Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection.
Highly aligned stromal collagen is a negative prognostic factor following pancreatic ductal adenocarcinoma resection.
复制标题
DOI：
10.18632/oncotarget.12772
复制
发表时间：
2016-11-15
期刊：
影响因子：
--
通讯作者：
Eliceiri KW
中科院分区：
文献类型：
--
作者：
Drifka CR;Loeffler AG;Mathewson K;Keikhosravi A;Eickhoff JC;Liu Y;Weber SM;Kao WJ;Eliceiri KW
胰腺导管腺癌（PDAC）术后进展的风险因素尚不明确，需要更多的预后因素来为治疗方案和治疗靶点提供依据。PDAC的特征是细胞外基质高度硬化，癌细胞、纤维状胶原蛋白以及其他基质成分之间的相互作用在疾病进展中起着不可或缺的作用。基质胶原蛋白排列的变化已被证明可调节癌细胞的行为，并且在其他癌症类型中具有重要的临床价值，但对于其在PDAC中的作用及其预后价值知之甚少。我们假设胶原蛋白的排列与PDAC患者的生存相关。为了研究这一点，我们对114例接受根治性手术的经病理证实的PDAC患者的组织进行了回顾性二次谐波（SHG）显微镜成像，使用纤维分割算法进行量化，并与患者的生存情况相关联。使用互补的免疫组织化学染色和可视化技术对相同的组织区域进行上皮 - 间质转化（EMT）、α - 平滑肌肌动蛋白（α - SMA）和多配体聚糖 - 1（syndecan - 1）分析。我们发现胶原蛋白排列在肿瘤间存在显著差异，并且在12%的患者队列中观察到胶原蛋白排列明显较高。根据胶原蛋白排列对患者进行分层显示，高排列是PDAC切除术后的一个独立的不良因素（p = 0.0153，多变量分析）。我们还发现EMT的上皮表达以及α - SMA和syndecan - 1的基质表达与胶原蛋白排列呈正相关。总之，基质胶原蛋白排列可能为PDAC肿瘤提供额外的、具有临床相关性的信息，并强调了基质 - 癌症相互作用的重要性。
Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value. We hypothesized that the alignment of collagen is associated with PDAC patient survival. To address this, pathology-confirmed tissues from 114 PDAC patients that underwent curative-intent surgery were retrospectively imaged with Second Harmonic Generation (SHG) microscopy, quantified with fiber segmentation algorithms, and correlated to patient survival. The same tissue regions were analyzed for epithelial-to-mesenchymal (EMT), α-SMA, and syndecan-1 using complimentary immunohistostaining and visualization techniques. Significant inter-tumoral variation in collagen alignment was found, and notably high collagen alignment was observed in 12% of the patient cohort. Stratification of patients according to collagen alignment revealed that high alignment is an independent negative factor following PDAC resection (p = 0.0153, multivariate). We also found that epithelial expression of EMT and the stromal expression of α-SMA and syndecan-1 were positively correlated with collagen alignment. In summary, stromal collagen alignment may provide additional, clinically-relevant information about PDAC tumors and underscores the importance of stroma-cancer interactions.