High secreted protein acidic and rich in cysteine expression in peritumoral fibroblasts predicts better prognosis in patients with resectable gastric cancer

Nakajima,Masao; Yoshino,Shigefumi; Kanekiyo,Shinsuke; Maeda,Noriko; Sakamoto,Kazuhiko; Tsunedomi,Ryoichi; Suzuki,Nobuaki; Takeda,Shigeru; Yamamoto,Shigeru; Hazama,Shoichi; Hoshii,Yoshinobu; Oga,Atsunori; Itoh,Hiroshi; Ueno,Tomio; Nagano,Hiroaki

doi:10.3892/ol.2017.7418

High secreted protein acidic and rich in cysteine expression in peritumoral fibroblasts predicts better prognosis in patients with resectable gastric cancer

Authors:
- Masao Nakajima
- Shigefumi Yoshino
- Shinsuke Kanekiyo
- Noriko Maeda
- Kazuhiko Sakamoto
- Ryoichi Tsunedomi
- Nobuaki Suzuki
- Shigeru Takeda
- Shigeru Yamamoto
- Shoichi Hazama
- Yoshinobu Hoshii
- Atsunori Oga
- Hiroshi Itoh
- Tomio Ueno
- Hiroaki Nagano
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Affiliations: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755‑8505, Japan, Oncology Center, Yamaguchi University Hospital, Yamaguchi 755‑8505, Japan, Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Yamaguchi 755‑8505, Japan, Department of Diagnostic Pathology, Yamaguchi University Hospital, Yamaguchi 755‑8505, Japan, Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755‑8505, Japan, Department of Surgery, Kawasaki Medical School, Okayama 701‑0192, Japan
Published online on: November 15, 2017 https://doi.org/10.3892/ol.2017.7418
Pages: 803-812
Copyright: © Nakajima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein that may serve an important role in epithelial‑mesenchymal transition. Recent studies have demonstrated that SPARC status is a prognostic indicator in various cancer types; however, its value remains unclear in gastric cancer (GC). In the present study, the localization and prognostic impact of SPARC expression were evaluated in patients with GC. Immunohistochemical analysis of SPARC expression was performed in 117 surgically resected GC specimens, and the localization of SPARC positive cells, as well as the rassociation between SPARC expression and clinicopathological characteristics were evaluated. High SPARC expression was observed in 47 cases; the glycoprotein was localized in the peritumoral fibroblasts, but was rarely observed in the cytoplasm of cancer cells. Heterogeneity of SPARC expression was observed in 52 cases. High stromal SPARC expression was identified to be an independent predictor of more favorable prognosis (overall survival and recurrence free survival) in all patients (P<0.001). On subgroup analysis, this association remained significant in patients who received adjuvant chemotherapy, but not in patients who did not (P<0.001). Stromal SPARC expression predicts better prognosis in GC patients who underwent curative resection; this appears to be associated with improved response to chemotherapy.

