Profile of sphingolipid-related genes and its association with prognosis highlights sphingolipid metabolism in oral cancer

2021 ◽  
pp. 1-15
Author(s):  
Gabriel da Silva ◽  
Leandro Luongo de Matos ◽  
Luiz Paulo Kowalski ◽  
Marco Kulcsar ◽  
Andreia Machado Leopoldino

BACKGROUND: Sphingolipids are bioactive lipids that play a role in cancer development. However, the clinical role of sphingolipid (SPL)-related genes in oral cancer (OC) remains not fully understood. OBJECTIVE: This study, aimed to examine the mRNA expression of 14 sphingolipid-related genes in oral cancer patients and their implication with clinicopathological features and prognosis. METHODS: qPCR analysis was performed in 50 OC tissues and their matched surgical margins. Next, Kaplan-Meier, Cox regression, and Receiver operating characteristics (ROC) analysis were applied to evaluate the impact of sphingolipid-related genes expression on the prognosis of OC. RESULTS: The genes SET, ACER3, SK1 and S1PR5 were predominantly up-regulated, while ABCG2, S1PR1, ABCB1 and SPNS2 were down-regulated in OC patients. Analyzing the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) data, which are predominantly composed of OC samples, these genes displayed a similar profile. In OC patients, high levels of SK1 were associated with lymph node metastasis, extracapsular invasion, desmoplasia, locoregional relapse, and disease status. Low levels of SPNS2 were associated with lymph node metastasis, perineural invasion, and disease status. Furthermore, OC and HNSC patients with higher SK1 expression demonstrated shorter disease-free survival (p= 0.0037; p= 0.0087), whereas those with lower SPNS2 expression exhibited shorter overall survival (p= 0.051; p= 0.0012). High levels of ACER3 and low levels of S1PR1 were associated with shorter disease-free and overall survival in HNSC patients. CONCLUSION: Several sphingolipid-related genes are deregulated in OC at the mRNA level and are associated with clinicopathological features and presented potencial for the prediction of poor prognosis in OC patients.

2020 ◽  
Vol 91 (2) ◽  
pp. 62-67
Author(s):  
Volkan Karataşlı ◽  
Selçuk Erkılınç ◽  
İlker Çakır ◽  
Behzat Can ◽  
Tuğba Karadeniz ◽  
...  

2016 ◽  
Vol 7 ◽  
pp. JCM.S40549 ◽  
Author(s):  
Masaaki Yokoyama ◽  
Hiroaki Ohnishi ◽  
Kouki Ohtsuka ◽  
Satsuki Matsushima ◽  
Yasuo Ohkura ◽  
...  

Background The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies. Materials and Methods We performed mutational analysis of KRAS, BRAF, PIK3CA, and FBXW7 and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC. Results KRAS mutations were identified in 9 (14%) of the 63 BTC patients; no mutations were detected within the analyzed regions of BRAF, PIK3CA, and FBXW7. EGFR overexpression was observed in 5 (8%) of the 63 tumors, while TP53 overexpression was observed in 48% (30/63) of the patients. Overall survival of patients with KRAS mutation was significantly shorter than that of patients with the wild-type KRAS gene ( P = 0.005). By multivariate analysis incorporating molecular and clinicopathological features, KRAS mutations and lymph node metastasis were identified to be independently associated with shorter overall survival ( KRAS, P = 0.004; lymph node metastasis, P = 0.015). Conclusions Our data suggest that KRAS mutation is a poor prognosis predictive biomarker for the survival in BTC patients.


2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40820
Author(s):  
Ryoko Oi ◽  
Hirotaka Koizumi ◽  
Ichiro Maeda ◽  
Akira Noguchi ◽  
Shinobu Tatsunami ◽  
...  

