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CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma.

ABSTRACT: Background: Through data mining from the public transcriptome of NPC, cyclin-dependent kinase inhibitor 3 (CDKN3) was identified as a significantly upregulated gene in NPC. CDKN3 functions as a key factor in cell cycle regulation. This study was aimed to investigate the expression of CDKN3 in NPC tissues and its prognostic significance. Methods: Immunohistochemistry was performed for 124 NPC patients to assess the protein expression of CDKN3. The stainings of CDKN3 were scored by using H-score method. The relationships between CDKN3 expression status and clinicopathological parameters, disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) were statistically analyzed. Results: High expression of CDKN3 was significantly associated with higher primary nodal status (P=0.030) and higher TNM stage (P=0.019). In univariate analysis, high expression of CDKN3 predicted worse DSS (P<0.0001), DMeFS (P<0.0001), and LRFS (P<0.0001). In multivariate analysis, CDKN3 overexpression still acted as an independent prognostic factor for worse DSS (P<0.001; hazard ratio [HR]=11.999, 95% CI: 5.378-26.771), DMeFS (P<0.001; HR=15.069, 95% CI: 5.884-38.592), and LRFS (P<0.001; HR=5.000, 95% CI: 2.312-10.815). Conclusion: High expression of CDKN3 was an independent negative prognostic factor for NPC and was associated with advanced disease status. It might serve as potential therapeutic target and aid in risk stratification for patients with NPC.

SUBMITTER: Chang SL

PROVIDER: S-EPMC6036165 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma.

Chang Shih-Lun SL Chen Tzu-Ju TJ Lee Ying-En YE Lee Sung-Wei SW Lin Li-Ching LC He Hong-Lin HL

International journal of medical sciences 20180614 10

Background: Through data mining from the public transcriptome of NPC, cyclin-dependent kinase inhibitor 3 (CDKN3) was identified as a significantly upregulated gene in NPC. CDKN3 functions as a key factor in cell cycle regulation. This study was aimed to investigate the expression of CDKN3 in NPC tissues and its prognostic significance. Methods: Immunohistochemistry was performed for 124 NPC patients to assess the protein expression of CDKN3. The stainings of CDKN3 were scor ...[more]

PMID: 30013440

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Project description:BACKGROUND:Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. METHODS:Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. RESULTS:There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR?=?8.5, p?=?<?0.001) and overall survival (OS, HR?=?13, p?=?0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR?=?4.0, p?=?0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p?=?0.008) and low CD3+ TIL (p?=?0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n?=?58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR?=?7.2, p?=?<?0.001) and OS (HR?=?17.3, p?=?0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR?=?6.1, p?=?0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p?<?0.001). CONCLUSIONS:CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3?+?TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

Project description:PurposeTo explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and methodsTILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs-LYM% score = 0), middle-risk group (MRG) (TILs-LYM% score = 1), and low-risk group (LRG) (TILs-LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs-LYM% status with clinicopathological factors and survival, were evaluated.ResultsAs a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan-Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs-LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs-LYM% score was an independent factor affecting survival of the patients, and HRG (TILs-LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs-LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs-LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone.ConclusionsA positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs-LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.

Dataset Information

CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma.

Publications

CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma.

Similar Datasets

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