Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer.
Prognostic impact of programed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor infiltrating lymphocytes in colorectal cancer.
复制标题
结直肠癌癌细胞和肿瘤浸润淋巴细胞中程序性细胞死亡 1 (PD-1) 和 PD-配体 1 (PD-L1) 表达的预后影响
DOI：
10.1186/s12943-016-0539-x
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发表时间：
2016-08-24
期刊：
影响因子：
37.3
通讯作者：
Cai S
中科院分区：
文献类型：
--
作者：
Li Y;Liang L;Dai W;Cai G;Xu Y;Li X;Li Q;Cai S
结直肠癌（colorectal cancer，CRC）是男性第三大常见癌症，女性第二大常见癌症。PD-1/PD-L1轴作为免疫检查点，在许多肿瘤及其微环境中上调。方法应用癌症基因组图谱（Cancer Genome Atlas，TCGA）数据库（N= 356）和复旦大学上海肿瘤中心（FUSCC）队列研究（N= 276），分析PD-1/PD-L1在结直肠肿瘤细胞（TC）和肿瘤浸润细胞（TIL）中的表达与结直肠癌预后的关系。结果在TCGA队列中，PD-1和PD-L1表达的临界值分别为4.40和2.92。Kaplan-Meier分析显示PD-1和PD-L1表达越高，OS越好（分别为P= 0.032和P = 0.002）。在FUSCC队列中，基于TMA样本（N= 276）通过免疫组织化学（IHC）染色分别分析TILs上的PD-1和TC上的PD-L1表达，并显示TILs-PD-1和TCs-PD-L1均与CRC患者的OS（分别为P= 0.006和P = 0.002）和DFS（分别为P= 0.025和P = 0.004）相关。多因素考克斯回归分析显示TILs-PD-1是影响结直肠癌患者OS和DFS的独立预后因素（P< 0.05）。亚组分析显示，TILs-PD-1是影响MSS熟练亚组结直肠癌患者OS和DFS的独立预后因素（P< 0.05），而在MSS缺乏亚组中，TILs-PD-1和PD-L1均与OS和DFS无关（P> 0.05）。TILs-PD-1是影响结直肠癌患者OS和DFS的独立预后因素，尤其是对MMR熟练亚组。
BackgroundColorectal cancer (CRC) is 3rd most commonly diagnosed cancer in males and the second in females. PD-1/PD-L1 axis, as an immune checkpoint, is up-regulated in many tumors and their microenvironment. However, the prognostic value of PD-1/PD-L1 in CRC remains unclear.MethodsThe Cancer Genome Atlas (TCGA) database (N= 356) and Fudan University Shanghai Cancer Center (FUSCC) cohort of patients (N= 276) were adopted to analyze the prognostic value of PD-L1 in colorectal tumor cells (TCs) and of PD-1 in tumor infiltrating cells (TILs) for CRC. Subgroup analyses were conducted in FUSCC cohort according to patients’ status of mismatch repair.ResultsIn TCGA cohort, the cut-off values of PD-1 and PD-L1 expression were determined by X-tile program, which were 4.40 and 2.92, respectively. Kaplan-Meier analysis indicated that higher PD-1 and PD-L1 expressions correlated with better OS (P= 0.032 andP= 0.002, respectively). In FUSCC cohort, expressions of PD-1 on TILs and PD-L1 on TCs were analyzed separately by immunohistochemistry (IHC) staining based on a TMA sample (N= 276) and revealed that both TILs-PD-1 and TCs-PD-L1 were associated with OS (P= 0.006 andP= 0.002, respectively) and DFS (P= 0.025 andP= 0.004, respectively) of CRC patients. Multivariate Cox regression analysis indicated TILs-PD-1 was an independent prognostic factor both for OS and DFS of CRC patients (P< 0.05). Subgroup analyses showed that TILs-PD-1 was an independent prognostic factor for both OS and DFS in CRC patients in MSS-proficient subgroup (P< 0.05), while neither of them correlated with OS or DFS in MSS-deficient subgroup (P> 0.05).ConclusionsHigher expressions of PD-1 and PD-L1 correlates with better prognosis of CRC patients. TILs-PD-1 is an independent prognostic factor for OS and DFS of CRC patients, especially for MMR-proficient subgroup.