| Introduction: Gastric cancer(GC) is a common digestive tract cancer, ranking the second in all cancer-related morbidity and mortality in China. Accordingly, studying the mechanisms in the origin and development of gastric cancer, screening molecular biomarkers that can detects the disease in early stages and predicts the prognosis of cancer and that provides targeting point for the drug intervention, as well as preventing effectively the recurrence of gastric cancer have been some of the most urgent problems to be solved in this field. In the previous researches, a database containing more than 20 kinds of gastric cancer related proteins was established by screening experiments, which provided a clue for finding new tumor biomarkers. As one of main research objects, NUAK1 protein has been proved to play an important role in the pathogenesis of many kinds of solid tumors. NUAK1 is a protein involved in the regulation of energy and cell survival under harsh conditions. Recent studies have found that NUAK1 signaling pathway plays a role in promoting tumor cell growth, inhibiting apoptosis, and in the process of proliferation and glucose metabolism. At present, it has been confirmed that the m RNA and protein level of NUAK1 are increased in a variety of solid tumor tissues. But whether the NUAK1 expression in gastric cancer is related to carcinogenesis and development of gastric cancer, whether it can predict early recurrence and poor prognosis in patients with gastric cancer, and whether to provide more innovative treatment for gastric cancer, still belongs to the blank area.Objective: The purpose of the study is to detect the expression of NUAK1 protein in gastric cancer tissues, and analysis between NUAK1 protein and patients with clinical pathological parameters and prognosis, finally clarify the clinical significance of the expression of NUAK1 protein in gastric cancer.Methods: 117 patients were diagnosed as gastric cancer from December 2008 to April 2009 and had undergone partial or total gastrectomy at the Department of general surgery in The First Affiliated Hospital of Anhui Medical University were enrolled in this study. The expression patterns of the NUAK1 protein in 117 primary archival gastric cancer specimens and 46 adjacent normal epithelial tissues from patients were detected by immunohistochemistry assay. Staining evaluation results were analyzed statistically by SPSS software in relation to various clinicopathological characters, Recurrence-free Survival and Overall Survival.Results: Among the 117 patients analyzed using IHC, the mean score of NUAK1 in tumor tissues was 131.0 ± 4.80(mean ± s.e.) that was significantly greater than those(36.2 ± 2.80) observed in the matching adjacent mucosa(n=46)(p<0.05, Wilcoxon signed-rank test). In gastric cancer, NUAK1 protein expression level was significantly associated with histological differentiation(P=0.015), depth of invasion/T classification(P<0.05), lymph node metastasis(P<0.05), surgical resection(P=0.020) and pathological stage(P<0.05; Mann–Whitney U test). However, no correlations between NUAK1 expression and patients’ age, sex, tumor size, location, CA19-9 or CEA were detected. The Recurrence-free Survival and Overall Survival were significantly shorter for patients with NUAK1 higher scores than those with NUAK1 lower scores(Kaplan–Meier survival analysis). Multivariate analysis identified NUAK1 was an independent prognostic factor for both Recurrence-free Survival and Overall Survival(Cox regression analysis).Conclusion: Our findings provided convincing evidence for NUAK1 overexpression, which was tightly associated with more aggressive tumor behavior and a poor prognosis,indicating that NUAK1 is a valuable molecular biomarker for gastric cancer progression. It might also act as a promising target for both prognostic prediction and therapeutics. |
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