| Background and ObjectiveRenal cell carcinoma(RCC)is mainly derived from renal tubular epithelial cells.It is the most common malignant tumor in the kidney.In recent years,its morbidity and mortality worldwide have continued to increase,which seriously threatens human physical and mental health.The pathological types of renal cell carcinoma include clear cell renal cell carcinoma,papillary renal cell carcinoma and chromophobe cell carcinoma,among which clear cell renal cell carcinoma(ccRCC)is the most common pathological type.Early renal cell carcinoma lacks typical clinical manifestations,and a significant number of patients have reached the advanced stage of the disease by the time of initial diagnosis.For the localized renal cell carcinoma,surgical treatment is currently preferred.For the advanced renal cell carcinoma,due to many problems in clinical application of various treatment methods including chemotherapy,radiotherapy,molecular targeted therapy and immunotherapy,there is still a lack of safe and effective treatment methods.Therefore,it is increasingly urgent to explore new biomarkers and therapeutic targets for renal cell carcinoma.The occurrence of tumors is closely related to the aging of the body in the clinical practice.The mitochondrial ribosomal protein S5(MRPS5),a structural protein that makes up the 28S subunit of the mitochondrial ribosomal body,is a longevity-related protein that regulates the life span of C.elegans through mitochondrial energy metabolism disorders and also affects the growth of tumors.Further studies show that the longevity-related protein is abnormally expressed in multiple malignant tumor tissues such as hepatic carcinoma,papillary thyroid carcinoma,and bladder cancer,which is closely related to the occurrence and development of tumors.It is speculated that MRPS5 may be an important biological marker of tumor and a key molecule for regulation.The relation of MRPS5 with renal cell carcinoma has not yet been reported at home and abroad.Therefore,MRPS5 have important sense in cancer,specially,in renal cell carcinoma.In this study,by detecting the expression of MRPS5 in cc RCC and analyzing its relationship with the clinicopathological parameters and prognosis of patients,it can not only fill the gap in the research of MRPS5in the field of renal cell carcinoma to a certain extent,but also clarify whether it is expected to become a biomarker for predicting the prognosis of patients and a new target for tumor targeted therapy.Methods(1)From April to August 2018 in the First Affiliated Hospital of Army Medical University,8 pairs of samples were collected from fresh cancer tissues and adjacent normal tissues(>2cm away from the tumor edge)diagnosed as cc RCC by postoperative pathological examination.A total of 104 paraffin-embedded cancer tissue specimens diagnosed as cc RCC by postoperative pathological examination from January 2007 to October 2012 in the First Affiliated Hospital of Army Medical University were collected.The clinical records were compiled in detail,and all patients were followed up.(2)RT-PCR,immunohistochemistry and western blot were used to detect the relative expression of MRPS5 in 8 pairs of fresh cancer tissues and adjacent normal tissues.Immunohistochemistry was used to detect the expression level of MRPS5 in paraffin-embedded cancer tissues of 104 cases,and All cases was divided into highexpression group and low expression group.?6 was considered as relatively high expression,?4 as relatively low expression.(3)?~2 test analyzed the relationship between clinical pathological parameters and MRPS5 expression level.(4)The survival curve was plotted by Kaplan-Meier,and the relationship between MRPS5 expression level and patient survival was tested by Log-rank.Cox proportional risk regression model was used to analyze the independent factors influencing the prognosis of patients.Results(1)The results of RT-PCR,immunohistochemistry and western blot experiments showed that the expression level of MRPS5 in cancer tissues was obviously reduced compared with that in adjacent normal tissues.In the 104 cases of cancerous issues,there were 61.5%patients(64 cases)with MRPS5 high expression and 38.5%patients(40 cases)with low expression.(2)MRPS5 protein expression levels were significantly associated with T classification(P=0.024)and Necrosis(P=0.044).(3)Overall survival(OS)and disease free survival(DFS)of patients with low MRPS5expression level group were dramatically shorter than those of patients with high MRPS5expression level group.Univariate Cox regression analysis showed that OS and DFS were correlated with tumor size,T stage,N stage,TNM clinical stage,Fuhrman grade,tumor necrosis and MRPS5 expression level(P<0.05).Multivariate Cox regression analysis found that OS and DFS were correlated with N stage,Fuhrman grade and MRPS5 expression level in ccRCC patients(P<0.05).Conclusions(1)The expression of MRPS5 in cancer tissues of ccRCC patients was remarkably lower than that in adjacent normal tissues.The expression level of MRPS5 was significantly related to the patients'T stage and tumor necrosis,and the postoperative survival of patients in the low expression group was worse than that in the high expression group,which might play a role in suppressing the development of renal cell carcinoma.(2)Low expression of MRPS5 was an independent risk factor affecting the prognosis of patients,and it could be used as a biomarker to evaluate the postoperative survival of patients.In-depth exploration of its molecular mechanism is expected to provide a more sufficient theoretical basis for the development of new drugs. |
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