| [Background]Gastric cancer,which remains almost the most frequent cancer,represents a major cause of cancer mortality because of its poor prognosis.In spite of dramatic improvements in early endoscopic diagnosis and multiple new type of treatments,patients at advanced stage often have poor prognosis because of metastatic diseases.Moreover,preoperative TNM stage and histological differentiation have low sensitivity for assessing prognosis.Thus,a better practical molecular prognostic markerl that assess progression of gastric cancer is urgently needed.Kruppel-like factors(KLFs)comprise a highly conserved family of zinc finger transcription factors,that are involved in a plethora of cellular processes,ranging from proliferation and apoptosis to differentiation,migration and pluripotency.KLF family members have been reported to be involved in the pathogenesis of many cancers,but little known about it with relationship with gastric cancer.[Purpose]The present study is to investigate the clinicopathological relationship of KLF7 in gastric cancer and explore the relation of KLF7 with gastric cancer patients’survival.[Methods]Part I:KLFs genes expression and clinical data of TCGA database are available from the website of Cancer Genomics Browser of University of California Santa Cruz(UCSC)(https://genome-cancer.ucsc.edu/).The database with fully characterized tumors and intact overall survival(OS)information,such as age,sex,age at initial diagnosis,and stage at diagnosis(tumor,node,metastasis,TNM classification).Variables were entered into univariate analysis and multivariate analysis,which were performed with Cox proportional hazard model,to get the prognostic factors for accessing the patient’s survival of gastric cancer.Part II:By training-validation approach,a total of 252 patients with gastric cancer who underwent gastrectomy were enrolled in this study to verify prognostic value of KLF7 expression for patient’s survival of gastric cancer.The expression of KLF7 was detected by immunohistochemical staining in specimens of gastric cancer and the adjacent normal gastric tissues.Meanwhile,Real-time PCR was also performed to examine the mRNA level of KLF7.Finally,the clinicopathological relationship with KLF7 expression in gastric cancer was analyzed.A univariate and multivariate Cox proportional hazards model was performed to verify the prognostic value of KLF7 expression for patient’s survival of gastric cancer.[Results]1.A total of 360 patients with gastric cancer from The Cancer Genome Atlas(TCGA)cohorts were collected in this study.Univariate and multivariate Cox proportional hazards model were used to assess the risk factors for survival.In the TCGA cohort,KLF7(HR:1.293,95%CI:1.002-1.672,p=0.049)was shown independently predictive of overall survival in gastric cancer after Cox proportional hazards analysis.2.In validated in-house cohort,according to the results of Immunohistochemic-al staining,comparing with adjacent normal tissues,KLF7 expression increased significantly in gastric cancer(p<0.001).And KLF7 staining was mainly detected in the cyteblast.Based on statistical analysis,KLF7 expression was positively correlated with the T stage(p=0.032),N stage(p=0.017).3.In validated in-house cohort,KLF7 were independent predictor for overall survival(KLF7 high,HR = 1.899,95%CI:1.218-2.959,p=0.005)and disease free survival(KLF7 high,HR = 1.669,95%CI:1.138-2.448,p=0.009).[Conclusion]Collectively,KLF family paly critical roles in gastric cancer,we found that KLF7 expression increased in gastric cancer tissues,which correlated with poor prognosis and metastasis.Meanwhile,KLF7 was identified as independent prognostic factor for survival outcome of gastric cancer.Further study is needed to understand more about KLFs family to gastric patients. |
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