Expression profile and prognostic value of SAV1 in patients with pancreatic ductal adenocarcinoma
SAV1 is a human homolog of salvador that contains two protein-protein interaction modules known as WW domains and acts as a scaffolding protein for Hpo and Warts. SAV1 is known to be a tumor suppressor, but its clinical and prognostic implications remain elusive. This study aimed at evaluating the prognostic significance and associated expression of SAV1 in pancreatic ductal adenocarcinoma (PDAC) patients. The expression of SAV1 in tissue specimens of PDAC patients were assayed with immunohistochemistry on a tissue microarray. The correlations between SAV1 expression and clinicopathological characteristics were analyzed by Pearson’s chi-square test, Fisher’s exact test, and Spearman’s rank. The prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. The percentage of SAV1 expression in PDAC (50.6 %) was significantly lower than those in paratumor tissues (69.9 %) (P = 0.017). Expression of SAV1 was only significantly correlated with histological differentiation (P = 0.025) and N classification (P = 0.009). On multivariate analysis, elevated expression of SAV1 and N0 was a significant favorable prognostic factor of OS. Our study demonstrated for the first time that lower expression of SAV1 might be involved in the progression of PDAC, suggesting that SAV1 may be a potential prognostic marker and target for PDAC therapy.
KeywordsSAV1 Pancreatic ductal adenocarcinoma Prognosis Immunohistochemistry
This work was supported by grant 81171887 and 91229117 from the National Natural Science Foundation of China (to L. Wang).
Compliance with ethical standards
The use of the tissue microarray was approved by the Medical ethics committee of the general hospital. And each patient included in the study has signed an informed consent form before the tissue was collected.
Conflicts of interest
- 4.Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16:836–47.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.ZP X, Zhu JS, Zhang Q, Wang XY. A breakdown of the hippo pathway in gastric cancer. Hepato-Gastroenterology. 2011;58:1611–7.Google Scholar
- 12.Matsuura K, Nakada C, Mashio M, Narimatsu T, Yoshimoto T, Tanigawa M, Tsukamoto Y, Hijiya N, Takeuchi I, Nomura T, Sato F, Mimata H, Seto M, Moriyama M. Downregulation of sav1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma. BMC Cancer. 2011;11:523.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Zhang W, Nandakumar N, Shi Y, Manzano M, Smith A, Graham G, Gupta S, Vietsch EE, Laughlin SZ, Wadhwa M, Chetram M, Joshi M, Wang F, Kallakury B, Toretsky J, Wellstein A, Yi C. Downstream of mutant kras, the transcription regulator yap is essential for neoplastic progression to pancreatic ductal adenocarcinoma. Sci Signal. 2014;7:ra42.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.MZ X, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT, Luk JM. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer-. Am Cancer Soc. 2009;115:4576–85.Google Scholar