Silencing ANLN hinders the proliferation, migration, invasion, and angiogenesis of oral squamous cell carcinoma.

BACKGROUND: The actin-binding protein anillin (ANLN) functions as an oncogene in various cancers but has not been fully studied in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression of ANLN in OSCC tissues and cell lines, to better understand its role in mediating proliferative, angiogenic, invasive, and metastatic capabilities in this type of cancer. METHODS: ANLN mRNA and protein levels were assessed using qPCR and western immunoblotting. The expression intensity of ANLN was evaluated using immunohistochemical (IHC) staining. Biological functional assays were employed to characterize the behavior of OSCC cells influenced by ANLN. Additionally, comprehensive bioinformatics analysis, including GO analysis and KEGG enrichment analysis, was performed on differentially expressed genes in ANLN-mediated pathways. RESULTS: OSCC tumors and cell lines exhibited higher ANLN expression. Silencing of ANLN significantly suppressed OSCC cell proliferation, as evidenced by a significant reduction in the Ki-67 index both in vitro and in vivo. The migration and invasive ability of OSCC cells were markedly diminished, coinciding with a decrease in epithelial-mesenchymal transition activity. ANLN was also found to promote angiogenic activity in OSCC cells, partly through synergistic effects mediated by vascular endothelial growth factor A (VEGFA). Downregulation of ANLN expression led to decreased VEGFA levels, resulting in reduced angiogenesis characterized by fewer vascular branches. CONCLUSIONS: Our findings highlight the promising role of ANLN as a biomarker for both diagnostic and prognostic in OSCC. Targeting ANLN with inhibitory strategies could impede the oncogenesis processes at the core of OSCC development, presenting significant opportunities for advancing therapeutic interventions.

Identification and Verification of a Prognostic Risk Signature in Oral Squamous Cell Carcinoma.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is a prevalent malignant condition. This study aimed to investigate the role of mTORC1 signaling and develop a prognostic model for OSCC. MATERIALS AND METHODS: The single-sample gene set enrichment analysis (ssGSEA) algorithm was utilized to calculate the Z-Score of Hallmarks in OSCC, followed by univariate Cox regression analysis to identify processes associated with prognosis. Weighted gene co-expression network analysis (WGCNA) was performed using transcriptomic data from the cancer genome atlas (TCGA) cohort to identify genes correlated with mTORC1 signaling. A six-gene prognostic model was constructed using multifactorial Cox regression analysis and validated using an external dataset. RESULTS: The study uncovered a strong linkage between mTORC1, glycolysis, hypoxia, and the prognosis of OSCC. mTORC1 signaling emerged as the most significant risk factor, negatively impacting patient survival. Additionally, a six-gene prognostic risk score model was developed which provided a quantitative measure of patients' survival probabilities. Interestingly, within the context of these findings, TP53 gene mutations were predominantly observed in the high-risk group, potentially underlining the genetic complexity of this patient subgroup. Additionally, differential immune cell infiltration and an integrated nomogram were also reported. CONCLUSION: This study highlights the importance of mTORC1 signaling in OSCC prognosis and presents a robust prognostic model for predicting patient outcomes.

Focusing on tumor and it's microenvironmental immune members for head and neck cancer patients.

OBJECTIVE: Immune-related gene expression levels in the tumor microenvironment (TM) of head and neck squamous cell carcinoma (HNSCC) patients was compared. MATERIALS AND METHODS: The CD163, CD274, CD86, FUT4, FOXP3, and ITGAX levels of HNSCC patients in their tumor tissues (n =76) and surrounding tissues adjacent to the tumor (n =76) were determined using quantitative real-time PCR (qRT-PCR). Changes in these genes were also evaluated by associating with demographical data of the patients. RESULTS: CD163, CD274, FUT4, and FOXP3 gene expression levels were significantly higher in tumor tissue than in surrounding tissue. FUT4 fold change was statistically higher in patients with lymph node involvement. CD86 expression was statistically lower in smokers of 50 boxes per year or more. CD163, CD274, and FUT4 expressions were increased in response to the presence of extranodal extension (ENE). CONCLUSIONS: These preliminary results demonstrate the alterations in expression levels of immunologic markers are associated with the clinical presentations of HNSCC. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Integrating Mcm-2 and Ki-67 Immunohistochemistry with Clinico-Pathologic Parameters for Enhanced Prognostic Accuracy in Oral Verrucous Lesions.

