Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma
Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma
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DOI：
10.1200/jco.2006.07.8824
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发表时间：
2007-01-20
影响因子：
45.3
通讯作者：
Goggins, Michael
中科院分区：
文献类型：
--
作者：
Infante, Jeffrey R.;Matsubayashi, Hiroyuki;Goggins, Michael
目的 SPARC（富含半胱氨酸的酸性分泌蛋白）是一种参与细胞基质相互作用、伤口修复和细胞迁移的蛋白质，据报道可以抑制癌症生长。 SPARC 在许多胰腺癌中经历表观遗传沉默，但与浸润性胰腺腺癌相邻的基质成纤维细胞经常表达 SPARC。我们评估了胰腺腺癌患者中肿瘤和瘤周 SPARC 表达的预后意义。 患者和方法 通过免疫组织化学方法对来自约翰·霍普金斯医院接受胰十二指肠切除术的患者的 299 例原发性胰腺导管腺癌切除标本中的 SPARC 表达模式进行了表征。 （马里兰州巴尔的摩）1998 年至 2003 年间。Kaplan-Meier 分析和 Cox 比例风险回归模型用于评估与肿瘤 SPARC 存在或不存在以及瘤周 SPARC 状态相关的死亡风险。结果通过 Kaplan-Meier 分析，胰腺癌基质成纤维细胞表达 SPARC 的患者（中位生存期，15 个月）的死亡风险明显较差 预后优于肿瘤基质不表达 SPARC 的患者（中位生存期，30 个月；对数秩 P < .001）。相反，胰腺癌细胞中 SPARC 的表达与预后无关（对数秩 P = 0.13）。控制其他预后因素（肿瘤大小、阳性淋巴结、切缘状态、肿瘤分级和年龄），基质表达 SPARC 的患者与基质不表达 SPARC 的患者相比，相对风险为 1.89（95% Cl，1.31 至 2.74）；胰腺癌细胞中SPARC的表达仍然与预后无关（相对危险度，1.02；95％Cl，0.73至1.42）。结论瘤周成纤维细胞表达SPARC预示着胰腺癌患者的预后较差。
Purpose SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma.Patients and Methods The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status.Results By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% Cl, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% Cl, 0.73 to 1.42).Conclusion The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.