Soluble a‑proliferation‑inducing ligand (sAPRIL), a novel serum biomarker predicting the recurrence and metastasis of pancreatic adenocarcinoma after surgery

Han,Lei; Zhang,Wei; Song,Fulin; Guo,Yang; Guo,Kejian; Zhou,Wenping

doi:10.3892/mmr.2014.2443

Soluble a‑proliferation‑inducing ligand (sAPRIL), a novel serum biomarker predicting the recurrence and metastasis of pancreatic adenocarcinoma after surgery

Authors:
- Lei Han
- Wei Zhang
- Fulin Song
- Yang Guo
- Kejian Guo
- Wenping Zhou
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Affiliations: Department of Hepatobiliary and Pancreas Surgery, The General Hospital of Shenyang Military Region, Shenyang, Liaoning 110016, P.R. China, Department of Pathology, The General Hospital of Shenyang Military Region, Shenyang, Liaoning 110016, P.R. China, Department of General Surgery, College of Clinical Medical Sciences, China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: August 4, 2014 https://doi.org/10.3892/mmr.2014.2443
Pages: 1978-1984

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Abstract

Pancreatic adenocarcinoma (PA) is a leading cause of adult cancer mortality, and surgery is still the best available treatment strategy. However, PA can recur at any time and has limited prognosis. It is therefore necessary to explore novel serum biomarkers of PA to allow the early diagnosis of PA. Soluble a‑proliferation‑inducing ligand (sAPRIL), a promising inducer of the epithelial‑mesenchymal transition (EMT), is often found overexpressed in a variety of autoimmune diseases. To determine whether serum sAPRIL can constitute a PA biomarker, the protein level of sAPRIL was examined by immunohistochemistry and western blot, and the mRNA level was quantified by RT‑qPCR. The PA cell line PanC‑1 was transfected with vectors bearing the sAPRIL gene and sAPRIL short hairpin RNA (shRNA) oligos. Increased expression of serum sAPRIL was observed in patients with PA recurrence or metastasis after five‑year surgery compared to subjects without PA recurrence or metastasis. The growth rate of PanC‑1 cells transfected with the sAPRIL expression vector was increased by 23% (P<0.01, vs. control group), and was reduced by 17% (P<0.01, vs. control group) in the sAPRIL shRNA‑silenced cell line. Thus, sAPRIL is highly expressed in PA, and serum levels of sAPRIL can serve as a useful indicator for the recurrence or metastasis of PA after surgery. Additional validation studies on the use of serum sAPRIL as a diagnostic marker in PA are however needed.

