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Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma.

ABSTRACT: Aims: Programmed cell death ligand 1 (PD-L1) is the ligand of programmed death 1 (PD-1), which is a host immunity inhibitory receptor. Expression of PD-L1 in diverse tumor types has been widely discussed, while there is little research about tumor intrinsic-PD-1. Phospho-S6 (p-S6) is an important downstream effector in the PI3K/AKT/mTOR pathway. Our study was focused on investigating expression of cancer cell-intrinsic PD-1, PD-L1 and p-S6 proteins and aimed to illustrate their relationship and clinical significances in nasopharyngeal carcinoma (NPC). Methods: The expression of PD-1, PD-L1 and p-S6 proteins in tissues of NPC, non-cancerous nasopharyngeal epithelia, primary cancer and matching metastatic lesion was detected by immunohistochemistry. Results: Expression of PD-1, PD-L1 and p-S6 proteins and co-expression of PD-1 and PD-L1 were significantly higher in NPC (all P<0.05). The expression of PD-1 and co-expression of PD-1 and PD-L1 in paired metastatic NPC were significantly increased (all P<0.01). NPC patients with positive expression of PD-L1 showed significantly higher overall survival rate (P =0.035). However, NPC patients with positive expression PD-1 and p-S6 showed significantly lower overall survival rate (P =0.031, P=0.044, respectively). Interestingly, NPC patients with co-expression of PD-1 and PD-L1 had lower overall survival rate (P=0.042). Multivariate Cox proportional hazard regression analysis confirmed that positive expression of PD-L1 and p-S6 were independent prognostic factors for NPC patients. Conclusions: Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 proteins, PD-L1 might serve as a good prognostic biomarker, while p-S6 could be an independent poor prognostic biomarker for NPC patients.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8425204 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma.

Zhang Yuting Y Chen Xianyong X Zheng Hongmei H Zhan Yuting Y Luo Jiadi J Yang Yang Y Ning Yue Y Wang Haihua H Wang Weiyuan W Fan Songqing S

Journal of Cancer 20210824 20

<b>Aims:</b> Programmed cell death ligand 1 (PD-L1) is the ligand of programmed death 1 (PD-1), which is a host immunity inhibitory receptor. Expression of PD-L1 in diverse tumor types has been widely discussed, while there is little research about tumor intrinsic-PD-1. Phospho-S6 (p-S6) is an important downstream effector in the PI3K/AKT/mTOR pathway. Our study was focused on investigating expression of cancer cell-intrinsic PD-1, PD-L1 and p-S6 proteins and aimed to illustrate their relationsh ...[more]

PMID: 34539884

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Project description:AimsEpidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer progression. Somatostatin receptor 2 (SSTR2) is a G-protein-coupled receptor (GPCR) with diverse biological functions in humans, and it is upregulated through the NF-KB signalling pathway in nasopharyngeal carcinomas (NPC). However, no studies have examined the EGFR and SSTR2 in NPC. This study aimed to investigate whether SSTR2 is associated with EGFR and clinicopathological features in NPC.MethodsBioinformatics analysis was performed to assess the correlation between EGFR and SSTR2 based on the GEO database. The expression of SSTR2 and EGFR was evaluated by immunohistochemistry (IHC) in 491 cases of NPC and 50 cases of non-cancerous nasopharyngeal epithelium.ResultsThe bioinformatics analysis and IHC showed a positive correlation between SSTR2 and EGFR in NPC. High expression of SSTR2 and EGFR was significantly increased in NPC patients compared with non-cancerous nasopharyngeal epithelium. High expression of SSTR2 and/or EGFR was associated with a worse outcome and a higher risk of progression. The study found that patients receiving chemoradiotherapy (CR) with high expression of SSTR2, high expression of EGFR, and high coexpression of SSTR2 and EGFR had a poorer prognosis in both progression-free survival (PFS) and overall survival (OS). Interestingly, NPC patients with high expression of SSTR2, high expression of EGFR, high coexpression of EGFR and SSTR2, and EGFR/SSTR2 anyone high expression had a better prognosis with CR combined with targeted therapy. Cox multivariate analysis identified SSTR2 and EGFR as independent poor predictors of PFS.ConclusionOur study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.

Project description:Nasopharyngeal carcinoma (NPC) is the malignant tumor arising from the nasopharynx epithelium with ethnic and geographical distribution preference. Y-box binding protein-1 (YB1) is the highly expressed DNA/RNA-binding protein with cold shock domain, and enhanced YB1 expression was proved to be associated with many kinds of malignant tumors. There is no systematic study about the regulation of YB1 and cell proliferation, migration, invasion and stress granules (SGs) in NPC, and the relationship between YB1 expression and clinical characteristics and prognosis of NPC patients. We analyzed the mRNA expression of YBX1 in head and neck squamous carcinoma (HNSC) and NPC in databases, investigated the functions of YB1 in cell proliferation, migration and invasion and SGs formation of NPC cells, and detected expression of YB1 protein in a large scale of NPC samples and analyzed their association with clinicopathological features and prognostic significance of NPC patients. YBX1 mRNA was significantly high expression in HNSC and NPC by bioinformatic analysis, and higher expression of YBX1 mRNA indicated poorer prognosis of HNSC patients. Clinically, the expression of YB1 in NPC tissues was significantly higher than these in the control nasopharyngeal epithelial tissues. We further found that the expression of YB1 had an evidently positive relation with advanced clinical stages of patients with NPC. The overall survival rates (OS) were significantly lower for NPC patients with positive expression of YB1. Multivariate analysis confirmed that positive expression of YB1 was the independent poorer prognostic factor for patients with NPC. Moreover, compared with the immortalized nasopharyngeal epithelial cell line (NP69), the basal level of YB1 in NPC cell lines was significantly higher. Knocking down YB1 may inhibit Akt/mTOR pathway in NPC cells. Knocking down YB1 by small interfering RNAs can reduce the ability of proliferation, migration, invasion and SGs formation of NPC cells. The expression of YB1 in NPC cell lines or patients with NPC was significantly higher. The high expression of YB1 protein may act as one valuable independent biomarker to predict poor prognosis for patients with NPC. Knocking down YB1 may release the malignant phenotype of NPC cells.

Dataset Information

Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma.

Publications

Expression of cancer cell-intrinsic PD-1 associates with PD-L1 and p-S6 and predicts a good prognosis in nasopharyngeal carcinoma.

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