Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling

Chen, Wei Chao; Li, Qiuli; Pan, Qimei; Zhang, Hua Yong; Xiao, Fu; Fan, Yu; Wang, Jian Ning; Yang, Ankui

doi:10.1186/s13046-019-1155-6

Cited by 30 publications

(23 citation statements)

References 34 publications

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“…We discovered that the SDGs were mainly enriched in the NF−kappaB signaling pathway and DNA repair by GO and KEGG analyses. Several studies have strongly supported the associations between NF−kappaB signaling pathway and HNC [20][21][22] . Qin Y et.al found the CCL18 (chemokine (C-C motif) ligand 18) could promote the HNSCC malignancy and its level was signi cantly associated with histological grade through regulating the NF−κB signal pathway [20] .…”

Section: Discussionmentioning

confidence: 94%

Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

Cao

She

2020

Preprint

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Background: The mechanism of transition from low-grade to high-grade head and neck carcinomas (HNC) still remains unclear. The aim of this study was to explore the genes expression profiles that drive malignancy from low to high-grade HNC, as well as analyze their correlations with the survival.Methods: Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low and high-grade HNC were screened by GEO2R and R software. Bioinformatics functions of SDGs were investigated by the enrichment analyses. Univariate and multivariate cox regressions were performed to identify prognostic SDGs of progression free survival (PFS) and disease specific survival (DSS). ROC curve was established to evaluate the ability to predict the prognosis. Then, the correlations between SDGs and clinical features were evaluated. The genes were experimentally validated by RT-PCR in clinical specimens’ tissues at last.Results: Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Enrichment analysis showed these SDGs were mainly enriched in the DNA repair pathway and the regulation of I−kappaB kinase/NF−kappaB signaling pathway. Cox regression analyses showed that CXCL14, SLC44A1 and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients at a high-risk or low-risk for prognosis were established based on genes signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033, 0.010 respectively). Multivariate cox regression showed HPV (P=0.033), lymph node status (P=0.032) and residual status (P＜0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858, 0.901 respectively). In addition, we found UBD, PPP2R2C and risk score were significantly associated with HPV status (all P＜0.05). The experiment results showed CXCL14 and SLC44A1 were significantly overexpressed in the HNC grade I/II tissues and the UBD were overexpressed in the HNC grade III/IV tissues.Conclusions: Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarker to predict the survival.

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Section: Discussionmentioning

confidence: 94%

Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

Cao

She

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…We discovered that the SDGs were mainly enriched in the NF − kappaB signaling pathway and DNA repair by GO and KEGG analyses. Several studies have strongly supported the associations between NF − kappaB signaling pathway and HNC [20][21][22] . Qin Y et.al found that CCL18 (chemokine (C-C motif) ligand 18) could promote the HNSCC malignancy and its level was signi cantly associated with histological grade through regulating the NF − κB signal pathway [20] .…”

Section: Discussionmentioning

confidence: 95%

“…Furthermore, the NF − κB inhibitor could reduce the invasion of HNSCC cells [21] . In addition, the NF − κB pathway induced by XPR1 was related to many aspects of TSCC (tongue squamous cell carcinoma), including the tumor grade and patients' prognosis [22] . These studies illuminated the functions of NF − κB signal pathway in the HNSCC malignancy in terms of histological grade.…”

Section: Discussionmentioning

confidence: 99%

Identification and Clinical Validation of Genes Signatures with Grade and Survival in Head and Neck Carcinomas

Cao

She

2020

Preprint

View full text Add to dashboard Cite

Background: The mechanism of transition from low-grade to high-grade head and neck carcinomas (HNC) still remains unclear. This study aimed to explore the genes expression profiles that drive malignancy from low to high-grade HNC, as well as analyze their correlations with survival.Methods: Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly different genes (SDGs) between low and high-grade HNC were screened by GEO2R tool and R software. Bioinformatics functions of SDGs were investigated by the enrichment analyses. Univariate and multivariate cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating curve (ROC) was established to evaluate the ability to predict the prognosis. Then, the correlations between SDGs and clinical features were evaluated. The genes were experimentally validated by RT-PCR in clinical specimens.Results: 35 SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Enrichment analysis showed these SDGs were enriched in the DNA repair pathway and the regulation of I−kappaB kinase/NF−kappaB signaling pathway. Cox regression analyses showed that CXCL14, SLC44A1 and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients at a high-risk or low-risk for prognosis were established based on genes signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033, 0.010 respectively). Multivariate cox regression showed human papillomavirus (HPV) (P=0.033), lymph node status (P=0.032) and residual status (P＜0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858, 0.901 respectively). In addition, we found UBD, PPP2R2C and risk score were significantly associated with HPV status (all P＜0.05). The experiment results showed CXCL14 and SLC44A1 were significantly overexpressed in the HNC grade I/II tissues and the UBD was overexpressed in the HNC grade III/IV tissues.Conclusions: Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarker to predict the survival.

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“…However, the underlying molecular mechanism remains unknown. It has been reported that the NF‐kB and the ERK MAPK signaling pathways play an important role in the invasion and metastasis of cancers 16‐19 . Hence, western blotting was carried out to preliminarily test the molecular changes in NF‐kB and the ERK MAPK signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

Upregulation of long non‐coding RNA FOXD2‐AS1 promotes progression and predicts poor prognosis in tongue squamous cell carcinoma

Zhou

Huang

Meng

et al. 2020

J Oral Pathology Medicine

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Background Accumulating evidences suggest that lncRNA FOXD2‐AS1 plays an important role in tumor progression, however, its function in tongue squamous cell carcinoma (TSCC) remains unknown. This research aims to investigate the function and mechanism of FOXD2‐AS1 in the modulation of tongue squamous cell carcinoma progression. Methods Expression of FOXD2‐AS1 was detected in TSCC tissues and TCGA data. Receiver operating characteristic curves (ROCs) analysis and bioinformatic analysis of TCGA data were performed to investigate the role of FOXD2‐AS1 in TSCC prognosis. After siRNA‐mediated downregulation of FOXD2‐AS1, wound healing assay, Transwell migration and invasion assays, and MTS proliferation assay were conducted to explore the effects that FOXD2‐AS1 exerted on SCC‐9 and CAL‐27 cell lines. Western blotting was performed to detect the downstream protein changes. Results Compared to the normal tissues and samples, FOXD2‐AS1 significantly highly expressed in TSCC tissues and in TSCC samples of TCGA data, and high expression of FOXD2‐AS1 was associated with lymphatic metastasis and poor TNM stages. ROC analysis and bioinformatic analysis of TCGA data further suggested that high expression of FOXD2‐AS1 was associated with TSCC poor prognosis. Downregulation of FOXD2‐AS1 inhibited the migration and invasion of SCC‐9 and CAL‐27 cell lines. Western blotting showed that the expression of p‐p44 and p‐p65 downregulated after FOXD2‐AS1 knockdown. Conclusion High expression of FOXD2‐AS1 promotes TSCC progression through modulating NF‐kB and ERK MAPK signaling pathways and is associated with TSCC poor prognosis, it could be a novel therapeutic target and prognostic biomarker for TSCC.

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Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-κB signaling

Cited by 30 publications

References 34 publications

Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

Identification and Clinical Validation of Genes Signatures with Grade and Survival in Head and Neck Carcinomas

Upregulation of long non‐coding RNA FOXD2‐AS1 promotes progression and predicts poor prognosis in tongue squamous cell carcinoma

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