Periostin as a key molecule defining desmoplastic environment in colorectal cancer
Periostin as a key molecule defining desmoplastic environment in colorectal cancer
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DOI：
10.1007/s00428-020-02965-8
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发表时间：
2020-11-19
期刊：
影响因子：
3.5
通讯作者：
Ueno, Hideki
中科院分区：
文献类型：
--
作者：
Sueyama, Takahiro;Kajiwara, Yoshiki;Ueno, Hideki
根据癌症相关成纤维细胞的组织学结果对促纤维增生反应（DR）进行分类被证明是预测结直肠癌（CRC）患者预后的一种有前景的新方法。据报道，癌症相关基质中的骨膜素（POSTN）与不良的临床结果相关。使用抗 POSTN 抗体对 73 名 pStage III CRC 患者（第 1 组）进行免疫组织化学染色。此外，为了评估 POSTN 的 mRNA 和蛋白质表达水平，我们通过定量实时聚合酶链反应和蛋白质印迹分析对 41 名患者（队列 2）的配对正常和侵袭性癌症冷冻标本进行了分析。在队列 1 中，根据 DR 分类，分别有 18、22 和 33 名患者被分为不成熟、中间和成熟。观察到 POSTN 的高免疫反应性分别为 100%、68.2% 和 27.3% (p < 0.0001)。高和低 POSTN 表达亚组的 5 年无复发生存率分别为 56.8% 和 82.7% (p = 0.015)。在队列 2 中，未成熟基质中的 POSTN mRNA 和蛋白质水平显着高于其他 DR 模式的基质。 POSTN 表达与 DR 分类密切相关。 POSTN 可能是导致结直肠癌恶性潜能的关键分子。
Categorizing desmoplastic reaction (DR) based on the histological findings of cancer-associated fibroblasts is shown to be a promising novel method to predict prognosis of patients with colorectal cancer (CRC). Periostin (POSTN) in cancer-associated stroma is reportedly associated with poor clinical outcomes. Immunohistochemical staining with an anti-POSTN antibody was performed in 73 patients with pStage III CRC (cohort 1). In addition, to evaluate mRNA and protein expression levels of POSTN, we analyzed paired normal and invasive cancer frozen specimens by quantitative real-time polymerase chain reaction and western blot analysis in 41 patients (cohort 2). In cohort 1, according to the DR categorization, 18, 22, and 33 patients were classified as immature, intermediate, and mature, respectively. High immunoreactivity of POSTN was observed 100%, 68.2%, and 27.3%, respectively (p < 0.0001). The 5-year relapse-free survival rates were 56.8% and 82.7% in high and low POSTN expression subgroups, respectively (p = 0.015). In cohort 2, the POSTN mRNA and protein levels were significantly higher in the immature stroma as compared to the stroma characterized as other DR patterns. POSTN expression was closely associated with DR categorization. POSTN may be a key molecule that contributes to the malignant potential of CRC.