Subcellular Localization Of β-arrestinl And Its Prognostic Value In Lung Adenocarcinoma

Background and aim:β-arrestins, including β-arrestinl and β-arrestin2, were initially appreciated for their capacity to sterically hinder the G protein-coupled receptors(GPCR) and ultimately resulted in receptor desensitization and endocytosis. Recent evidence revealed that β-arrestins can also function as versatile protein scaffolding platforms within the cytosol to ensure relevant transmission of information in space and time and thus an appropriate cellular response, p-arrestins play important roles in cancer progression and subcellular localization of β-arrestinl has been receiving more and more attention Although both P-arrestinl and β-arrestin2 contain nuclear localization signals, only β-arrestin2 has a nuclear export signal. As a consequence, P-arrestinl is found in both the cytoplasm and nucleus, while β-arrestin 2 is generally localized to the cytoplasm. However, there are little reports exploring the expression level and prognostic value of β-arrestinl in lung adenocarcinoma. Our purpose is to investigate the subcellular localization of P-arrestin1 and its prognostic value in lung adenocarcinomaMethod:Specimens were obtained from 133 patients with lung adenocarcinoma who had undergone surgical resection of primary tumor between June 2008 and August 2009 in Department of Thoracic of Shandong Provincial Hospital Affiliated to Shandong University. Immunohistochemistry technique was applied to detect the expression of β-arrestinl and p300 in 133 patients with lung adenocarcinoma. Kaplan-Meier method and Cox proportional hazards regression analyses were used to examine the relationship with survival.Results:Staining of the P-arrestinl protein was identified in the cytoplasm of cancer cells, p300, however, existed mostly in nucleus of tumor cells. The expression of β-arrestinl protein was investigated in 133 cases, of which 79(59%) showed high cytoplast immunoreactivity and 62(47%) showed high nuclear immunoreactivity. High expression of p300 was observed in 75 cases (56%) and low expression in 58 (44%). No significant association between β-arrestinl and clinicopathological variables was founded. The Kaplan-Meier plot showed patients with high expression of β-arrestinl, especially in nucleus, had a poorer overall survival (OS) and shorter disease-free survival (DFS) (p=0.028, p=0.015). Additionally, high p300 expression also resulted in a worse OS (p=0.039). For multivariable analyses, β-arrestinl expressed in nucleus was still an independent prognostic factor for DFS (p<0.01). The combination of nuclear β-arrestinl and p300 resulted in an independent prognostic factor with high discriminative power in outcomes concerning DFS (p=0.02)(for OS, β=0.052, a boundary significance).Conclusion:In conclusion, β-arrestinl in nucleus is associated with poor malignant tendency of lung adenocarcinoma patients and the predictive value of β-arrestinl in nucleus may be optimized by combining information about the expression of p300 acetyltransferase.