BACKGROUND: Oral verrucous lesions (OVLs) present a diagnostic challenge due to their diverse and often confusing histopathological features. Accurate differentiation is essential for improving diagnosis and predicting prognosis. In addition to assessing overall survival (OS) and disease-free survival (DFS) in verrucous squamous cell carcinoma (VSCC) and conventional OSCC, this study seeks to evaluate the expression of Mcm-2 and Ki-67 in verrucous lesions and oral squamous cell carcinoma (OSCC). These findings will be correlated with the nuclear expression of Mcm-2 and Ki-67. METHODOLOGY: Ninety tissue samples that were paraffin embedded and formalin-fixed were examined using immunohistochemistry to determine the expression of Mcm-2 and Ki-67. Data on survival and clinico-pathologic characteristics were taken from patient records. Statistical analyses were conducted using Independent T-tests, Cox regression models, and Kaplan-Meier survival analysis. RESULTS: Mcm-2 was identified as a more sensitive and prognostic marker compared to Ki-67 across the study groups. Mcm-2 overexpression was observed in all cases of verrucous hyperplasia with dysplasia, verrucous carcinoma (VC), VSCC, and conventional OSCC. The 3-year OS and DFS rates were lower in conventional OSCC (75% and 64.3%, respectively) compared to VSCC (90% and 70%). CONCLUSION: This study represents the first initiative to employ both Mcm-2 and Ki-67 as proliferative markers for distinguishing between various oral verrucous lesions. Mcm-2 proves to be a valuable marker for differentiating between potentially malignant and malignant verrucous lesions. However, further validation with larger sample sizes and longer follow-up periods is necessary to confirm its role in predicting OS and DFS.

Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization.

BACKGROUND: Precancerous and malignant tumours arise within the oral cavity from a predisposed "field" of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as "Field Cancerization". The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients. METHODS: We have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites - one each from buccal anterior and posterior alveolus, dorsum of tongue-mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization. RESULTS: A missense CASP8 gene mutation (p.S375F) was observed to be the initiating event in oral tumour field development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability. CONCLUSION: CASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.

Evaluation of the Prevalence and Potential Impact of HPV Vaccines in Patients with and Without Oral Diseases: A Ten-Year Retrospective Study.

BACKGROUND: The prevalence of oral human papillomavirus (HPV) in the healthy population and patients with oral diseases such as oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and oral benign lesions (BL), is not consistently described in the literature, with scarce and often heterogeneous data. In addition, the efficacy of HPV prophylactic vaccines in preventing HPV-related oral disorders has been scarcely investigated. METHODS: The prevalence of HPV and the potential impact of vaccines were analyzed in 1,415 oral rinse specimens, collected over 10 years and grouped into four categories based on histological/clinical diagnosis. RESULTS: HPV prevalence in OSCC, OPMD, and BL patients and in healthy individuals potentially exposed to HPV (HPE) was comparable (12.7 vs. 27.2% vs. 13.5 vs. 9%). Statistical analysis of the vaccine impact involved calculating high and low estimates and showed a significant difference only for the low effect. The nonavalent vaccine had higher low estimates than the bivalent vaccine in OSCC and HPE patients (29.6 vs. 51.9%, p < 0.05; 18.2 vs. 42.4%, p < 0.05), while for OPMD and BL, the frequency of bivalent low estimates was lower than that of quadrivalent and nonavalent (48.6 vs. 68.6%, p < 0.05 and 48.6 vs. 77.1%, p < 0.05; 23.9 vs. 50.7%, p < 0.05, and 23.9 vs. 63.4%, p < 0.05). CONCLUSIONS: This study provided new insights into the prevalence of oral HPV and showed that the nonavalent vaccine may provide better protection than the other vaccines in the presence of an OSCC diagnosis. Conversely, the quadrivalent vaccine may be sufficient to prevent OPMD and BL.

