm,in which strong positive expression rate was 6.82%(3/44),the moderate positive expression rate was 6.82%(3/44).The weak positive rate was 38.64%(17/44),and the negative rate was 47.73%(21/44);the expression was negative in normal lung tissue;there was a significant difference(P <0.05).2.There was no relationship between abnormal expression of C-myc and gender(P =0.058),age(P =0.085),T stage(P =0.34),lymph node metastasis(P =0.680),M stage(P =0.678)vascular invasion(P =0.212),Ki67(P =0.142),clinical stage(P=0.828).五 Correlation analysis of the expression of VDR,β-catenin,Cyclin D1 and C-myc in 44 cases of lung adenocarcinoma showed that there was no correlation among these indexes(P>0.05).Conclusion:1.The expression of VDR in normal alveolar epithelium 、atypical hyperplasia/carcinoma in situ and lung adenocarcinoma are gradually increased,suggesting that VDR may be related to the occurrence and development of lung adenocarcinoma.The differential expression of VDR in different types of lung adenocarcinoma is enhanced with the increase of invasive,suggesting that VDR is related to the invasion and progression of lung adenocarcinoma.VDR is associated with lymph node metastasis,vascular invasion,and clinical stage in patients with lung adenocarcinoma,suggesting that VDR is associated with metastasis and prognosis of lung adenocarcinoma and may be a new therapeutic target.2.Abnormal expression of β-catenin,Cyclin D1 、 C-myc protein in lung adenocarcinoma tissue was significantly increased,but they are not related to the clinicopathological factors of patients with lung adenocarcinoma,suggesting that they are involved in the occurrence of lung adenocarcinoma,but may not be related to the tumor progression.3.The abnormal expression of VDR is not related to the expression of β-catenin and Cyclin D1 and C-myc,suggesting that may play an anti-tumor role by regulating some signaling pathway other than wnt/β-catenin. |
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