Dataset Information

Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma.

ABSTRACT: Even with the advance of diagnosis and the treatment, the 5-year survival rate for esophageal cancer patients is still poor. The checkpoint protein inhibition provides another choice to improve the survival. The expression of the programmed death ligand-1 (PD-L1) was reported but the clinical relevance remained inconsistent in esophageal cancer. Besides, there were few references about the other ligand, programed death ligand-2 (PD-L2). In this study, we evaluated the expressions of PD-L1 and PD-L2 in patients with esophageal squamous cell carcinoma (ESCC) and assessed their clinical relevance.From 1996 to 2011, 150 patients undergone complete surgical resection for ESCC were enrolled. Clinical data were recorded. Expression of PD-L1 and PD-L2 on cytoplasm in paraffin embedded tumor samples were analyzed by immunohistochemistry staining and scored with a semi-quantitative method.Of the patients, 96 (64.0%) patients had PD-L1 overexpression and 63 (42.0%) had PD-L2 overexpression. There was a correlation between the expression of PD-L1 and PD-L2 (P<0.001). Patients without overexpression of PD-L1, pathological T1-2 and N0 status, pathological stage I-II and no post-operative adjuvant treatment had a better disease free survival (DFS). In multivariate analysis, PD-L1 expression and pathological stage were the independent prognostic factors for DFS. The expression of PD-L2 did not influence the DFS. Although not statistically significant, patients without overexpression of PD-L1 and PD-L2 seem to have a better overall survival (OS).The overexpression of PD-L1 on cytoplasm, not PD-L2, is an independent prognostic factor for DFS in patients with ESCC undergone esophagectomy. However, there is a trend which suggested that patients without overexpression of PD-L1 and PD-L2 had a better OS.

SUBMITTER: Hsieh CC

PROVIDER: S-EPMC6106043 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma.

Hsieh Chih-Cheng CC Hsu Han-Shui HS Li Anna Fen-Yau AF Chen Yann-Jang YJ

Journal of thoracic disease 20180701 7

<h4>Background</h4>Even with the advance of diagnosis and the treatment, the 5-year survival rate for esophageal cancer patients is still poor. The checkpoint protein inhibition provides another choice to improve the survival. The expression of the programmed death ligand-1 (PD-L1) was reported but the clinical relevance remained inconsistent in esophageal cancer. Besides, there were few references about the other ligand, programed death ligand-2 (PD-L2). In this study, we evaluated the expressi ...[more]

PMID: 30174892

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME).MethodsThe transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail.ResultsSix m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells.ConclusionOur study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.

Dataset Information

Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma.

Publications

Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma.

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