Precise Identification of Oral Cancer Lesions Using Artificial Intelligence.

Dentists, especially those who are not oral lesion specialists and live in rural areas, need an artificial intelligence (AI) system for accurately assisting them in screening for oral cancer that may appear in smartphone images. Not many literatures present a viable model that addresses the needs, especially in the context of oral lesion segmentation in smartphone images. This study demonstrates the use of a deep learning-based AI for simultaneously identifying types of oral cancer lesions as well as precisely outlining the boundary of the lesions in the images for the first time. The lesions of interest were oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) lesions. The model could successfully (1) detect if the images contained the oral lesions, (2) determine types of the lesions, and (3) precisely outline the boundary of the lesions. With future success of our project, patients will be diagnosed and treated early before the pre-cancer lesions can progress into deadly cancerous ones.

LncRNA NR2F2-AS1 inhibits the progression of oral squamous cell carcinoma by mediating the miR-32-5p/SEMA3A axis.

Previous studies have supported a tumor-suppressive role of semaphorin 3A (SEMA3A) in several tumors including oral squamous cell carcinoma (OSCC). However, in-depth characterization of the role of SEMA3A in OSCC and the underlying molecular mechanisms is lacking. Gene and protein expressions were detected using quantitative real-time PCR, western blot assay, and immunohistochemistry. OSCC cell metastasis was evaluated using Transwell and angiogenesis of human umbilical vein endothelial cells (HUVECs) was determined using tube formation assay. The interactions among molecules were predicted using bioinformatics analysis and validated using luciferase activity experiment and RNA immunoprecipitation assay. Pulmonary metastasis was evaluated using hematoxylin and eosin staining after constructing a lung metastasis tumor model in mice. SEMA3A expression was decreased in OSCC cells and its overexpression led to suppression of epithelial-mesenchymal transition (EMT), migration, and invasion of OSCC cells and angiogenesis of HUVECs. miR-32-5p was identified as an upstream molecule of SEMA3A and long non-coding RNA NR2F2 antisense RNA 1 (NR2F2-AS1) was validated as an upstream gene of miR-32-5p. Further experiments revealed that the inhibitory effects of NR2F2-AS1 overexpression on EMT, migration, invasion of OSCC cells, and angiogenesis of HUVECs as well as tumor growth and metastasis in mice were mediated via the miR-32-5p/SEMA3A axis. To conclude, NR2F2-AS1 may attenuate OSCC cell metastasis and angiogenesis of HUVECs and suppress tumor growth and metastasis in mice via the miR-32-5p/SEMA3A axis.

XPO1 serves as a prognostic marker involving AKT/MAPK/TGFBR1 pathway in OSCC.

BACKGROUND: Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. METHODS: The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. RESULTS: XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. CONCLUSIONS: XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1.

Expression analysis of SOX2 and SOX9 in patients with oral squamous cell carcinoma.

BACKGROUND: Lately SOX2 and SOX9, transcription factors associated with stemness-like phenotypes of cancer cells, have been linked to tumor growth, metastasis, and resistance to therapy. METHODS: This study aimed on evaluating the expression of SOX2 and SOX9 in a large cohort of patients with OSCC including primary and recurrent tumors and corresponding lymph node metastases. Semiautomatic digital pathology scoring was used to determine protein expression and survival analysis was performed to evaluate its prognostic significance. RESULTS: We found a significant downregulation of SOX9 from primary disease to lymph node metastases (p < 0.001). SOX9 expression and the subgroup SOX2lowSOX9high were significantly correlated with worse overall survival (p < 0.05). Additionally, SOX2lowSOX9high expression pattern was confirmed as independent prognosticator for overall survival. CONCLUSIONS: These results indicate the relevant role of SOX2 and SOX9 in patients with OSCC and show the clinical relevance for further investigation on the molecular mechanisms underlying SOX-related gene expression.

