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. 2017 Sep;14(3):3633-3640.
doi: 10.3892/ol.2017.6633. Epub 2017 Jul 20.

Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma

Daisuke Furukawa  1   2   3 , Tsuyoshi Chijiwa  4 , Masahiro Matsuyama  3 , Masaya Mukai  5 , Ei-Ichi Matsuo  6 , Osamu Nishimura  7 , Kenji Kawai  4 , Hiroshi Suemizu  4 , Toshio Nakagohri  3 , Soji Ozawa  3 , Kazuaki Shimada  8 , Nobuyoshi Hiraoka  1   2 , Masato Nakamura  9
Affiliations

Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma

Daisuke Furukawa et al. Oncol Lett. 2017 Sep.

Abstract

Pancreatic ductal carcinoma (PDC) is one of the major causes of cancer-associated mortality globally due to its high potential for distant metastasis. To understand hematogenous metastasis, the molecular expression profiles of weak metastatic PDC cell subline BxPC-3 and highly liver-metastatic cell subline LM-BxPC-3 were compared, and zinc finger protein 185 (ZNF185) was identified as a molecule that is upregulated in LM-BxPC-3 cells. The aim of the present study was to evaluate the clinicopathological significance of ZNF185 in PDC. Using immunohistochemistry, ZNF185 expression was investigated in 182 patients with PDC, in association with numerous clinicopathological variables. The expression profile of ZNF185 was also characterized using xenograft models. In contrast to parent BxPC-3 cells in subcutaneous transplanted tumor foci, which only expressed ZNF185 on their plasma membrane (m)ZNF185, LM-BxPC-3 cells in liver-metastatic foci that were formed subsequent to transplantation all expressed cytoplasmic (c)ZNF185. Additionally, 51% of the cells at the periphery of the tumor foci expressed mZNF185. Expression of cZNF185, and of mZNF185 and cZNF185 combined was identified in 93 and 39% of clinical patients with PDC, respectively. Patients with mZNF185-negative and -positive PDC exhibited a median survival time of 30.2 months and 21.3 months, respectively. Multivariate analysis indicated that the expression of mZNF185 is closely associated with a shorter overall survival time. Increased marked venous invasion was more prevalent in patients who were mZNF185-positive, as compared with patients who were mZNF185-negative. These data suggest that the expression of mZNF185 is an independent and unfavorable prognosticator in patients with PDC. The results suggested that the amount and subcellular location of ZNF185 are correlated with the position of the cancer cells expressing it within the nests. Additionally, the subcellular location of ZNF185 may be important to its biological function.

Keywords: hematogenous metastasis; pancreatic ductal carcinoma; prognosis; subcellular location; zinc finger protein 185.

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Figures

Figure 1.
Figure 1.
Immunohistochemical features of transplanted cancer cells. These representative images demonstrate: (A) ×50 and (B) ×200 magnification images of liver foci from the highly-metastatic LM-BxPC-3 cancer cell line; (C) ×50 and (D) ×200 magnification images of subcutaneous foci of the poorly-metastatic BxPC-3 cancer cell line. (E) A comparison of mZNF185-positive cancer cells. The percentage of mZNF185-immunopositive cells between subcutaneous tumor foci of the transplanted BxPC-3 cells and liver-metastatic tumor foci of the transplanted LM-BxPC-3 cells. These were also compared between the central and peripheral cells in the nests. The line in the middle of the boxes represents the median value. The bottom and top of the box indicate the 25 and 75th percentile, respectively. The T-bars indicate the 95% confidence interval. mZNF185, plasma membrane-associated zinc finger protein 185.
Figure 2.
Figure 2.
Immunohistochemical features of pancreatic ductal carcinoma. (A) Adenocarcinoma cells are immunopositive for ZNF185 in membranous and cytoplasmic patterns, particularly in the plasma membrane of cancer cells attached to the stroma. Non-cancerous ductular cells also express ZNF185 (top left). Magnification, ×50. (B) Adenocarcinoma cells strongly express ZNF185 in the plasma membrane and cytoplasm. Magnification, ×100. ZNF185, zinc finger protein 185.
Figure 3.
Figure 3.
Kaplan-Meier survival curves comparing the (A) overall survival and (B) disease-free survival between the groups, indicating the positive (dotted line) and negative (solid line) expression of mZNF185. *P<0.05 from the log-rank test. mZNF185, plasma membrane-associated zinc finger protein 185.
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References

    1. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. doi: 10.1056/NEJMra0901557. - DOI - PubMed
    1. Hruban RH, Boffetta P, Hiraoka N, Iacobuzio-Donahue C, Kato Y, Kern SE, Klimstra DS, Kloppel G, Maitra A, Offerhaus GJA, et al. Ductal Adenocarcinoma of the Pancreas. In: World Health Organization Classification of Tumours. Pathology & Genetics. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. Tumours of the Digestive System. IARC; Lyon: 2010. pp. 281–291.
    1. Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806–1813. doi: 10.1200/JCO.2008.17.7188. - DOI - PMC - PubMed
    1. Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013;31:1640–1648. doi: 10.1200/JCO.2012.43.3680. - DOI - PubMed
    1. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moor M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–1703. doi: 10.1056/NEJMoa1304369. - DOI - PMC - PubMed
-