Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis.
Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis.
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DOI：
10.1080/2162402x.2018.1465165
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发表时间：
2018
期刊：
影响因子：
7.2
通讯作者：
Jirström K
中科院分区：
文献类型：
--
作者：
Berntsson J;Eberhard J;Nodin B;Leandersson K;Larsson AH;Jirström K
程序性细胞死亡蛋白1 （PD-1）及其配体PD-L1的表达已被证明在结直肠癌（CRC）中具有预后价值，但尚未有研究调查这种关联是否因肿瘤位置而异。在这项研究中，我们分析了557例CRC患者原发肿瘤组织微阵列中PD-1和PD-L1的免疫组织化学表达。采用单变量和多变量Cox回归分析，调整年龄、性别、TNM分期、分化等级和血管侵犯，以确定生物标志物表达对整个队列以及右结肠、左结肠和直肠的5年总生存率（OS）的影响。在整个队列中，肿瘤浸润性免疫细胞上PD-L1的高表达是延长OS的独立因素（风险比[HR] = 0.49； 95%可信区间[CI] CI 0.35 - 0.68），以及右结肠肿瘤（HR = 0.43; 95% CI 0.25 - 0.74）和左结肠肿瘤（HR = 0.28; 95% CI 0.13 - 0.61），但在直肠癌中没有。肿瘤特异性pd - l1表达不具有预后，无论是在整个队列中还是根据肿瘤位置。在整个队列和右结肠肿瘤中，高免疫细胞特异性PD-1表达与延长的OS相关，但在左结肠或直肠中没有，并且仅在单变量分析中。总之，这些结果表明，免疫细胞特异性PD-L1和PD-1表达以位点依赖的方式影响CRC的预后，而肿瘤特异性PD-L1表达不影响CRC的预后。
Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.