Evaluation pattern within tumor microenvironment and consequent gene expression in oral cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the head and neck squamous cell cancer group. The increasing frequency of oral carcinomas and their late-stage appearance is a major worldwide health concern. MicroRNAs (miRNAs) appear to play an important role in cancer growth and progression, according to growing data, whereas no information is available regarding miR-7113-3p and miR-6721-5p involvement in OSCC. In this article, the expression of MAP2K1, miR-7113-3p, and miR-6721-5p was examined for possible bio-logical functions in the advancement of oral squamous cell carcinoma. MATERIAL AND METHODS: We used quantitative real-time PCR (to examine the mRNA expression of MAP2K1, miR-7113-3p, and miR-6721-5p in fresh frozen OSCC tissues and adjacent normal fresh frozen tissues from 30 patients, and we investigated their relationship with clinical parameters. RESULTS: MAP2K1 expression was found to be dramatically increased in tumor tissues than in normal tissues, whereas miR7113-3p and miR-6721-5p expression was significantly decreased. Furthermore, a statistical correlation of P = 0.04 was also observed between increased MAP2K1 expression and perineural invasion. Additionally, we noted that the downregulation of miR-7113-3p appears to correlate positively with overexpression of MAP2K1 (P = 0.0218), and a negative correlation was observed between downregulation of miR-6721-5p and overexpression of MAP2K1 (P = 0.7771). CONCLUSION: Based on these findings, miR-7113-3p and miR-6721-5p might be prospective bio-markers for OSCC patients, and could be utilized to detect OSCC at an early stage for future dia-gnosis. MAP2K1 overexpression has been linked to the development of OSCC and perineural invasion.

Recent advances in minimally invasive biomarkers of OSCC: from generalized to personalized approach.

Oral cancer is the 6th most common type of cancer worldwide, and oral squamous cell carcinoma (OSCC) accounts for >90% of oral cancers. It is a major health problem, particularly in low- and middle-income countries (LMICs), due to both its high incidence and significant mortality and morbidity. Despite being a global burden, and even with the significant advancement in the management of OSCC, the overall outcome of the disease is still abysmal. With the advent of time, advanced diagnostic and treatment approaches have come into practice, but the burden of the disease has not improved significantly. Major reasons attributed to the poor outcome are delay in diagnosis, locoregional recurrence and resistance to the currently available treatment regimen. In this review, we have highlighted the existing challenges in the diagnosis and have emphasized the advancements in minimally invasive biomarkers. Additionally, the importance of collaborative multidimensional approaches involving clinicians and researchers has been discussed, as well as the need to redefine and establish better utility and management of existing diagnostic and treatment protocols along with the minimally invasive/non-invasive biomarkers.

Deciphering the role of TLR3 polymorphisms in oral squamous cell carcinoma pathogenesis: A case-control study.

Background: Oral squamous cell carcinoma (OSCC) poses a significant global health burden, particularly prevalent in regions like India. Despite advancements in diagnostics, early detection of OSCC remains challenging, necessitating novel diagnostic modalities. Toll-like receptors (TLRs) and their polymorphisms have emerged as potential contributors to OSCC pathogenesis. Methods: This retrospective case-control study examined 120 individuals, including 60 OSCC cases and 60 healthy controls. Genotyping of TLR3 single-nucleotide polymorphisms (SNPs) rs3775290 and rs3775291 was conducted using TaqMan allelic discrimination real-time polymerase chain reaction. Functional consequence analysis and TLR3 expression profiling were performed to elucidate their role in OSCC pathogenesis. Results: Significant associations were observed between TLR3 SNPs and OSCC susceptibility, particularly at loci rs3775290 and rs3775291. Functional consequence analysis revealed pathogenic mutations in TLR3 genes, potentially affecting protein structure and function. TLR3 overexpression was detected in OSCC lesions, implicating its involvement in disease progression. Conclusion: TLR3 polymorphisms play a pivotal role in OSCC pathogenesis, offering potential biomarkers for diagnosis and prognosis. Targeting TLR3-mediated pathways may hold promise in personalised OSCC management. Further research is warranted to elucidate the precise mechanisms underlying TLR3-mediated carcinogenesis in OSCC, facilitating the development of tailored therapeutic strategies.