The double-stranded RNA-binding protein TARBP2 has been suggested to act as an upstream regulator of breast cancer metastasis by destabilizing transcripts of the possible metastasis suppressors amyloid precursor protein (APP) and ZNF395. We examined this hypothesis by immunostaining of TARBP2, APP, and ZNF395 in 200 breast cancer specimens using tissue microarrays and analyzed the relationships between expression levels and clinicopathological parameters and prognosis. Increased TARBP2 overexpression was associated with shorter overall survival and disease-free survival, and increased but not reduced APP expression correlated with lower overall survival and disease-free survival. ZNF395 expression levels had no prognostic value, but reduced expression correlated with reduced lymph node metastasis. There was no significant relationship between TARBP2 overexpression and reduced APP and/or ZNF395 expression. Patients with tumors with higher TARBP2 or APP expression had unfavorable prognoses. Although reduced ZNF395 expression was significantly related to reduced lymph node metastasis, further studies are needed to clarify the role of TARBP2/APP/ZNF395 in breast cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chunyu Zhang ◽  
Jiao Hu ◽  
Huihuang Li ◽  
Hongzhi Ma ◽  
Belaydi Othmane ◽  
...  

Bladder cancer is one of the leading causes of cancer deaths worldwide. Early detection of lymph node metastasis of bladder cancer is essential to improve patients’ prognosis and overall survival. Current diagnostic methods are limited, so there is an urgent need for new specific biomarkers. Non-coding RNA and m6A have recently been reported to be abnormally expressed in bladder cancer related to lymph node metastasis. In this review, we tried to summarize the latest knowledge about biomarkers, which predict lymph node metastasis in bladder cancer and their mechanisms. In particular, we paid attention to the impact of non-coding RNA on lymphatic metastasis of bladder cancer and its specific molecular mechanisms, as well as some prediction models based on imaging, pathology, and biomolecules, in an effort to find more accurate diagnostic methods for future clinical application.


2020 ◽  
Author(s):  
Feng Shi ◽  
Shuo Xiao ◽  
Yanjie Zhao ◽  
Yuchen Li ◽  
Ying Gao ◽  
...  

Abstract Background The present study aimed to investigate the prognostic effect of CD38 in patients with esophageal squamous cell carcinoma (ESCC). Methods We performed a retrospective cohort study by consecutively recruiting 142 patients with ESCC. The clinicopathological features and expression of CD38, CD4, CD8, Ki-67, PD-L1 and PD-1 in tumor and immune cells were independently evaluated by two pathologists. Results CD38 was expressed in immune cells but not tumor cells and the median expression rate of CD38 in immune cells was 60%. Among ESCC patients with perigastric lymph node metastasis, the expression rate of CD38 was not associated with the disease-free survival (p = 0.207), but had a significant association with the overall survival (p = 0.042). The median overall survival was 13 months and not observed among patients with low and high expression rate of CD38, respectively. The crude and adjusted hazard ratio (HR) of high CD38 expression was 0.37 (95%CI 0.14, 0.95) and 0.21 (95%CI 0.06, 0.70). The expression rate of CD38 had a negative correlation with PD-L1 expressed in tumor cells and CD4 expressed in immune cells. Among patients without perigastric lymph node metastasis, the expression rate of CD38 showed a significant association with the disease-free survival (p < 0.05). The median disease-free survival was 45 months and not achieved for patients with high and low expression of CD38; the adjusted HR of high CD38 expression was 2.13 (95%CI 0.85, 5.33). CD38 did not have significant association with the overall survival for patients without perigastric lymph node metastasis. The expression rate of CD38 had a negative correlation with PD-L1 expressed in tumor cells and a positive correlation with PD-L1 expressed in immune cells. Conclusion The high expression rate of CD38 was associated with a better survival for ESCC with perigastric lymph node metastasis. The prognostic effect of CD38 on esophageal cancer should be warranted in future prospective studies.


2020 ◽  
Author(s):  
Yongfeng Li ◽  
Xinmiao Rui ◽  
Daobao Chen ◽  
Haojun Xuan ◽  
Hongjian Yang ◽  
...  

Abstract Background: Long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is a novel oncogene and dysregulated in a variety of human cancers. It has been revealed to be associated with the clinicopathological features and prognosis. However, the prognostic value of AWPPH in various cancers remains unclear. Therefore, we perform this meta-analysis to evaluate the relationship between AWPPH expression and clinical outcomes in human cancers.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR=1.79, 95%CI: 1.44-2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR=2.67, 95%CI: 1.86-3.83, P<0.001) , bigger tumor size (OR=2.64, 95%CI:1.47-4.73, P=0.001), macro-vascular invasion (OR=2.08, 95%CI: 1.04-4.16, P=0.04) and lymph node metastasis (OR=2.68, 95%CI: 1.82-3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding. Conclusions: Upregulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion, and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers.


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