Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC

Jia, Lizhou; Wang, Tengqi; Ding, Guofu; Kuai, Xingwang; Wang, Xiaolei; Wang, Bin; Zhao, Wei; Zhao, Yu

doi:10.1016/j.ijbiomac.2020.07.234

Cited by 15 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, TROP2 expression in OSCC was linked to poor outcome in four studies (Fong et al., 2008; Jia et al., 2020; Tang et al., 2018; Zhang et al., 2020), whereas no association with survival or lymph node metastasis was found in another publication (Noorlag et al., 2015). It has been pointed out a significant intratumoral and temporal heterogeneity of TROP2 in virtually every breast and prostate tumor (Remšík et al., 2018), which might also be the case with OSCC and could partially explain these results.…”

Section: Discussionmentioning

confidence: 99%

“…While TROP2 overexpression was reported to worsen prognosis in several solid tumors (Xu et al., 2017; Zeng et al., 2016), the opposite effect or even lack of association with survival was reported in non‐small‐cell lung carcinoma (NSCLC) (Inamura et al., 2017; Mito et al., 2020), hepatocellular carcinoma (Sin et al., 2018), and cervical cancer (Fang et al., 2012). TROP2 overexpression has been associated with shortened overall survival (OS) in OSCC (Fong et al., 2008; Jia et al., 2020; Tang et al., 2018). In contrast, the absence of association between protein expression and survival or lymph node metastasis has been also reported (Noorlag et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas

et al. 2021

View full text Add to dashboard Cite

Background: Trophoblast cell surface antigen 2 (TROP2) has unclear clinical role in oral squamous cell carcinomas (OSCC). Here, we investigated the association of TROP2 immunoexpression with clinicopathological parameters and survival of OSCC patients.Subjects and Methods: Cancer-specific survival (CSS) and disease-free survival (DFS) were assessed in a cohort composed of 266 OSCC. An independent cohort with 88 OSCC samples matched with the normal oral tissue, as well as 17 metastatic lymph nodes, was used for validation.Results: Multivariate analysis showed TROP2 as an independent marker of favorable prognosis for both CSS (HR: 0.60, 95% CI: 0.40-0.90, p = 0.01) and DFS (HR: 0.57, 95% CI: 0.36-0.89, p=0.01). Furthermore, TROP2 protein expression was significantly higher in morphologically normal tissues compared to primary tumors (p<0.0001) and lymph node metastases (p=0.001), and it was significantly associated with CSS (HR: 0.26, 95% CI: 0.09-0.74, p=0.008) in the validation cohort. A pooled mRNA analysis performed on the Oncomine TM database confirmed the underexpression in OSCC compared to normal tissues (p=0.014). Conclusions:In summary, our results point to a favorable prognostic significance of TROP2 overexpression in a large cohort of oral cancer patients, suggesting it as an attractive clinical marker.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Oral squamous cell carcinoma (OSCC) is the commonest head and neck malignancy and responsible for approximately 90% of malignant epithelial tumors in the oral and maxillofacial region [1][2][3][4]. Over the years, comprehensive treatments, which include radiotherapy, chemotherapy, and surgical treatment, have made progress, but poor prognosis remains in OSCC patients, and the 5-year survival rate is roughly 60 [5][6][7][8][9]. Hence, a key to invent effective targeted therapies and improve patient prognosis is uncovering the molecular mechanisms underneath OSCC invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1

Liu

Luo

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

N6-Methyladenosine (m6A) modification is one of the commonest chemical modifications in eukaryotic mRNAs, which has essential effects on mRNA translation, splicing, and stability. Currently, there is a rising concern on the regulatory role of m6A in tumorigenesis. As a known component in the m6A methyltransferase complex, METTL3 (methyltransferase-like 3) plays an essential role in m6A methylation. Till now, the functions of METTL3 in oral squamous cell carcinoma (OSCC) and its relative mechanism remain to be explored. In this research, through the GEPIA database, we found that high METTL3 expression has a correlation with poor prognosis of squamous cell carcinoma of head and neck. qRT-PCR displayed that METTL3 was highly expressed in OSCC cells. Functionally, METTL3 knockdown reduced the invasion, migration, and proliferation competence of OSCC cells and attenuated the activation of CD8+ T cells. In contrast, METTL3 overexpression resulted in opposite results. GEPIA, UALCAN, and SRAMP databases, PCR, western blot, and m6A RNA methylation assay confirmed the m6A modification of PRMT5 and PD-L1 mediated by METTL3. In conclusion, our results displayed that METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and PD-L1, suggesting that METTL3 may be a therapeutic target for OSCC patients.

show abstract

“…Calcium signaling pathway, cytokine-cytokine receptor interaction, ECM receptor interaction, MAPK signaling pathway and VEGF signaling pathway were activated in low-risk samples. Previously, calcium-dependent and cell cycle pathways may mediate OSCC progression ( Jia et al, 2020 ). MAPK ( Jin et al, 2020 ) and VEGF pathways ( Lien et al, 2020 ) enhance OSCC progression.…”

Section: Discussionmentioning

confidence: 99%

Systematic establishment and verification of an epithelial-mesenchymal transition gene signature for predicting prognosis of oral squamous cell carcinoma

Tan

Liu

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Objective: Epithelial-mesenchymal transition (EMT) is linked to an unfavorable prognosis in oral squamous cell carcinoma (OSCC). Here, we aimed to develop an EMT gene signature for OSCC prognosis.Methods: In TCGA dataset, prognosis-related EMT genes with p < 0.05 were screened in OSCC. An EMT gene signature was then conducted with LASSO method. The efficacy of this signature in predicting prognosis was externally verified in the GSE41613 dataset. Correlations between this signature and stromal/immune scores and immune cell infiltration were assessed by ESTIMATE and CIBERSORT algorithms. GSEA was applied for exploring significant signaling pathways activated in high- and low-risk phenotypes. Expression of each gene was validated in 40 paired OSCC and normal tissues via RT-qPCR.Results: A prognostic 9-EMT gene signature was constructed in OSCC. High risk score predicted poorer clinical outcomes than low risk score. ROCs confirmed the well performance on predicting 1-, 3- and 5-year survival. Multivariate cox analysis revealed that this signature was independently predictive of OSCC prognosis. The well predictive efficacy was validated in the GSE41613 dataset. Furthermore, this signature was distinctly related to stromal/immune scores and immune cell infiltration in OSCC. Distinct pathways were activated in two subgroups. After validation, AREG, COL5A3, DKK1, GAS1, GPX7 and PLOD2 were distinctly upregulated and SFRP1 was downregulated in OSCC than normal tissues.Conclusion: Our data identified and verified a robust EMT gene signature in OSCC, which provided a novel clinical tool for predicting prognosis and several targets against OSCC therapy.

show abstract

Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC

Cited by 15 publications

References 26 publications

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas

Trophoblast cell surface antigen 2 expression predicts outcome in oral squamous cell carcinomas

METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1

Systematic establishment and verification of an epithelial-mesenchymal transition gene signature for predicting prognosis of oral squamous cell carcinoma

Contact Info

Product

Resources

About