Oral squamous cell carcinoma: A 26 years institutional cross-sectional study.

Context: The variance in the prevalence of oral squamous cell carcinoma (OSCC) around the world has been associated with a number of sociocultural traits, significant regional variations in risk factors, variations in data gathering, and the degree of health service development in different populations. Here, we undertake a 26 years institutional review and analysis of OSCC cases. Aim: To evaluate and analyse 26 years Institutional Data of OSCC. Settings and Design: Department of Oral and Maxillofacial Pathology's archives, Government Dental College and Hospital, Nagpur, Maharashtra, and observational cross-sectional study. Methods and Material: This study examines instances of OSCC that were histologically diagnosed between 1997 and 2022. All information pertaining to cases of OSCC was obtained from the departmental archives. Statistical Analysis Used: Data tabulated and then subjected to descriptive statistical analysis with the SPSS statistical software. Results: The total number of the patients included 1508 (69.6%) males and 660 (30.4%) females, whose age ranged from the second decade to the tenth decade of life with a mean age of 55.5 years with a range of 20-91 years. The incidence was the highest in the fifth and sixth decades (n = 603, 27.8% and n = 572, 26.4%), respectively. The left buccal mucosa recorded the maximum number of cases (left buccal mucosa 559, 25.8%). There were 1405 (64.8%) cases of well-differentiated SCC, 301 (13.9%) cases of moderately differentiated SCC, and 51 (2.4%) cases of poorly differentiated SCC. Conclusions: The overall incidence and prevalence of OSCC can be estimated using baseline epidemiological data from our institution.

Risk stratification of submandibular salivary gland involvement in oral squamous cell carcinoma based on histopathological parameters: A 15-year retrospective study.

Objective: Squamous cell carcinoma (SCC) represents about 90% of all oral malignancies. The study aimed to assess the involvement of the submandibular salivary gland (SMG) in oral SCC (OSCC) patients and the need for SMG excision. Materials and Methods: Demographics, clinical information and staging of the 210 patients undergoing surgery for OSCC were obtained from the department records. The histopathological slides were retrospectively reviewed. The nodal status was also verified with the histopathology reports. Frequency distribution, Chi-square association, ordinal logistic regression analysis and Kaplan-Meier analysis were performed. Results: SMG was excised in 171 patients. Five patients had SMG involvement. Buccal mucosa (BM) and gingivobuccal sulcus had a greater risk of level IB metastases (P < 0.01). Pattern 3 and pattern 4 of invasion had a higher risk of level IB metastases (P = 0.04). Depth of invasion (DOI) >4 mm was associated with level IB lymph node (LN) involvement (P = 0.0001). DOI >4 mm to 8 mm had 3.7 times the risk and a DOI >8 mm to 12 mm had 5 times the risk of level IB metastases. Pattern of invasion (POI), tumour budding and DOI >4 mm were significant prognosticators for patient survival. Conclusion: Histologically, patients may be categorised as 'high risk': those with an increased risk of level IB LN involvement and 'low risk': those at low risk for level IB involvement with the help of POI, tumour budding and DOI as risk factors. In low-risk patients, SMG may be spared and the level IB LNs are dissected. High-risk patients may be chosen as candidates for SMG transfer or excision based on the extent of LN involvement.

Comprehensive insights into oral squamous cell carcinoma: Diagnosis, pathogenesis, and therapeutic advances.

