Michal Uhercik1,2, Andrew J Sanders1, Sioned Owen1, Eleri L Davies3, Anup K Sharma2, Wen G Jiang4, Kefah Mokbel5. 1. Cardiff China Medical Research Collaborative, Cardiff University, Cardiff, U.K. 2. St George's University Hospital, London, U.K. 3. Cardiff Breast Centre, University Hospital Llandough, Cardiff and Vale University Health Board, Cardiff, U.K. 4. Cardiff China Medical Research Collaborative, Cardiff University, Cardiff, U.K. jiangw@cf.ac.uk kefahmokbel@hotmail.com. 5. The London Breast Institute, Princess Grace Hospital, London, U.K. jiangw@cf.ac.uk kefahmokbel@hotmail.com.
Abstract
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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Our study demonstrates higher levels of expression of PDL1 are associated with favorable clinical outcome. Copyright
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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Our study demonstrates higher levels of expression of PDL1 are associated with favorable clinical outcome. Copyright
Authors: Timuçin Erol; Nazli Eylem İmamoğlu; Büşra Aydin; Z Ekim Taşkiran; Güneş Esendağli; Kemal Kösemehmetoğlu; Ataç Baykal Journal: Medicine (Baltimore) Date: 2019-08 Impact factor: 1.817