Background/Objectives:Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been reported to be closely associated with tumor progression in various types of cancer, including colorectal cancer (CRC). Periostin, a matricellular protein, was reported to be expressed on both cancer cells and surrounding tumor stromal cells, such as CAFs, and is regulated by Smad2/3 signaling. In this study, we aimed to clarify the clinicopathologic significance of periostin and Smad2/3 expression in CRC, with a particular focus on the tumor microenvironment.Methods:A total of 351 CRC patients were enrolled according to the inclusion and exclusion criteria. The expressions of periostin and Smad2/3 in the tumor specimens were examined by immunohistochemistry.Results:Periostin expression of CAFs and cancer cells in the 351 CRC cases was observed at 36.8% and 0.6%, respectively. Smad2/3 expression of CAFs and cancer cells was observed in 41.0% and 90.0%, respectively. In CAFs, high periostin expression was significantly correlated with high Smad2/3 expression, increased invasion depth, lymph node metastasis, venous invasion, advanced disease stage, and a higher rate of relapse. The prognoses of patients with periostin-positive CAFs were significantly poorer than those with periostin-negative CAFs (p< 0.001). The survival outcomes of stage 3 CRC patients with co-expression of periostin and Smad2/3 were significantly worse compared to those with stage 2 CRC. In the stage 3 group, multivariate analysis revealed that periostin was an independent prognostic factor, while univariate analysis showed that both periostin and Smad2/3 were significantly correlated with poor survival.Conclusions:These findings suggest that periostin is expressed mainly in CAFs in CRC and is correlated with Smad2/3 expression in CAFs. Periostin from CAFs might be associated with the malignant progression of CRC via Smad2/3 signaling.
背景/目的：肿瘤微环境中的癌症相关成纤维细胞（CAFs）已被报道与包括结直肠癌（CRC）在内的多种癌症的肿瘤进展密切相关。骨膜蛋白作为一种基质细胞蛋白，据报道在癌细胞及周围肿瘤基质细胞（如CAFs）中均有表达，并受Smad2/3信号通路调控。本研究旨在阐明骨膜蛋白与Smad2/3在结直肠癌中表达的临床病理学意义，并特别关注其在肿瘤微环境中的作用。 方法：根据纳入与排除标准，共纳入351例结直肠癌患者。通过免疫组织化学方法检测肿瘤标本中骨膜蛋白与Smad2/3的表达情况。 结果：在351例结直肠癌病例中，CAFs与癌细胞的骨膜蛋白表达率分别为36.8%和0.6%。CAFs与癌细胞的Smad2/3表达率分别为41.0%和90.0%。在CAFs中，骨膜蛋白高表达与Smad2/3高表达、浸润深度增加、淋巴结转移、静脉侵犯、疾病分期较晚及较高复发率显著相关。骨膜蛋白阳性CAFs患者的预后显著差于骨膜蛋白阴性患者（p<0.001）。在同时表达骨膜蛋白与Smad2/3的3期结直肠癌患者中，其生存结局显著差于2期患者。在3期患者组中，多变量分析显示骨膜蛋白是独立的预后因素，而单变量分析表明骨膜蛋白与Smad2/3均与不良生存率显著相关。 结论：这些发现表明，骨膜蛋白主要在结直肠癌的CAFs中表达，并与CAFs中Smad2/3的表达相关。CAFs来源的骨膜蛋白可能通过Smad2/3信号通路参与结直肠癌的恶性进展。
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