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Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is a type of head and neck tumor with noticeable regional and ethnic differences. It is associated with Epstein-Barr virus infection and has a tendency for local and distant metastasis. NPC is also highly sensitive to radiotherapy and chemotherapy. Over 70% of patients present with locoregionally advanced disease, and distant metastasis is the primary reason for treatment failure. A signal transducer and activator of transcription 3 (STAT3) promotes NPC oncogenesis through mechanisms within cancerous cells and their interactions with the tumor microenvironment, which is critical in the initiation, progression, and metastasis of NPC. Further, p-STAT3 is strongly associated with advanced NPC. Recent research on STAT3 has focused on its expression at the center of various oncogenic pathways. Here, we discuss the role of STAT3 in NPC and its potential therapeutic inhibitors and analogs for the treatment and control of NPC.

SUBMITTER: Si Y

PROVIDER: S-EPMC9615247 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.

Si Yishimei Y Xu Jinjing J Meng Linghan L Wu Yuanqing Y Qi Jianwei J

Frontiers in oncology 20221013

Nasopharyngeal carcinoma (NPC) is a type of head and neck tumor with noticeable regional and ethnic differences. It is associated with Epstein-Barr virus infection and has a tendency for local and distant metastasis. NPC is also highly sensitive to radiotherapy and chemotherapy. Over 70% of patients present with locoregionally advanced disease, and distant metastasis is the primary reason for treatment failure. A signal transducer and activator of transcription 3 (STAT3) promotes NPC oncogenesis ...[more]

PMID: 36313702

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Project description:Identification of cancer-associated genes by genomic profiling contributes to the elucidation of tumor development and progression. The methylthioadenosine phosphorylase (MTAP) gene, located at chromosome 9p21, plays a critical role in tumorigenicity and disease progression in a wide variety of cancers. However, the prognostic impact of MTAP in patients with nasopharyngeal carcinoma (NPC) remains obscured. Through data mining from published transcriptomic database, MTAP was first identified as a differentially downregulated gene in NPC. In this study, our aim was to evaluate the expression of MTAP in NPC and to clarify its prognostic significance.MTAP immunohistochemistry was retrospectively performed and analyzed in biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. The immunoexpression status was correlated with the clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Real-time quantitative polymerase chain reaction (PCR) was used to measure MTAP gene dosage. In some cases, we also performed methylation-specific PCR and pyrosequencing to assess the status of promoter methylation.MTAP deficiency was significantly associated with advanced tumor stages (P = 0.023) and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS. In the multivariate comparison, MTAP deficiency still remained prognostically independent to portend worse DSS (P = 0.021, hazard ratio = 1.870) and DMFS (P = 0.009, hazard ratio = 2.154), together with advanced AJCC stages III to IV. Homozygous deletion or promoter methylation of MTAP gene were identified to be significantly associated with MTAP protein deficiency (P < 0.001).MTAP deficiency was correlated with an aggressive phenotype and independently predictive of worse DSS and DMFS, suggesting its role in disease progression and as an independent prognostic biomarker of NPC, which potentially offers new strategy of targeted treatment for patients lacking MTAP expression.

Dataset Information

Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.

Publications

Role of STAT3 in the pathogenesis of nasopharyngeal carcinoma and its significance in anticancer therapy.

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