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Impact of Secreted Protein Acidic and Rich in Cysteine Expression on Prognosis After Surgical Resection for Biliary Carcinoma
Kazuhiro Toyota*, Yoshiaki Murakami, Naru Kondo, Kenichiro Uemura, Naoya Nakagawa, Kazuhide Urabe
Surgery, Applied Life Sciences institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan
Background: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which influences cell migration, proliferation, angiogenesis, matrix cell adhesion, and tissue remodeling. Although reports on some kinds of cancer demonstrated significant association between SPARC expression and chemotherapy effectiveness or prognosis, predictive value of SPARC in biliary carcinoma is still unclear.
Aim: The aim of this study is to investigate whether intratumoral and/or stromal SPARC expression can predict the postoperative survival of patients treated with surgical resection for biliary carcinoma.
Method: A single-institutional retrospective cohort study of all patients having undergone surgical resection for biliary carcinoma between 1998 and 2014 was performed. Intratumoral and stromal SPARC expressions in resected specimen were investigated immunohistochemically in 175 patients with resected stage II - IV biliary carcinoma (19 with intrahepatic cholangiocarcinoma, 62 with hilar cholangiocarcinoma, 51 with distal cholangiocarcinoma, 25 with carcinoma of the gallbladder, and 18 with ampullary carcinoma). The relationship between SPARC expression and clinicopathological factors were compared. In addition, risk factors for poor prognosis after surgery were evaluated using univariate and multivariate analyses.
Result: High SPARC expression of intratumoral and stromal cells was found in 50 (28.6%) and 61 patients (34.9%), respectively. Intratumoral SPARC expression was not related to patient clinicopathological factors. In contrast, stromal SPARC expression was significantly related to location of the tumor (P = 0.044). In all 175 enrolled patients, stromal SPARC expression was significantly associated with OS (P = 0.006), whereas intratumoral SPARC expression was not (P = 0.94). Multivariate analysis revealed that high stromal SPARC expression was identified as an independent risk factor for poor OS (HR: 1.75, P = 0.008). Within a subset of 110 patients who received adjuvant gemcitabine plus S-1 chemotherapy, high stromal expression was associated with poor prognosis (P =0.008). On the other hand, stromal expression did not significantly correlate with OS of patients without adjuvant gemcitabine plus S-1 chemotherapy (P =0.14).
Conclusion: Analysis of stromal SPARC expression enables the stratification of biliary adenocarcinoma patients treated with adjuvant gemcitabine plus S-1 chemotherapy based on their likelihood of OS, and may have a potential to optimize adjuvant chemotherapy for resected biliary carcinoma.
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