Uhercik Michal, Sanders Andrew J, Owen Sioned, Davies Eleri L, Sharma Anup K, Jiang Wen G, Mokbel Kefah
Cardiff China Medical Research Collaborative, Cardiff University, Cardiff, U.K.
St George's University Hospital, London, U.K.
Anticancer Res. 2017 Aug;37(8):4249-4254. doi: 10.21873/anticanres.11817.
BACKGROUND/AIM: Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial.
Quantitative polymerase chain reaction was used to determine transcript expression levels of PD1 and PDL1 in a cohort consisting of primary breast cancer tissues (n=127) and matching non-neoplastic background tissues (n=33) with available clinical and pathological information. Two-sample two-tailed t-test, Kaplan-Meier survival analysis and Wilcoxon tests were performed.
Significant PDL1 transcript level reductions were seen in patients who developed metastases, as well as those who had local recurrence, compared to patients who remained disease-free. Higher PDL1 transcript levels were also associated with better overall and disease-free survival. Significantly higher transcript expression levels of PD1 were found in tumor tissue, whilst a general increase in PDL1 expression was found in tumor tissues, although this did not reach statistical significance.
Our study demonstrates higher levels of expression of PDL1 are associated with favorable clinical outcome.
背景/目的：程序性死亡蛋白1（PD1）及其配体程序性死亡配体1（PDL1）形成一条通路，该通路被激活时被认为会导致抗肿瘤适应性反应受到抑制，从而影响抗肿瘤免疫。随着针对PDL1的潜在靶向治疗方法的出现，我们研究了PD1和PDL1 mRNA表达水平在我们的乳腺癌队列中的临床意义，以探讨其与疾病进展和预后的关联。先前评估PD1和PDL1（mRNA或蛋白质）表达及其与乳腺癌预后关联的研究显示出正相关和负相关，因此仍存在争议。
采用定量聚合酶链反应来测定由原发性乳腺癌组织（n = 127）和匹配的非肿瘤背景组织（n = 33）组成的队列中PD1和PDL1的转录表达水平，这些组织具有可用的临床和病理信息。进行了双样本双尾t检验、Kaplan-Meier生存分析和Wilcoxon检验。
与无疾病复发的患者相比，发生转移的患者以及出现局部复发的患者中，PDL1转录水平显著降低。较高的PDL1转录水平也与更好的总生存期和无病生存期相关。在肿瘤组织中发现PD1的转录表达水平显著更高，而在肿瘤组织中发现PDL1表达普遍增加，尽管这未达到统计学意义。
我们的研究表明，较高水平的PDL1表达与良好的临床结局相关。
