Department of Surgery, Shiga University of Medical Science, Otsu-shi, Shiga, Japan.
Department of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Shiga, Japan.
Ann Surg Oncol. 2019 Dec;26(13):4791-4804. doi: 10.1245/s10434-019-07891-x. Epub 2019 Oct 3.
The tumor microenvironment, including cancer-associated fibroblasts (CAFs), plays various clinical roles in cancer growth. CAFs are a heterogeneous population and express a variety of mesenchymal markers. However, the clinical roles for CAFs expressing different markers in pancreatic ductal adenocarcinoma (PDAC) remain unknown.
We reviewed 67 resected PDAC patients who had not received preoperative therapy. Each primary tumor was analyzed for vimentin and α-smooth muscle actin (α-SMA) expression by immunohistochemical and dual immunofluorescence staining.
There was no correlation between the percentage of cells expressing vimentin and α-SMA in the tumor stroma (Pearson's correlation coefficient: r = 0.171). Higher vimentin expression (p = 0.018) was associated with significantly shorter overall survival in PDAC patients. Using dual immunofluorescence staining, vimentin-positive CAFs were divided into two subpopulations: co-expression of α-SMA, and no co-expression of α-SMA. In PDAC, the level of co-expression had no effect on survival using univariate analysis (median survival time, 33.3 months for low co-expression vs. 18.2 months for high co-expression; log-rank, p = 0.143). However, multivariate analysis clarified that CAFs expressing vimentin alone was an independent predictor of poor survival (p = 0.014; hazard ratio, 2.305; 95% confidence interval, 1.181-4.497).
Vimentin-positive CAFs without co-expression of α-SMA were associated with poor survival in PDAC, and CAFs possessed molecular and functional heterogeneity in this disease.
肿瘤微环境，包括癌相关成纤维细胞（CAFs），在癌症生长中发挥着各种临床作用。CAFs 是一种异质性群体，表达多种间充质标志物。然而，在胰腺导管腺癌（PDAC）中，表达不同标志物的 CAFs 的临床作用尚不清楚。
我们回顾了 67 名未接受术前治疗的接受手术切除的 PDAC 患者。通过免疫组织化学和双重免疫荧光染色分析每个原发肿瘤中波形蛋白和α-平滑肌肌动蛋白（α-SMA）的表达。
肿瘤基质中表达波形蛋白和 α-SMA 的细胞百分比之间没有相关性（皮尔逊相关系数：r=0.171）。PDAC 患者中，波形蛋白表达较高（p=0.018）与总生存期明显缩短相关。使用双重免疫荧光染色，波形蛋白阳性 CAFs 可分为两个亚群：同时表达α-SMA 和不表达α-SMA。在 PDAC 中，使用单因素分析，共表达水平对生存没有影响（低共表达的中位生存时间为 33.3 个月，高共表达的中位生存时间为 18.2 个月；对数秩检验，p=0.143）。然而，多因素分析表明，单独表达波形蛋白的 CAFs 是不良生存的独立预测因子（p=0.014；风险比，2.305；95%置信区间，1.181-4.497）。
不共表达α-SMA 的波形蛋白阳性 CAFs 与 PDAC 的不良生存相关，并且在这种疾病中 CAFs 具有分子和功能异质性。
