Identification of ITGA3 as an Oncogene in Human Tongue Cancer via Integrated Bioinformatics Analysis

Human tongue cancer （TC） is an aggressive malignancy with a very poor prognosis. There is an urgent need to elucidate the underlying molecular mechanisms involved in TC progression, mRNA expression profiles play a vital role in the exploration of cancer-related genes. Therefore, the purpose of our study was to identify the progression associated candidate genes of TC by bioinformatics analysis. Five microarray datasets of TC samples were downloaded from the Gene Expression Onmibus （GEO） database and the data of 133 TC patients were screened from The Cancer Genome Atlas （TCGA） head and neck squamous cell carcinoma （HNSC） database. The integrated analysis of five microarray datasets and the RNA sequencing data of TC samples in TCGA-HNSC was performed to obtain 1023 overlapping differentially expressed genes （DEGs） in TC and adjacent normal tissue （ANT） samples. Next, Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis was conducted to enrich the significant pathways of the 1023 DEGs and PI3K- Akt signaling pathway （P=0.011） was selected to be the candidate pathway. A total of 23 DEGs with ｜log2 fold change （FC）｜ ≥1.0 in phosphatidylinositol 3-kinase-serine/threonine kinase （PI3K-Akt） signaling pathway were subjected to survival analysis of 125 eligible TC samples in TCGA database, indicating increased integrin-α3 gene （ITGA3） expression was significantly associated with poorer prognosis. Taken together, our study suggested ITGA3 may facilitate the development of TC via activating PI3K-Akt signaling pathway.

ERK phosphorylation functions in invadopodia formation in tongue cancer cells in a novel silicate fibre-based 3D cell culture system

To screen for additional treatment targets against tongue cancer, we evaluated the contributions of extracellular signal-related kinase(ERK), AKT and ezrin in cancer development. Immunohistochemical staining showed that ERK and ezrin expressions were significantly higher in invasive squamous cell carcinoma than in carcinoma in situ. To investigate the roles of ERK and ezrin in cancer development, we used the non-woven silica fibre sheet Cellbedwith a structure resembling the loose connective tissue morphology in a novel 3 D culture system. We confirmed that the 3 D system using CellbedTMaccurately mimicked cancer cell morphology in vivo. Furthermore, cell projections were much more apparent in 3 D-cultured tongue cancer cell lines than in 2 D cultures. Typically, under conventional 2 D culture conditions, F-actin and cortactin are colocalized in the form of puncta within cells.However, in the 3 D-cultured cells, colocalization was mainly observed at the cell margins, including the projections. Projections containing F-actin and cortactin colocalization were predicted to be invadopodia. Although suppressing ezrin expression with small interfering RNA transfection caused no marked changes in morphology, cell projection formation was decreased, and the tumour thickness in vertical sections after 3 D culture was markedly decreased after suppressing ERK activity because both the invasion ability and proliferation were inhibited. An association between cortactin activation as well as ERK activity and invadopodia formation was detected. Our novel 3 D culture systems using Cellbed? are simple and useful for in vitro studies before conducting animal experiments. ERK contributes to tongue cancer development by increasing both cancer cell proliferation and migration via cortactin activation.

Co-registered photoacoustic and ultrasound imaging for tongue cancer detection

Tongue cancer is an increasingly common disease with high morbidity,Besides clinical obser-vation,biomedical imaging techniques have been investigated for early detection of tonguecancer.In this paper,we proposed a co-registered dual-modality photoacoustic(PA)and ul.trasound imaging technique to simultaneously map the functional and structural information ofhuman tongue,which has the potential to detect and diagnose tongue cancer in early stage,Theimaging probe comprises a 20-MHz side-view focused transducer for ultrasound imaging and PAdetection,a light path constructed by a multimode optical fiber,and a prism for PA illumination.Phantom experiments were conducted to evaluate the performance of the system includingpenetration depth,spatial resolution and signal-to-noise ratio.In vivo imaging of animaltumor and human tongue was carried out to show the feasibility of the proposed technique todetect tumor lesions in human tongue.The results of phantom and in vivo experiments suggestthat the proposed technique has the potential to detect the early-stage cancer lesions in humantongue.

