| BackgroundIn 2020,there are about 2.2 million new cases of lung cancer in the world,and the number of deaths is about 1.8 million.Lung cancer is the leading cause of death from malignant tumors.In recent years,due to the influence of various factors,the incidence of lung cancer in China is higher than before,and shows a younger trend.Non-small cell lung cancer(NSCLC)is the main type of lung cancer,accounting for about80%-85%.Most of the patients were in the middle and late stage when they were diagnosed,and the treatment effect was poor and the prognosis was poor,resulting in a low 5-year survival rate.Melanoma-associated antigen D4(MAGE-D4)is one of the melanoma-associated antigen(MAGE) family genes newly discovered in recent years.It is located on human chromosome XP11,full-length 7643bp,and consists of 13 exons.Related studies have shown that MAGE-D4 is highly expressed in gliomas,non-small cell lung cancer,esophageal squamous cell carcinoma and many other tumor tissues,but negative in surrounding normal tissues(except placenta and testis).The high expression of MAGE-D4 is related to the biological characteristics of tumor cell proliferation,migration and invasion.The patients with high expression of MAGE-D4 have poor prognosis.The Notch signal pathway consists of four receptors(Notch1,Notch2,Notch3,Notch4)and five ligands(Delta-like 1,3,4,Jagged1 and Jagged2).Among them,Notch3 is located on the chromosome19p13.12,which is encoded by 33 exons and is a single transmembrane heterodimer receptor protein composed of 2321 amino acids.Related studies have shown that Notch3 plays a role in promoting cancer in NSCLC,and its high expression is associated with poor prognosis.The overexpression of Ki67 in cancer cells significantly increases the ability of proliferation,invasion and migration,making it an appropriate biomarker for cancer progression,which has important prognostic and therapeutic significance.At present,there is no related research on the correlation of MAGE-D4,Notch3 and Ki67 and the role of their combination in NSCLC,so this study uses a retrospective method to study the expression of the three in non-small cell lung cancer.ObjectiveThe purpose of this study was to study the expression of MAGE-D4,Notch3 and Ki67 in tumor tissues of non-small cell lung cancer(NSCLC)and adjacent normal tissues,and to explore the relationship between MAGE-D4,Notch3,Ki67 and clinicopathological features and prognosis of patients with non-small cell lung cancer(NSCLC).MethodThe specimens were collected from Huaihe Hospital of Henan University from January 2017 to December 2020 and confirmed by the section reviewed by two deputy chief pathologists of the Department of Pathology.There were 232cases of tumor tissue and 100 cases of normal tissue adjacent to cancer(>3 cm away from tumor tissues),and tissue microarray was made.Immunohistochemical method was used for comparative analysis,and immunofluorescence method was used to observe the localization of MAGE-D4and Notch3 in cells.The purpose of this study was to observe the expression of MAGE-D4,Notch3 and Ki67in NSCLC tumor tissues and adjacent normal tissues,and to analyze their relationship with clinicopathological features and prognosis,in order to explore the clinical value of MAGE-D4,Notch3 and Ki67 in the diagnosis,treatment and prognosis of non-small cell lung cancer(NSCLC).Results1.The high expression rates of MAGE-D4,Notch3 and Ki67 were 73.71%,71.55%and 67.67% respectively in NSCLC,compared with normal tissues(MAGE-D4,Notch3 were 6%,7%,Ki67 was 0%respectively),the difference was statistically significant(x~2=128.702,116.681,128.384,P<0.001).2.The high expression of MAGE-D4 was correlated with the degree of differentiation and positive Ki67(x~2=9.498,4.010,P<0.05),but there was no significant difference between MAGE-D4 and sex,age,tumor size,histological type,TNM stage,capsule invasion,lymph node metastasis,family history,smoking history and tumor location(P>0.05).The high expression of Notch3 was correlated with tumor size,differentiation degree,TNM stage and Ki67 positive(x~2=4.414,4.776,7.102,7.266,P<0.05),but there was no significant difference with sex,age,histological type,capsule invasion,lymph node metastasis,family history,smoking history and tumor location(P>0.05).The positive expression of Ki67 was correlated with sex,tumor size,histological type,differentiation degree,TNM stage,lymph node metastasis,family history,smoking history and tumor location(x~2=26.860,9.447,34.204,7.321,10.341,16.485,4.496,21.418,7.223,P<0.05),but there was no significant difference with age and capsule invasion(P>0.05).3.In NSCLC tumor tissues,the expressions of MAGE-D4,Notch3 and Ki67 were positively correlated with each other(r_s=0.568,0.136,0.150,P<0.05).4.The expression of MAGE-D4,Notch3 and Ki67 was analyzed by Kaplan-Meier survival analysis.The survival time of the high expression group of MAGE-D4 and Notch3 was shorter than that of the low expression group,and the survival time of the positive expression group of Ki67 was shorter than that of the negative expression group.The difference was statistically significant(x~2=6.052,4.022,4.362,P<0.05).5.Kaplan-Meier survival analysis showed that the survival time of patients with NSCLC was related to the degree of differentiation,and the difference was statistically significant(x~2=5.143,P<0.05).6.The results of immunohistochemistry and immunofluorescence showed that the localization of MAGE-D4 and Notch3 in cells was the same in the two staining methods.Conclusions1.The expression of MAGE-D4,Notch3 and Ki67 is closely related to the occurrence,development and prognosis of non-small cell lung cancer.2.The high expression of MAGE-D4 and Notch3 and the positive expression of Ki67 indicate that the prognosis of NSCLC is poor and the overall survival time is shortened.3.MAGE-D4,Notch3 and Ki67 were positively correlated with each other. |
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