Oral squamous cell carcinoma (OSCC) is considered the most common type of head and neck squamous cell carcinoma (HNSCC) as it holds 90 % of HNSCC cases that arise from multiple locations in the oral cavity. The last three decades witnessed little progress in the diagnosis and treatment of OSCC the aggressive tumor. However, in-depth knowledge about OSCC's pathogenesis, staging & grading, hallmarks, and causative factors is a prime requirement in advanced diagnosis and treatment for OSCC patients. Therefore present review was intended to comprehend the OSCCs' prevalence, staging & grading, molecular pathogenesis including premalignant stages, various hallmarks, etiology, diagnostic methods, treatment (including FDA-approved drugs with the mechanism of action and side effects), and theranostic agents. The current review updates that for a better understanding of OSCC progress tumor-promoting inflammation, sustained proliferative signaling, and growth-suppressive signals/apoptosis capacity evasion are the three most important hallmarks to be considered. This review suggests that among all the etiology factors the consumption of tobacco is the major contributor to the high incidence rate of OSCC. In OSCC diagnosis biopsy is considered the gold standard, however, toluidine blue staining is the easiest and non-invasive method with high accuracy. Although there are various therapeutic agents available for cancer treatment, however, a few only are approved by the FDA specifically for OSCC treatment. The present review recommends that among all available OSCC treatments, the antibody-based CAR-NK is a promising therapeutic approach for future cancer treatment. Presently review also suggests that theranostics have boosted the advancement of cancer diagnosis and treatment, however, additional work is required to refine the role of theranostics in combination with different modalities in cancer treatment.

Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy.

Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.

The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. METHODS: 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. RESULTS: This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK. CONCLUSIONS: This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.

Effects of Angiogenic Factors on the Epithelial-to-Mesenchymal Transition and Their Impact on the Onset and Progression of Oral Squamous Cell Carcinoma: An Overview.

High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels' formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy.

Interpretation of Epidermal Growth Factor Receptor Status in Microscopic Tumor-Free Surgical Margins and Lymph Nodes in Patients with Oral Squamous Cell Carcinoma: An Analysis of 125 Margins.

Background: Squamous cell carcinomas are the most common type of oral cancer contributing for around 90%. The overall survival is below 50% for these patients. There is a requirement for a non-invasive marker to predict the prognosis. The epidermal growth factor (EGF) and their receptors (EGFR, ErbB-1) are not only documented to play a critical and an influential role in cell growth and differentiation in normal/healthy tissues, but may also plays an important role in malignant disease progression and tumorigenesis. Objective: This study was done to find the significance of EGF receptor expression on microscopic free tumour margins and lymph nodal margins to predict the survival of the patient in a 2-year follow-up. Materials and Methods: A prospective cohort study of 25 patients was performed in biopsy proven oral squamous cell carcinoma patients who reported to our department from July 2017 to June 2019. The data were collected from their histopathological report, they were- pTNM staging, surgical margins (superior and inferior, anterior, posterior), nodal status and scoring of EGFR expression on wax blocks was done. Total of 125 wax blocks were analysed for the study. Follow-up of 2 years were recorded in the study to evaluate the survival of the patients. Result: The expression of EGFR on microscopic tumour-free surgical margins and lymph nodes was p value 0.023 which was statistically significant. The level of significance between EGFR and status of patients after 2-year follow-up was having p value 0.031. Out of 25 patients, 5 patients were dead at a 2-year follow-up. Out of these 5 patients who were dead, 3 patients had a local recurrence and 2 patients had distant metastasis. Conclusion: This cohort study concludes that EGFR is an important prognostic marker and must be analysed in all microscopic tumour-free margins and lymph nodes in advanced oral squamous cell carcinomas to predict the local recurrences affecting the survival of the patients and the need for addition of anti-EGFR agents in adjuvant treatment. Since the sample size is small, large scale studied must be done to validate the need for adding anti-EGFR agents in adjuvant treatment to improve the survival of patients.