Abstract:
:Objectives: PD-1 and PD-L1 overexpression in malignant tumors in response to radiotherapy is correlated with a poor prognosis. Human papilloma virus (HPV) infection impacts intrinsic radiosensitivity of head and neck cancers (HNCs). Herein, this study aims to determine PD-1/PD-L1 expression differences in tumors with different HPV statuses and their prognostic value in patients with different radiosensitivity gene signatures to define the characteristics of patients who will benefit from radiotherapy combined with anti-PD-1/PD-L1 therapy. Material and methods: According to the identified gene signature related to radiosensitivity, 517 patients from the TCGA HNSCC cohort were selected and divided into the radioresistant (RR) group and radiosensitive (RS) group using a K-mean clustering algorithm. All data analyses were conducted using SPSS and GraphPad Prism. Results: PD-L1 expression is upregulated in tumor tissue (unpaired t test, P=0.0363; paired t test, P=0.0584) compared with normal tissue. PD-L1 was positively correlated with PD-1 expression (P<0.0001). The HPV/p16-positive group was significantly high PD-1 expression (P<0.0001). PD-L1 expression (P=0.0005) and PD-1 expression (P<0.0001) were significantly increased in the RS group compared with that in the RR group. In the patients who were treated with radiotherapy, the PD-1-high group was associated with better recurrence-free survival (RFS) (HR, 0.4892; 95% CI, 0.2357-1.015; P=0.023). Within the RR group, high PD-L1 expression was associated with reduced overall survival (OS) (HR, 2.196; 95% CI, 1.081-4.46; P=0.0108) compared with low PD-L1 expression. In the RR group, HPV/p16-negative patients with high PD-L1 expression exhibited reduced OS (HPV: HR, 2.334; 95% CI, 0.7828-6.961; P=0.0313; p16: HR,2.486; 95% CI, 0.8559-7.219; P=0.0192) compared with that of patients with low PD-L1 expression. In the PD-L1-high group, RR patients exhibited reduced OS (HR, 0.4858; 95% CI, 0.2136-1.105; P=0.0189) and RFS (HR, 0.4371; 95% CI, 0.1421-1.345; P=0.0231) compared with that of RS patients. Conclusion: Our findings demonstrated that high PD-1/PD-L1 expression was strongly related to radiosensitivity, and high PD-1 expression was significantly associated with HPV/p16-positive HNCs. Patients in the radioresistant group and patients in the HPV/p16-negative group with a radioresistant gene signature could benefit from the combination of radiotherapy and anti-PD-1/PD-L1 therapy.
journal_name
J Cancerjournal_title
Journal of Cancerauthors
Lyu X,Zhang M,Li G,Jiang Y,Qiao Qdoi
10.7150/jca.27199subject
Has Abstractpub_date
2019-01-29 00:00:00pages
937-948issue
4issn
1837-9664pii
jcav10p0937journal_volume
10pub_type
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abstract::Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We sear...
journal_title:Journal of Cancer
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更新日期:2018-09-08 00:00:00
abstract::Clinical outcomes of checkpoint blockade immunotherapy on colorectal cancer (CRC) are influenced by mismatch repair (MMR) gene status, which is associated with distinct tumor immune infiltrates and systemic inflammatory response status. However, the prognostic value of PD-L1 expression and the systemic inflammatory re...
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journal_title:Journal of Cancer
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