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1	Zhang R, Humphreys I, Sahu RP, Shi Y and Srivastava SK: In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis. 13:1465–1478. 2008. View Article : Google Scholar : PubMed/NCBI
2	Stathis A and Moore MJ: Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol. 7:163–172. 2010. View Article : Google Scholar : PubMed/NCBI
3	Aparicio JR, Martínez J, Niveiro M, et al: Direct intracystic biopsy and pancreatic cystoscopy through a 19-gauge needle EUS (with videos). Gastrointest Endosc. 72:1285–1288. 2010. View Article : Google Scholar : PubMed/NCBI
4	Falco A, Rosati A, Festa M, et al: BAG3 is a novel serum biomarker for pancreatic adenocarcinomas. Am J Gastroenterol. 108:1178–1180. 2013. View Article : Google Scholar : PubMed/NCBI
5	Kosanam H, Prassas I, Chrystoja CC, et al: Laminin, gamma 2 (LAMC2): a promising new putative pancreatic cancer biomarker identified by proteomic analysis of pancreatic adenocarcinoma tissues. Mol Cell Proteomics. 12:2820–2832. 2013. View Article : Google Scholar
6	Wang Y, Kuramitsu Y, Ueno T, et al: Proteomic differential display identifies upregulated vinculin as a possible biomarker of pancreatic cancer. Oncol Rep. 28:1845–1850. 2012.PubMed/NCBI
7	Wang T, Wentz SC, Ausborn NL, et al: Pattern of breast cancer susceptibility gene 1 expression is a potential prognostic biomarker in resectable pancreatic ductal adenocarcinoma. Pancreas. 42:977–982. 2013. View Article : Google Scholar : PubMed/NCBI
8	Tempero MA, Klimstra D, Berlin J, et al: Changing the way we do business: recommendations to accelerate biomarker development in pancreatic cancer. Clin Cancer Res. 19:538–540. 2013. View Article : Google Scholar
9	Ray P, Sullenger BA and White RR: Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications. Nucleic Acid Ther. 23:435–442. 2013. View Article : Google Scholar
10	Ray P, Rialon-Guevara KL, Veras E, Sullenger BA and White RR: Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker. J Clin Invest. 122:1734–1741. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ono M, Kamita M, Murakoshi Y, et al: Biomarker discovery of pancreatic and gastrointestinal cancer by 2DICAL: 2-dimensional image-converted analysis of liquid chromatography and mass spectrometry. Int J Proteomics. 2012:8974122012.PubMed/NCBI
12	Lyn-Cook BD, Yan-Sanders Y, Moore S, Taylor S, Word B and Hammons GJ: Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: A potential biomarker of early damage in the pancreas. Cell Biol Toxicol. 22:73–80. 2006. View Article : Google Scholar
13	Lau C, Kim Y, Chia D, et al: Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem. 288:26888–26897. 2013. View Article : Google Scholar : PubMed/NCBI
14	Hahne M, Kataoka T, Schröter M, et al: APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med. 188:1185–1190. 1998. View Article : Google Scholar : PubMed/NCBI
15	Chuang MJ, Sun KH, Tang SJ, Deng MW, Wu YH, Sung JS, Cha TL and Sun GH: Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells. Cancer Sci. 99:905–913. 2008. View Article : Google Scholar
16	Takahashi E, Nagano O, Ishimoto T, Yae T, Suzuki Y, Shinoda T, Nakamura S, Niwa S, Ikeda S and Koga H: Tumor necrosis factor-α regulates transforming growth factor-β-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction. J Biol Chem. 285:4060–4073. 2010.
17	Dillon SR, Harder B, Lewis KB, et al: B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin. Arthritis Res Ther. 12:R482010. View Article : Google Scholar
18	Xin G, Cui Z, Su Y, Xu LX, Zhao MH and Li KS: Serum BAFF and APRIL might be associated with disease activity and kidney damage in patients with anti-glomerular basement membrane disease. Nephrology (Carlton). 18:209–214. 2013. View Article : Google Scholar
19	Pollard RP, Abdulahad WH, Vissink A, et al: Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjogren’s syndrome: data from a placebo-controlled clinical trial. Ann Rheum Dis. 72:146–148. 2013.
20	Gheita TA, Raafat H, Khalil H and Hussein H: Serum level of APRIL/BLyS in Behcet’s disease patients: clinical significance in uveitis and disease activity. Mod Rheumatol. 23:542–546. 2013.PubMed/NCBI
21	Kiyama K, Kawabata D, Hosono Y, et al: Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance. Arthritis Res Ther. 14:R862012. View Article : Google Scholar : PubMed/NCBI
22	Wang F, Chen L, Ding W, et al: Serum APRIL, a potential tumor marker in pancreatic cancer. Clin Chem Lab Med. 49:1715–1719. 2011. View Article : Google Scholar : PubMed/NCBI