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1	Lordick F, Allum W, Carneiro F, Mitry E, Tabernero J, Tan P, Van Cutsem E, van de Velde C and Cervantes A: Unmet needs and challenges in gastric cancer: The way forward. Cancer Treat Rev. 40:692–700. 2014. View Article : Google Scholar : PubMed/NCBI
2	Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, et al: Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 15:1389–1396. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bradshaw AD and Sage EH: SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest. 107:1049–1054. 2001. View Article : Google Scholar : PubMed/NCBI
4	Yin J, Chen G, Liu Y, Liu S, Wang P, Wan Y, Wang X, Zhu J and Gao H: Downregulation of SPARC expression decreases gastric cancer cellular invasion and survival. J Exp Clin Cancer Res. 29:592010. View Article : Google Scholar : PubMed/NCBI
5	Zhang J, Wang P, Zhu J, Wang W, Yin J, Zhang C, Chen Z, Sun L, Wan Y, Wang X, et al: SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells. Oncol Rep. 31:2312–2320. 2014. View Article : Google Scholar : PubMed/NCBI
6	Brekken RA and Sage EH: SPARC, a matricellular protein: At the crossroads of cell-matrix communication. Matrix Biol. 19:816–827. 2001. View Article : Google Scholar : PubMed/NCBI
7	Rivera LB, Bradshaw AD and Brekken RA: The regulatory function of SPARC in vascular biology. Cell Mol Life Sci. 68:3165–3173. 2011. View Article : Google Scholar : PubMed/NCBI
8	Nakashima S, Kobayashi S, Sakai D, Tomokuni A, Tomimaru Y, Hama N, Wada H, Kawamoto K, Marubashi S, Eguchi H, et al: Prognostic impact of tumoral and/or peri-tumoral stromal SPARC expressions after surgery in patients with biliary tract cancer. J Surg Oncol. 110:1016–1022. 2014. View Article : Google Scholar : PubMed/NCBI
9	Nagai MA, Gerhard R, Fregnani JH, Nonogaki S, Rierger RB, Netto MM and Soares FA: Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. Breast Cancer Res Treat. 126:1–14. 2011. View Article : Google Scholar : PubMed/NCBI
10	Mantoni TS, Schendel RR, Rödel F, Niedobitek G, Al-Assar O, Masamune A and Brunner TB: Stromal SPARC expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biol Ther. 7:1806–1815. 2008. View Article : Google Scholar : PubMed/NCBI
11	Yamashita K, Upadhay S, Mimori K, Inoue H and Mori M: Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression. Cancer. 97:2412–2419. 2003. View Article : Google Scholar : PubMed/NCBI
12	Wang HY, Li YY, Shao Q, Hou JH, Wang F, Cai MB, Zeng YX and Shao JY: Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis. J Transl Med. 10:272012. View Article : Google Scholar : PubMed/NCBI
13	Chew A, Salama P, Robbshaw A, Klopcic B, Zeps N, Platell C and Lawrance IC: SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer. PLoS One. 6:e220472011. View Article : Google Scholar : PubMed/NCBI
14	Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, et al: Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: A phase I/II trial. J Clin Oncol. 29:4548–4554. 2011. View Article : Google Scholar : PubMed/NCBI
15	Takeno A, Takemasa I, Doki Y, Yamasaki M, Miyata H, Takiguchi S, Fujiwara Y, Matsubara K and Monden M: Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. Br J Cancer. 99:1307–1315. 2008. View Article : Google Scholar : PubMed/NCBI
16	Tai IT, Dai M, Owen DA and Chen LB: Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy. J Clin Invest. 115:1492–1502. 2005. View Article : Google Scholar : PubMed/NCBI
17	Gao YY, Han RB, Wang X, Ge SH, Li HL, Deng T, Liu R, Bai M, Zhou LK, Zhang XY, et al: Change of SPARC expression after chemotherapy in gastric cancer. Cancer Biol Med. 12:33–40. 2015.PubMed/NCBI
18	Inoue M, Senju S, Hirata S, Ikuta Y, Hayashida Y, Irie A, Harao M, Imai K, Tomita Y, Tsunoda T, et al: Identification of SPARC as a candidate target antigen for immunotherapy of various cancers. Int J Cancer. 127:1393–1403. 2010. View Article : Google Scholar : PubMed/NCBI
19	Zhao ZS, Wang YY, Chu YQ, Ye ZY and Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 16:260–268. 2010. View Article : Google Scholar : PubMed/NCBI
20	Zhang JL, Chen GW, Liu YC, Wang PY, Wang X, Wan YL, Zhu J, Gao HQ, Yin J, Wang W and Tian ML: Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by down-regulating the expression of VEGF and MMP-7 in gastric cancer. PLoS One. 7:e446182012. View Article : Google Scholar : PubMed/NCBI
21	Lee HE, Park KU, Yoo SB, Nam SK, Park DJ, Kim HH and Lee HS: Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer. 49:1448–1457. 2013. View Article : Google Scholar : PubMed/NCBI
22	Jeung HC, Rha SY, Im CK, Shin SJ, Ahn JB, Yang WI, Roh JK, Noh SH and Chung HC: A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy. Cancer. 117:2050–2057. 2011. View Article : Google Scholar : PubMed/NCBI
23	Wang CS, Lin KH, Chen SL, Chan YF and Hsueh S: Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance. Br J Cancer. 91:1924–1930. 2004. View Article : Google Scholar : PubMed/NCBI
24	Franke K, Carl-McGrath S, Röhl FW, Lendeckel U, Ebert MP, Tänzer M, Pross M and Röcken C: Differential expression of SPARC in intestinal-type gastric cancer correlates with tumor progression and nodal spread. Transl Oncol. 2:310–320. 2009. View Article : Google Scholar : PubMed/NCBI
25	Maeng HY, Song SB, Choi DK, Kim KE, Jeong HY, Sakaki Y and Furihata C: Osteonectin-expressing cells in human stomach cancer and their possible clinical significance. Cancer Lett. 184:117–121. 2002. View Article : Google Scholar : PubMed/NCBI
26	Wang L, Yang M, Shan L, Qi L, Chai C, Zhou Q, Yao K, Wu H and Sun W: The role of SPARC protein expression in the progress of gastric cancer. Pathol Oncol Res. 18:697–702. 2012. View Article : Google Scholar : PubMed/NCBI
27	Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, Baik GH, Shibata W, Diprete B, Betz KS, et al: Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 19:257–272. 2011. View Article : Google Scholar : PubMed/NCBI
28	Zhang L, Sah B, Ma J, Shang C, Huang Z and Chen Y: A prospective, randomized, controlled, trial comparing occult-scar incision laparoscopic cholecystectomy and classic three-port laparoscopic cholecystectomy. Surg Endosc. 28:1131–1135. 2014. View Article : Google Scholar : PubMed/NCBI
29	Puolakkainen PA, Brekken RA, Muneer S and Sage EH: Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis. Mol Cancer Res. 2:215–224. 2004.PubMed/NCBI
30	Sinn M, Sinn BV, Striefler JK, Lindner JL, Stieler JM, Lohneis P, Bischoff S, Bläker H, Pelzer U, Bahra M, et al: SPARC expression in resected pancreatic cancer patients treated with gemcitabine: Results from the CONKO-001 study. Ann Oncol. 25:1025–1032. 2014. View Article : Google Scholar : PubMed/NCBI
31	Desai N, Trieu V, Damascelli B and Soon-Shiong P: SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Transl Oncol. 2:59–64. 2009. View Article : Google Scholar : PubMed/NCBI
32	Hidalgo M, Plaza C, Musteanu M, Illei P, Brachmann CB, Heise C, Pierce D, Lopez-Casas PP, Menendez C, Tabernero J, et al: SPARC expression did not predict efficacy of nab-paclitaxel plus gemcitabine or gemcitabine alone for metastatic pancreatic cancer in an exploratory analysis of the phase III MPACT trial. Clin Cancer Res. 21:4811–4818. 2015. View Article : Google Scholar : PubMed/NCBI
33	Schneeweiss A, Seitz J, Smetanay K, Schuetz F, Jaeger D, Bachinger A, Zorn M, Sinn HP and Marmé F: Efficacy of nab-paclitaxel does not seem to be associated with SPARC expression in metastatic breast cancer. Anticancer Res. 34:6609–6615. 2014.PubMed/NCBI