| Background: Lung cancer is a leading cause of cancer-related deaths worldwide with the highest incidence and mortality.According to WHO classification,lung cancer can be divided into small cell lung cancer and non-small cell lung cancer,of which lung adenocarcinoma and lung squamous cell carcinoma account for about 90% of non-small cell lung cancer.With the accelerated progress of China's industrial development and changes in lifestyle,the incidence and mortality rate of lung cancer is still increasing,which has caused a serious burden on people's health.The most effective treatment for patients at an early stage is surgical resection,but recurrence of postoperative is high.In addition,numbers of patients are diagnosed at an advanced stage and the overall survival rate is poor.Because of the poor survival of lung cancer patients in advanced stages,it is important to identify novel effective prognostic biomarkers and therapeutic strategies to improve the treatment of lung cancer.BUB1 is a serine/threonine kinase protein bound to the kinetochore with its N-terminus.It is essential for spindle assembly checkpoint(SAC)signalling and for correct chromosome alignment during mitosis.During chromosome segregation microtubules need to be aligned properly to the kinetochore pairs.The spindle checkpoint controls this process by cell cycle delay in metaphase.In healthy cells,incorrectly attached chromosomes lead to an inhibition of the anaphase promoting complex or cyclosome(APC/C)by formation of the mitotic checkpoint complex(MCC)and phosphorylation of CDC20,both inhibiting APC/C.The role of BUB1 as a prognostic marker depends on the origin of the cancer.In low grade breast cancer and endometrial cancer frequent BUB1 expression was seen in cancers with a favorable course,whereas in ovarian and invasive breast cancer,frequent expression of BUB1 was associated with a poor prognosis.But up to now,there are few reports about BUB1 protein and non-small cell lung cancerObjectives: To clarify the expression level of BUB1 protein in lung cancer tissues;To investigate the correlation between the high expression of BUB1 protein and the clinicopathological parameters and prognosis of lung cancer.To provide theoretical and experimental basis for early diagnosis and prognostic evaluation of non-small cell lung cancerMethods: Immunohistochemistry was used to detect the expression of BUB1 protein in 78 cases of non-small cell lung cancer and 78 cases of adjacent normal tissues.Chi-square test and Fisher exact test were used to analyze the correlation between the high expression of BUB1 protein and the clinicopathological characteristics of non-small cell lung cancer.The Human Protein Atlas database,GEPIA database and TCGA database were used to verify the clinical value of BUB1 in the prognosis evaluation of non-small cell lung cancer patients.Results:(1)BUB1 protein is highly expressed in non-small cell lung cancer tissues,and its positive expression rate(33.3%,26/78)and strong positive expression rate(17.9%,14/78)in non-small cell lung cancer tissues were significantly higher than those in adjacent normal tissues(P<0.01).(2)Pearson's ?2 test showed that the abnormal expression of BUB1 protein was positively correlated with the stage(P=0.024),differentiation(P=0.001),lymph node metastasis(P=0.001),but not with sex,age,pathological type and tumor size.(3)The Human Protein Atlas database and GEPIA database showed that the overall survival and disease-free survival of lung cancer patients with high BUB1 expression were significantly shorter than those with low BUB1 expression(P<0.05).Conclusions:(1)BUB1 protein is highly expressed in non-small cell lung cancer.(2)The high expression of BUB1 protein was positively correlated with the clinical stage,differentiation degree and lymph node metastasis of lung cancer.(3)BUB1expression is shown as a potential biomarker of clinical outcomes in patients with non-small cell lung cancer and should be evaluated in prospective trials. |
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