Occult cervical lymph node metastases in 100 consecutive patients with cNO tongue cancer

Background Squamous cell carcinoma （SCC） of the tongue maxillofacial region. To provide clinical evidence for selective analyzing the characteristics and correlation of factors of occult with SCC of the tongue. is one of the most common cancers in the oral and neck dissection in management of cN0 patients by cervical lymph node metastases （OCLNM） in patients Methods From 2002 to 2006, 100 consecutive patients with SCC of the tongue were reviewed by analyzing the characteristics of OCLNM, diameter of the tumor, T classifications, depth of invasion, forms of growth, pathological grade and degree of differentiation. Results The rate of OCLNM in 100 patients with SCC of the tongue was 22%. The most common region with OCLNM was level Ⅱ in the ipsilateral neck, followed by levels Ⅰ and Ⅲ. There were 51.61% （16/31） of OCLNM in level Ⅱ and 87.10% （27/31） of OCLNM in levels Ⅰ-Ⅲ. There was no significant correlation between the diameter of tumor and OCLNM （P 〉0.05）. OCLNM was statistically significantly correlated with the depth of invasion, forms of growth, pathological grade and degree of differentiation （P 〈0.05）. The rate of occult metastases increased with the increased pathological grade, the decreased degree of differentiation and the increased depth of invasion. Conclusions The most common regions with OCLNM in cN0 patients with SCC of the tongue were levels Ⅰ-Ⅲ in the ipsilateral neck. Supraomohyoid neck dissection should be the elective treatment to the neck in patients with cN0 SCC of the tongue by consideration of the clinical and pathological factors for the depth of invasion, forms of growth, pathological grade, and degree of differentiation.

KIF18A is a potential prognostic factor and promotes tumor progression in oral tongue squamous cell carcinoma

The kinesin family member 18A protein was dysregulated in several human cancers and involved in cancer progression.However,the significance in oral tongue squamous cell carcinoma(OTSCC)has not been studied.The present study was intended to explore the functions of KIF18A in oral tongue squamous cell carcinoma.The immunohistochemistry(IHC)assay was performed to assess the relationships between the KIF18A protein expression level and clinical-pathological features of the patients.The biological functions of KIF18A in OTSCC cells were investigated by the experiments in vitro and in vivo.Based on immunohistochemistry,we found that KIF18A was correlated with the clinical-pathological features of OTSCC patients.High expression of KIF18A was associated with the lymph node metastasis,and clinical stages.In vitro experiments revealed that silencing of KIF18A significantly inhibited the expression of the proliferation and migration related proteins such as Ki67,proliferating cell nuclear antigen,matrix metalloproteinase-7 and matrix metalloproteinase-9,and thereby inhibiting the proliferation,migration and invasion of tumor cells.In vivo,knocking-down of KIF18A could inhibit the tumor growth in nude mice.In conclusion,we found KIF18A promoted tumor progression in vivo and in vitro and might become an effective target for the treatment of OTSCC.

Lingual lymph nodes:Anatomy,clinical considerations,and oncological significance

Lingual lymph nodes are an inconstant group of in-transit nodes,which are located on the route of lymph drainage from the tongue mucosa to the regional nodes in neck levels I and II.There is growing academic data on the metastatic spread of oral cancer,particularly regarding the spreading of oral tongue squamous cell carcinoma to lingual nodes.These nodes are not currently included in diagnostic and treatment protocols for oral tongue cancer.Combined information on surgical anatomy,clinical observations,means of detection,and prognostic value is presented.Anatomically obtained incidence of lingual nodes ranges from 8.6%to 30.2%.Incidence of lingual lymph node metastasis ranges from 1.3%to 17.1%.It is clear that lymph nodes that bear intervening tissues from the floor of the mouth should be removed to improve loco-regional control.Extended resection volume,which is required for the surgical treatment of lingual node metastasis,cannot be implied to every tongue cancer patient.As these lesions significantly influence prognosis,special efforts of their detection must be made.Reasonably,every tongue cancer patient must be investigated for the existence of lingual lymph node metastasis.Lymphographic tracing methods,which are currently implied for sentinel lymph node biopsies,may improve the detection of lingual lymph nodes.