Aim: The aim of this study was to evaluate the prognostic significance of the preoperative systemic immune-inflammation index (SII) and to establish a nomogram for prediction of survival of tongue squamous cell carcinoma (TSCC) patients who underwent primary surgery and cervical dissection.Methods: 120 patients diagnosed with TSCC who underwent primary tumor and neck dissection without preoperative treatment were included to develop the nomogram. This model was externally validated in an independent data cohort of 50 TSCC patients. X-tile software was used to identify the optimal cut-off value. Prognostic factors were identified by Univariate and multivariate analyses. A nomogram based on the multivariate analysis results was built to predict the survival rate and calibration curves and concordance index (C-index) were used to determine predictive and discriminatory capacity.Results: The optimal cut-off value was 569×10 9 /L for SII. In the training cohort, a high preoperative SII (>569) was significantly related to tumor size, histological grade, depth of invasion, lymph node density (LND). A Kaplan-Meier survival analysis showed that patients with a lower SII had a significantly better 5-year overall survival (OS) and disease-free survival (DFS) than patients with high SII (80.8% vs. 43.5% and 72.7% vs. 36.2%, respectively, P<0.001). Univariate analyses of training cohort revealed that age, clinical stage, depth of invasion, LND, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and SII were significant prognostic factors for OS. Moreover, the receiver operating characteristics (ROC) curve showed that SII was superior to NLR and PLR for predicting clinical outcomes. However, multivariate analysis found that age, LND, and SII were independent risk factors for OS. The C-index of the nomograms based on independent prognostic factors was 0.716 for OS and 0.723 for DFS. The C-indexes for external validation of OS and DFS were 0.852 and 0.754, respectively. The calibration curves showed good agreement between predicted and actual observations of OS and DFS. Lu et al.
SII Predict Survival of TSCCConclusion: SII can serve as a novel independent prognostic factor for OS and DFS of patients with TSCC. The prognostic nomogram based on SII is a reliable model for predicting survival of patients with TSCC after surgery.
Background: Integrin signalling is involved in cell migration, invasion, proliferation and motility. Integrin α5/ITGA5 is a subunit of Integrin and contributes to the activation of Integrin signalling. The potential role of Integrin α5/ITGA5 in oral squamous cancer remains unknown. The aim of this study was to uncover the effect and mechanism of Integrin α5/ ITGA5 in the progression of oral squamous carcinoma. Method: TCGA database scanning, qRT-PCR, immunohistochemistry and Western blotting assays were used to detect the expression of Integrin α5/ITGA5 in tissues and cell lines. We established stable Integrin α5/ITGA5 overexpressing and Integrin α5/ITGA5 knockdown cell lines. We investigated the biological function and the underlying mechanism of Integrin α5/ ITGA5 through a series of experiments. Results: Integrin α5/ITGA5 was upregulated in cancer tissue, and its levels negatively correlated with the overall survival (OS) of patients. Integrin α5/ITGA5 promoted proliferation, migration and invasion in an oral squamous carcinoma cell line by EMT (epithelialmesenchymal transition). Conclusion: Integrin α5/ITGA5 promotes the proliferation, migration and invasion of oral squamous carcinoma.
The insulin receptor (INSR) and insulin-like growth factor 1 receptor (IGF1R) have been reported to be involved in the tumorigenesis and metastasis of various malignancies. The aim of our study was to investigate and compare the effects of INSR and IGF1R on the tumorigenesis and metastasis of tongue squamous cell carcinoma (TSCC) and explore the possible mechanism(s) involved. We found that INSR had the same up-regulated expression pattern as IGF1R in TSCC tissues. INSR and IGF1R up-regulation were correlated with each other and associated with lymph node metastasis and poor prognosis. Functional studies established that knocking down either INSR or IGF1R dramatically impeded TSCC cell proliferation, migration, and invasion in vitro and tumorigenesis and tumor metastasis in vivo, whereas ectopic overexpression of INSR or IGF1R enhanced these activities. Both INSR and IGF1R directly targeted p65 and activated the NF-κB pathway; furthermore, C-myc was observed to directly bind to the INSR and IGF1R promoters and up-regulates INSR and IGF1R expression in TSCC. Thus, our current data demonstrate that both INSR and IGF1R are directly targeted by C-myc and exert similar effects to promote the tumorigenesis and metastasis of TSCC through the NF-κB pathway. Therefore, INSR and IGF1R may be therapeutic target genes and potential prognostic factors for TSCC.
The glycolytic enzyme hexokinase (HK2), which is aberrantly expressed in various types of tumours, is associated with metastasis. However, its role in the progression and metastasis of tongue squamous cell carcinoma (TSCC) remains unclear. The results of our study showed that HK2 expression is often deregulated in TSCC patients. Increased HK2 expression was associated with tumour stage, clinical stage, lymph node metastasis, but not pathological grade, and reduced overall survival. Microarray and western blotting analyses revealed increases in HK2 expression in TSCC cells with higher metastatic potential. The following effects were observed with HK2 knockdown: inhibition of cell migration and invasion; reduced SOD2 activity and intracellular H2O2 levels; suppression of pERK1/2, Slug and Vimentin expression; and inhibition of tumour growth and lung metastasis in vivo. Conversely, HK2 overexpression promoted cell migration and invasion, increased SOD2 activity and intracellular H2O2, and enhanced expression of pERK1/2, Slug and Vimentin. Thus, our results demonstrate that deregulation of HK2 expression has an important function in the progression of TSCC and may serve as a biomarker of its metastatic potential in TSCC patients. HK2 enhances the metastatic potential of TSCC by stimulating the SOD2-H2O2 pathway.
Oral squamous cell carcinoma (OSCC), the most frequent of all oral cancers, is a type of highly malignant tumors with a high capacity to invade locally and form distant metastases. An increasing number of studies have shown that microRNAs (miRNAs) play an important role in regulating cancer metastasis and invasion. In the present study, we detected the expression of miR-221 in two highly metastatic OSCC cell lines and two OSCC cell lines that are less metastatic using quantitative real-time PCR analysis (qRT-PCR). The qRT-PCR results indicate that miR-221 is upregulated in highly metastatic OSCC cell lines. Then, miR-221 expression was knocked down by transfection with miR-221 inhibitor, and UM1 cell migration and invasion were assessed using transwell migration and invasion assays. The results indicate that inhibition of miR-221 suppressed migration and invasion of UM1 cells. Furthermore, methyl-CpG binding domain protein 2 (MBD2) was identified as a direct target gene of miR-221. Additionally, MBD2 silencing could partly reverse the effect of miR-221 on cell migration and invasion. In conclusion, downregulation of miR-221 inhibits cell migration and invasion at least partially through targeting MBD2 in the human OSCC cell line UM1.
Our results confirm that upregulation of AKT1, a miR-138 target gene, is a frequent event in TSCC and contributes to the aggressive behaviors and poor prognosis of TSCC.
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