Predictive and prognostic value of PDL1 protein expression in breast cancer patients in neoadjuvant setting

Wu, Ziping; Zhang, Lei; Peng, Jing; Xu, Shuguang; Zhou, Liheng; Lin, Yanpin; Wang, Yan; Lu, Jinglu; Yin, Wen

doi:10.1080/15384047.2019.1583533

Cited by 21 publications

(23 citation statements)

References 25 publications

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“…In our study, G5 response to NACT in breast cancer was significantly associated with TCs PD-L1 positivity in pretreatment biopsies both in the total breast cancer population and in luminal subtype. Similar to other studies that used IHC technology, PD-L1 protein expression in TCs was found to be a predictive biomarker of pCR both in hormone receptor-positive patients and all 94 locally advanced breast cancer patients treated with NACT(with paclitaxel plus cisplatin weekly regimens, which was not the preferred therapy) by both univariate and multivariate logistic regression analysis [27]. However, the predictive value of PTLCs PD-L1 expression for pCR was not analyzed, and the molecular subtypes and nodal status were not included in the analysis, which were included in our study.…”

Section: Discussionsupporting

confidence: 65%

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer

Han

et al. 2020

Oncol Res Treat

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Background and Objective: The aim of this study was to investigate the value of programmed death ligand 1 (PD-L1) expression as a predictive biomarker for Miller/Payne grading before neoadjuvant chemotherapy (NACT) in breast cancer. Patients and Methods: The expression of PD-L1 in pretreatment biopsies of breast cancer was assessed by immunohistochemistry in tissue microarrays. The results were analyzed using SPSS 22.0 statistical software. Results: Of 53 female patients, 10 (18.9%) patients had a grade 5 (G5) response, and 12 (22.6%) patients showed PD-L1 expression, including 7 (13.2%) patients with staining in tumor cells (TCs) and 8 (15.1%) patients with staining in peritumoral lymphocytes (PTLCs). Logistic regression analysis revealed that G5 response to NACT was significantly associated with TCs or PTLCs PD-L1 positivity, whether with univariate analysis (TCs PD-L1: p = 0.00, OR 20.50, 95% CI 3.11–134.94; PTLCs PD-L1: p = 0.02, OR 6.50, 95% CI 1.27–33.20) or with multivariate analysis (TCs PD-L1: p = 0.00, OR 42.23, 95% CI 3.36–530.90; PTLCs PD-L1: p = 0.02, OR 9.07, 95% CI 1.37–60.02). The same trend was found in the luminal subgroup analysis (TCs PD-L1: p = 0.02, OR 23.43, 95% CI 1.66–331.58; PTLCs PD-L1: p = 0.01, OR 47.89, 95% CI 2.47–927.41). Conclusion: G5 response to NACT in breast cancer was significantly associated with TCs or PTLCs PD-L1-positive expression in pretreatment biopsies; it can be expected that PD-L1 will become a new independent biomarker of response to NACT in breast cancer.

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Section: Discussionsupporting

confidence: 65%

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer

Han

et al. 2020

Oncol Res Treat

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“…On contrary, PD-L1 expression has been reported to be associated with worse prognosis of triple negative breast cancer patients, which counteract effect of tumor-infiltrating lymphocytes [10]. Response of BC patients to neoadjuvant therapy and survival outcome indicated that PD-L1 predicted better rate of pathological complete response (pCR) [26]. In addition, PD-1/PD-L1 correlated genes such as CD5, CD74, CD96 and CD226 were also related with prognosis of BC patients.…”

Section: Discussionmentioning

confidence: 99%

PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer

Cui

Cao

et al. 2019

Cancer Cell Int

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Background Immunotherapies that targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have obtained prominent success in breast cancer (BC). However, not all the patients benefit from the antibody therapy. This study aimed to identify PD-1/PD-L1 correlated genes and pathways as well as investigate their potential as prognostic marker in BC. Materials and methods By analysing transcriptional data of BC from TCGA, we identified PD-1 and PD-L1 correlated genes by WGCNA analysis and explored the biological process as well as pathways they enriched. Co-expression analysis were performed for PD-1/PD-L1 with immune infiltration and checkpoints. The prognostic value of PD-1 and PD-L1 were also investigated. Results PD-1 and PD-L1 expression showed significant difference in different molecular subtypes and stages. PD-1 correlated genes enriched in T cell activation, lymphocyte activation, leukocyte migration while PD-L1 correlated genes demonstrated enrichment including T cell apoptotic process, tolerance induction and cytolysis. Immune infiltration analysis suggested that PD-1 and PD-L1 were related with Neutrophils (r = 0.65, r = 0.48) and Fibroblasts (r = 0.59, r = 0.47). For immune checkpoints analysis, PD-1 was associated with HLA-A (r = 0.804) and INPP5D (r = 0.782) while PD-L1 correlated with CTLA4 (r = 0.843) and CD27 (r = 0.823). PD-1 was associated favorable survival of BC (HR = 0.67, P = 0.012) while PD-L1 did not demonstrate significant association with BC prognosis (HR = 0.85, P = 0.313). Conclusion PD-1 and PD-L1 correlated genes participated in biological process including T cell activation, lymphocyte activation, leukocyte migration, T cell apoptotic process, tolerance induction and cytolysis. PD-1/PD-L1 expression also demonstrated relation with immune infiltration and immune checkpoints. High PD-1 expression predicted better survival of breast cancer patients.

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“…Exosomal microRNAs (miRNAs), which are transferred by EVs, are promising and reliable tools for cancer diagnosis and clinical application [18]. PD-L1 overexpression has been examined as a prognostic factor in diverse cancers including lung cancer [19], gastric cancer [20], ovarian cancer [21], breast cancer [22], prostate cancer [23], bladder cancer [24], cervical cancer [25], cholangiocarcinoma [26], colorectal cancer [27], nasopharyngeal carcinoma [28], diffuse large B-cell lymphoma [29], pancreatic cancer [30], soft-tissue sarcoma [31], renal cell carcinoma [32], and head and neck squamous cell carcinoma [33]. In addition, in patients with melanoma, exosomal PD-L1 is an indicator of immune activation early after the initiation of treatment with immune checkpoint inhibitors (ICIs) and is associated with clinical response to ICIs [34].…”

Section: Introductionmentioning

confidence: 99%

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

Yang

Shui

et al. 2020

Cancer Cell Int

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Background: Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a metaanalysis to identify the prognostic role of PD-L1 in melanoma. Methods: A thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg's test and Egger's test. Results: Thirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57-1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43-1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22-0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90-1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51-1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06-4.83, P = 0.592). Conclusions: This meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

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Predictive and prognostic value of PDL1 protein expression in breast cancer patients in neoadjuvant setting

Cited by 21 publications

References 25 publications

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer

A Potential Predictive Biomarker for Miller/Payne Grading: PD-L1 Expression before Neoadjuvant Chemotherapy in Breast Cancer

PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients

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