Dataset Information

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma.

ABSTRACT:

Background

Tongue squamous cell carcinoma (TSCC) ranks as the most prevalent malignancy in the oral cavity. TSCC patients with occult lymph node metastasis (OLNM) are thought to be at risk of worse outcome. However, regulatory mechanisms underlying OLNM remain less investigated.

Methods

In the present study, CASC18/miR-20a-3p/TGFB2 axis was identified and evaluated by bioinformatic and qRT-PCR analyses. Effects of CASC18 knockdown on cell migration and invasion were determined by wound healing and transwell assays. Western blot, ELISA, RNA pulldown and luciferase reporter assays were performed for mechanism verification.

Results

CASC18 was identified up-regulating in TSCC tumours, and especially in those from patients with OLNM. Importantly, we found higher CASC18 expression was positively correlated with the presence of OLNM and worse outcome of TSCC patients. Furthermore, we demonstrated that CASC18 knockdown repressed cell migration and invasion through inhibiting epithelial-mesenchymal transition, which could be partly rescued by miR-20a-3p inhibitor. Regarding the molecular mechanism, we further confirmed that CASC18 functioned as a ceRNA to sponge miR-20a-3p to enhanceTGFB2 expression and secretion.

Conclusion

In conclusion, we have reported a novel CASC18/miR-20a-3p/TGFB2 ceRNA axis in OLNM of TSCC. Our findings will contribute to a deeper understanding of the molecular mechanism of OLNM in TSCC, and facilitate the development of diagnostic methods for assisting treatment decision-making.

SUBMITTER: Zhou B

PROVIDER: S-EPMC8349069 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveMET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution.MethodsTumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM.ResultsForty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05).ConclusionMET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.