p21 作为直肠癌患者临床结果的预测和预后指标

Li Ching Ooi, Vincent Ho, Jing Zhou Zhu, S. Lim, Liping Chung, Askar Abubakar, Tristan Rutland, Wei Chua, W. Ng, Mark Lee, Matthew Morgan, Scott Mackenzie, Cheok Soon Lee
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引用次数: 0

摘要

p21是一种强效的细胞周期蛋白依赖性激酶抑制剂(CDKI),参与促进细胞周期停滞和调节细胞衰老。直肠癌细胞中 p21 表达的改变可能会影响肿瘤细胞的行为以及对新辅助治疗和辅助治疗的耐受性。我们的研究旨在确定 p21 在直肠癌中的差异表达与患者生存结果之间的关系。我们使用组织芯片对 266 例直肠癌标本进行了 p21 免疫组化染色。分别对肿瘤中心和外围的癌细胞表达模式进行评分,并与临床病理数据、肿瘤回归分级(TRG)、无病生存率和总生存率进行比较。在单变量分析(p = 0.001)和多变量分析(p = 0.003,HR = 2.068)中,肿瘤外围细胞中 p21 的阴性表达与总生存期的延长显著相关。在多变量分析中,肿瘤周边细胞中 p21 负表达也与无病生存期延长有关(p = 0.040,HR = 1.769)。较长的总生存时间还与较低的肿瘤分级(p= 0.011)、无血管和神经周围浸润(p= 0.001; p < 0.005)、无转移(p < 0.005)和辅助治疗(p= 0.009)相关。 p21表达是直肠癌患者临床预后的潜在预测和预后生物标志物。肿瘤周边细胞中 p21 的阴性表达与较长的总生存期和无病生存期有显著相关性。有必要进行更大规模的前瞻性研究,以探讨 p21 是否能识别出将从新辅助治疗和辅助治疗中获益的直肠癌患者。
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p21 as a Predictor and Prognostic Indicator of Clinical Outcome in Rectal Cancer Patients
The cell cycle plays a key and complex role in the development of human cancers. p21 is a potent cyclin-dependent kinase inhibitor (CDKI) involved in the promotion of cell cycle arrest and the regulation of cellular senescence. Altered p21 expression in rectal cancer cells may affect tumor cells’ behavior and resistance to neoadjuvant and adjuvant therapy. Our study aimed to ascertain the relationship between the differential expression of p21 in rectal cancer and patient survival outcomes. Using tissue microarrays, 266 rectal cancer specimens were immunohistochemically stained for p21. The expression patterns were scored separately in cancer cells retrieved from the center and the periphery of the tumor; compared with clinicopathological data, tumor regression grade (TRG), disease-free, and overall survival. Negative p21 expression in tumor periphery cells was significantly associated with longer overall survival upon the univariate (p = 0.001) and multivariable analysis (p = 0.003, HR = 2.068). Negative p21 expression in tumor periphery cells was also associated with longer disease-free survival in the multivariable analysis (p = 0.040, HR = 1.769). Longer overall survival times also correlated with lower tumor grades (p= 0.011), the absence of vascular and perineural invasion (p = 0.001; p < 0.005), the absence of metastases (p < 0.005), and adjuvant treatment (p = 0.009). p21 expression is a potential predictive and prognostic biomarker for clinical outcomes in rectal cancer patients. Negative p21 expression in tumor periphery cells demonstrated significant association with longer overall survival and disease-free survival. Larger prospective studies are warranted to investigate the ability of p21 to identify rectal cancer patients who will benefit from neoadjuvant and adjuvant therapy.
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