Expression Of Gut-enriched Kruppel-like Factor4in Gastric Cancer And Its Significance

Objective:Observer the expression of gut-enriched Kruppel-like factor4(KLF4) in gastric cancer and its association with clinicopathological parameters, and explore the effect of KLF4upon prognosis in gastric cancer and whether KLF4is a prognostic indicator for patients after radical surgery of gastric cancer.Methods:(1) KLF4mRNA level was detected in gastric cancer and adjacent normal mucosa by real-time polymerase chain reaction (PCR).(2) KLF4protein expression was measured by immunohistochemistry on tissue microarray, which containing primary gastric cancer, the corresponding para-cancerous tissue, and paired lymph node metastases (LNM).(3) Chi-square (x2) tests were used to analyze the association between KLF4protein expression and clinicopathological data. Univariate and multivariate Cox regression analyses was used to evaluated the effect of KLF4upon prognosis in gastric cancer.Results:(1) In these24paired samples,19(79.1%) analyzed samples expressed a lower level (at least a2-fold change) of KLF4mRNA in gastric cancer tissue specimens than in noncancerous tissue specimens, the difference is significant (P<0.01).(2) By immunohistochemistry, we observed that KLF4protein was localized in the nucleus and cytoplasm of gastric cancer cells and KLF4was down-regulated in gastric cancer compared with paired nomal gastric mucosa (43.18%vs79.16%), the difference is significant (P<0.01). Immnoreactivity of KLF4was significantly higher in LNM than in primary gastric cancer and normal mucosa, the difference is significant (P<0.01).(3) Association between KLF4protein expression and clinicopathologic factors in gastric cancer:The down-regulation of CDH17in gastric cancer was correlated withinvasion depth(P<0.05), clinical stage(P<0.05), LNM(P<0.05), distant metastasis(P<0.01). Following the developing of UICC stage, the expression of KLF4protein was declining subsequently. Among the samples with lymph node metastasis,77of148(52.03%) were positive compared with the samples without lymph node metastasis, of which71of116samples (47.97%) were positive, the difference is significant (P<0.01).(4) Association of KLF4protein expression with prognosis of patients with gastric cancer:overall survival of KLF4-negative patients was reduced compared with KLF4-positive patients [68.67%(103/150) VS86.84%(99/114); hazard ratio (HR)5.46;95%confidence interval (CI)3.2111.13; P<0.01];as well as the disease free survival(DFS) of gastric cancer patients [64.79%(92/142)VS84.82(94/112); HR4.2; CI2.108.46; P<0.01]; the Kaplan-Meier survival curve show that, the overall survival rate of KLF4-positive patients was significantly higher than the negative patients (P<0.05). Multivariate analysis showed that, the depth of invasion, UICC stage, distant metastasis, lymph node metastasis and KLF4prognostic factors affecting overall survival, depth of invasion, the UICC stage, distant metastasis, lymph node metastasis and KLF4is the prognosis of the tumor-free survival factorsConclusion:The down-regulation of KLF4in gastric cancer was correlated with clinical stage, invasion depth, LNM, distant metastasis, which showed that KLF4may participate in tumor invasion and metastasis and play an important role in gastric cancer progression. CDH17could serve as a biomarker to identify patients at risk of metastasis or recurrence after radical surgery, which have important research value for gastric cancer diagnosis, prognosis and treatment.