Azcue Pablo, Encío Ignacio, Guerrero Setas David, Suarez Alecha Javier, Galbete Arkaitz, Mercado María, Vera Ruth, Gomez-Dorronsoro Maria Luisa
Department of Health Science, Public University of Navarra (UPNA), 31008 Pamplona, Spain.
Institute for Health Research Navarra (IdISNA), 31008 Pamplona, Spain.
Cancers (Basel). 2021 Apr 17;13(8):1943. doi: 10.3390/cancers13081943.
There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting.
Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS).
PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26-0.82), = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS ( = 0.004) and DFS ( < 0.001).
Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.
目前迫切需要更好地对早期结直肠癌(CRC)患者进行特征描述。PD-1配体(PD-L1)表达已被提出作为一种预后因素,但在不同情况下结果不一。共识分子亚型(CMS)分类尚未纳入临床实践。我们试图评估PD-L1表达在早期结肠癌患者总体及CMS分类中的预后价值,以期在此情况下辅助治疗选择。
从162例II/III期CRC患者的肿瘤样本构建组织芯片。对其进行PD-L1及拟议的CMS检测项目的自动免疫组化染色。主要终点为总生存期(OS)和无病生存期(DFS)。
PD-L1表达与较好的预后显著且独立相关(HR = 0.46(0.26 - 0.82),P = 0.009),且大多见于肿瘤相关基质的免疫细胞中。与CMS1相比,CMS4的死亡风险增加五倍(HR = 5.58(1.36,22.0),P = 0.034)。在CMS2/CMS3亚组分析中,PD-L1表达显著区分出OS较好(P = 0.004)和DFS较好(P < 0.001)的个体。
我们的研究表明,PD-L1表达是II/III期结肠癌患者的独立预后因素。此外,它成功区分出CMS2/CMS3组中预后较好的患者,可能对CMS分类的临床相关性具有重要意义。