Epithelial‐Mesenchymal Transition: Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer

Han, Myung Woul; Lee, Mi Kyung; Kim, Young Min; Jeong, Hee; Roh, Jong–Lyel; Choi, Seung‐Ho; Nam, Soon Yuhl; Cho, Kyung–Ja; Kim, Seong Who; Kim, Sang Yoon

doi:10.1177/0194599814556061

Cited by 17 publications

(10 citation statements)

References 38 publications

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“…This result was in agreement to the previous randomised controlled trial showing elective neck dissection showed higher rates of overall and disease-free survival in early staged OTSCC [20]. We did not nd a signi cant correlation with overall survival and vimentin expression unlike the disease-free survival which is similar to previous reports [21]. Positive vimentin expression was found to be associated with increased stage, increased size of the tumour, increased treatment failures, increased locoregional recurrence and poorer disease-free survival.…”

Section: Discussionsupporting

confidence: 93%

“…Positive vimentin expression was found to be associated with increased stage, increased size of the tumour, increased treatment failures, increased locoregional recurrence and poorer disease-free survival. Earlier studies have identi ed vimentin over-expression to be a poor prognostic indicator in OTSCC by univariate analysis [21][22][23][24]. Our study con rms the earlier ndings.…”

Section: Discussionsupporting

confidence: 90%

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Evaluation of Vimentin as a Potential Poor Prognostic Indicator and Salivary Biomarker for Oral Cancers and Pre-Cancers by Mass Spectrometry Based Proteomics

Sivagnanam¹,

Shyamsundar²,

Thangaraj³

et al. 2021

Preprint

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Background : Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer with high morbidity and mortality rates, despite multimodality management. There are currently no clinically relevant molecular markers to help identify patients at a higher risk of recurrence and failure. Methods: 2D-DIGE coupled with tandem mass spectrometry was performed on tissues obtained from early staged OTSCC along with its paired apparently adjacent normal tissue samples (n=10). Top upregulated protein was validated using another independent set of tissue samples by Immunohistochemistry (n=346), comprising of retrospective early stage OTSCC (n=150) and prospective series of oral pre-cancers, normal and oral cancers (n=195). For further validation of protein expression, saliva samples collected from Oral Cancer and pre-cancer samples were analysed by ELISA (n=80). Results: We found vimentin, the mesenchymal protein to be the most upregulated protein in tongue tumour tissues compared to adjacent apparent normal tissues. Vimentin was found to be significantly overexpressed in oral pre-cancers along with cancers compared to normal tissues. Conclusion: Vimentin detection in saliva can be useful diagnostic test to detect oral precancers that may have malignant potential needing closer follow up. Salivary ELISA for vimentin can additionally be useful for disease monitoring in oral cancers.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Evaluation of Vimentin as a Potential Poor Prognostic Indicator and Salivary Biomarker for Oral Cancers and Pre-Cancers by Mass Spectrometry Based Proteomics

Sivagnanam¹,

Shyamsundar²,

Thangaraj³

et al. 2021

Preprint

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“…However, a debate about the optimal cutoff point remains among the published studies. For example, cutoff points of 2 mm [9], 4 mm [3,10], and 5 mm [11] have been used for risk stratification. AJCC has used > 5 mm for upstaging from T1 to T2 and > 10 mm for upstaging to T3.…”

Section: Introductionmentioning

confidence: 99%

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer

et al. 2018

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One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.

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“…Epithelial-mesenchymal transition (EMT), a fundamental process in embryonic development, has been implicated in cancer progression [ 22 – 24 ]. Several molecules, such as JAM-A and EBV-miR-BART7-3p, have been suggested to regulate EMT via the PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

c-Src activation promotes nasopharyngeal carcinoma metastasis by inducing the epithelial-mesenchymal transition via PI3K/Akt signaling pathway: a new and promising target for NPC

Xiang²,

Guo³

et al. 2016

Oncotarget

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Aberrant activation of cellular Src (c-Src), a non-receptor tyrosine kinase, could promote cancer progression through activating its downstream signaling pathways. However, the roles of c-Src and phosphorylated-Src (p-Src) in nasopharyngeal carcinoma (NPC) progression are rarely investigated. Herein, we have identified high c-Src concentrations in the serum of NPC patients with distant metastasis using high-throughput protein microarrays. Levels of c-Src in serum and p-Src in human primary NPC samples were unfavorable independent prognostic factors for cancer-specific survival, disease-free survival, and distant metastasis-free survival. Depletion or inactivation of c-Src in NPC cells using sgRNA with CRISPR/Cas9 system or PP2 decreased cell viability, colony formation, migration and invasion in vitro and metastasis in vivo. In contrast, these malignancies could be up-regulated by overexpressed c-Src in a NPC cell line with low-metastasis potential. Furthermore, p-Src was involved in promoting NPC cell metastasis by inducing the epithelial-mesenchymal transition (EMT) process via activating the PI3K/Akt pathway and cytoskeleton remodeling. The p-Src-induced EMT process could be retarded by PP2, which mediated by down-regulating the PI3K/Akt pathway. In conclusion, elevated levels of c-Src in serum and p-Src in primary NPC tissue correlated with poor outcomes of NPC patients. And aberrant activation of c-Src facilitated NPC cells with malignant potential, especially metastasis ability, which mediated by the PI3K/Akt pathway activation and sequentially induced the EMT process. These findings unveiled a promising approach for targeted therapy of advanced NPC.

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Epithelial‐Mesenchymal Transition: Clinical Implications for Nodal Metastasis and Prognosis of Tongue Cancer

Abstract: Our study reveals that EMT expression is a significant biomarker for predicting lymph node metastasis and tumor recurrence in tongue cancer. Evaluation of EMT expression in tongue cancer can allow therapy to be offered accordingly.

Cited by 17 publications

References 38 publications

Evaluation of Vimentin as a Potential Poor Prognostic Indicator and Salivary Biomarker for Oral Cancers and Pre-Cancers by Mass Spectrometry Based Proteomics

Evaluation of Vimentin as a Potential Poor Prognostic Indicator and Salivary Biomarker for Oral Cancers and Pre-Cancers by Mass Spectrometry Based Proteomics

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer

c-Src activation promotes nasopharyngeal carcinoma metastasis by inducing the epithelial-mesenchymal transition via PI3K/Akt signaling pathway: a new and promising target for NPC

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