23	Tecchio C, Nichele I, Mosna F, et al: A proliferation-inducing ligand (APRIL) serum levels predict time to first treatment in patients affected by B-cell chronic lymphocytic leukemia. Eur J Haematol. 87:228–234. 2011. View Article : Google Scholar
24	Ding W, Wang J, Wang F, et al: Serum sAPRIL: a potential tumor-associated biomarker to colorectal cancer. Clin Biochem. 46:1590–1594. 2013. View Article : Google Scholar : PubMed/NCBI
25	Sobin LH, Gospodarowicz MK and Wittekind C: TNM Classification of Malignant Tumours. 28. 7th edition. Wiley-Blackwell; West Sussex, UK: pp. 231–234. 2009
26	Takano S, Yoshitomi H, Togawa A, et al: Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells. Oncogene. 27:2810–2822. 2008. View Article : Google Scholar : PubMed/NCBI
27	Blumenstein B, Saad F, Hotte S, et al: Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen. Cancer Med. 2:468–477. 2013. View Article : Google Scholar : PubMed/NCBI
28	Wu Y, Du X, Xue C, et al: Quantification of serum SOX2 DNA with FQ-PCR potentially provides a diagnostic biomarker for lung cancer. Med Oncol. 30:7372013. View Article : Google Scholar : PubMed/NCBI
29	Harima Y, Ikeda K, Utsunomiya K, et al: Apolipoprotein C-II is a potential serum biomarker as a prognostic factor of locally advanced cervical cancer after chemoradiation therapy. Int J Radiat Oncol Biol Phys. 87:1155–1161. 2013. View Article : Google Scholar
30	Toiyama Y, Hur K, Tanaka K, et al: Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 259:735–743. 2014. View Article : Google Scholar : PubMed/NCBI
31	Wang J, Wang X, Lin S, et al: Identification of kininogen-1 as a serum biomarker for the early detection of advanced colorectal adenoma and colorectal cancer. PLoS One. 8:e705192013. View Article : Google Scholar : PubMed/NCBI
32	Biskup K, Braicu EI, Sehouli J, et al: Serum glycome profiling: a biomarker for diagnosis of ovarian cancer. J Proteome Res. 12:4056–4063. 2013. View Article : Google Scholar : PubMed/NCBI
33	Liu R, Chen X, Du Y, et al: Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem. 58:610–618. 2012. View Article : Google Scholar : PubMed/NCBI
34	Eguchi H, Ishikawa O, Ohigashi H, et al: Serum REG4 level is a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer. Pancreas. 38:791–798. 2009. View Article : Google Scholar : PubMed/NCBI
35	Dutta SK, Girotra M, Singla M, et al: Serum HSP70: a novel biomarker for early detection of pancreatic cancer. Pancreas. 41:530–534. 2012. View Article : Google Scholar : PubMed/NCBI
36	Brand RE, Nolen BM, Zeh HJ, et al: Serum biomarker panels for the detection of pancreatic cancer. Clin Cancer Res. 17:805–816. 2011. View Article : Google Scholar : PubMed/NCBI
37	Boeck S, Wittwer C, Heinemann V, et al: Cytokeratin 19-fragments (CYFRA 21-1) as a novel serum biomarker for response and survival in patients with advanced pancreatic cancer. Br J Cancer. 108:1684–1694. 2013. View Article : Google Scholar : PubMed/NCBI
38	Chen X, Ba Y, Ma L, et al: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18:997–1006. 2008. View Article : Google Scholar : PubMed/NCBI
39	Sugiura T, Uesaka K, Mihara K, et al: Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 154:1078–1086. 2013. View Article : Google Scholar : PubMed/NCBI
40	Kitamura K, Seike M, Okano T, et al: MiR-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. Mol Cancer Ther. 13:444–453. 2014.PubMed/NCBI
41	Mackay F and Ambrose C: The TNF family members BAFF and APRIL: the growing complexity. Cytokine Growth Factor Rev. 14:311–324. 2003. View Article : Google Scholar : PubMed/NCBI
42	Lascano V, Zabalegui LF, Cameron K, et al: The TNF family member APRIL promotes colorectal tumorigenesis. Cell Death Differ. 19:1826–1835. 2012. View Article : Google Scholar : PubMed/NCBI
43	Watanabe T, Takahashi A, Suzuki K, et al: Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori. Int J Cancer. 134:2373–2382. 2014.
44	Wang H, Fang R, Wang XF, et al: Stabilization of Snail through AKT/GSK-3β signaling pathway is required for TNF-α-induced epithelial-mesenchymal transition in prostate cancer PC3 cells. Eur J Pharmacol. 714:48–55. 2013.PubMed/NCBI
45	Wang H, Wang HS, Zhou BH, et al: Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS One. 8:e566642013.
46	Techasen A, Namwat N, Loilome W, et al: Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma. Med Oncol. 29:3083–3091. 2012.