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Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma.

ABSTRACT: Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative. Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation. Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression. Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.

SUBMITTER: Guo SS

PROVIDER: S-EPMC8427601 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma.

Guo Shan-Shan SS Liang Yu-Jing YJ Liu Li-Ting LT Chen Qiu-Yan QY Wen Yue-Feng YF Liu Sai-Lan SL Sun Xue-Song XS Tang Qing-Nan QN Li Xiao-Yun XY Mai Hai-Qiang HQ Tang Lin-Quan LQ

Frontiers in pharmacology 20210826

<b>Background:</b> Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative. <b>Methods:</b> We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogeni ...[more]

PMID: 34512316

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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:BACKGROUND: LATS2, which encodes a novel serine/threonine kinase, is known to be important in centrosome duplication and in the maintenance of genomic stability. Recently, a potential role for LATS2 in cancer has been reported. In breast cancer and acute lymphoblastic leukemia (ALL), LATS2 mRNA is downregulated and has been suggested to be a tumor suppressor. However, the role of LATS2 in nasopharyngeal carcinoma has not been investigated. In this study, we aimed to investigate the expression pattern of LATS2 and its clinicopathological involvement in nasopharyngeal carcinoma to understand its effect on cell survival. METHODS: Using quantitative real time PCR and immunoblotting, the expression of LATS2 was detected in nasopharyngeal carcinoma cell lines and in the immortalized nasopharyngeal epithelial cell line NP69. Using immunohistochemistry, we analyzed LATS2 protein expression in 220 nasopharyngeal carcinoma cases. The association of LATS2 protein expression with the clinicopathological characteristics and the prognosis of nasopharyngeal carcinoma were subsequently assessed. Using methylation specific PCR, we detected the methylation status of the LATS2 promoter. RNA interference was performed by transfecting siRNA to specifically knock down LATS2 expression in 5-8F and CNE2. RESULTS: LATS2 protein was detected in 178 of 220 (80.91%) cases of nasopharyngeal carcinoma. LATS2 overexpression was a significant, independent prognosis predictor (P = 0.037) in nasopharyngeal carcinoma patients. Methylation specific PCR revealed that 36.7% (11/30) of nasopharyngeal carcinoma tissues and all of the chronic nasopharyngeal inflammation samples were methylated. Functional studies showed that the suppression of LATS2 expression in nasopharyngeal carcinoma (5-8F and CNE2) cell lines by using specific small interfering (siRNA) resulted in the inhibition of growth, induction of apoptosis and S-phase cell cycle increase. Overexpression of LATS2 in NP69 stimulated cell proliferation. CONCLUSIONS: Our results indicate that LATS2 might play a role in the tumorigenesis of nasopharyngeal carcinoma by promoting the growth of nasopharyngeal carcinoma cells. Transfection with specific siRNA might be feasible for the inhibition of growth, induction of apoptosis and S phase increase in nasopharyngeal carcinoma.

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Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma.

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Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma.

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