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Objectives The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. Methods Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro. The immunological differences underlying iCIKs transfer were investigated through phenotype, cytokine secretion and PD-1/PD-L1 inhibition analysis. Results The serum PD-L1 levels were elevated in the TSCC patients. PD-L1 was detected on both human TSCC cells and tumour tissue sections. PD-1 expression was much higher on the PBMCs of TSCC patients than on in vitro cultured iCIKs. Interruption of PD-1/PD-L1 interaction enhanced the cytotoxicity of iCIKs in vitro. CD3 + CD8+ T cell proportion and cytokine IL-6 secretion decreased after chemotherapy. The infusion of iCIKs effectively reversed the immunosuppression through the upregulation of the CD3 + CD8+ T cell proportion and Th cell cytokine secretion (IFN-γ, TNF-α, IL-4 and IL-6). Twelve responders are currently alive (95.7+ months), another patient 83 months. Conclusion Our findings indicated that the PD-1/PD-L1 interaction contributes to the immunosuppression in TSCC patients. ICIKs transfer is an effective therapy to reverse the immunosuppression caused by surgical procedures and chemotherapy and improve immune system function. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critically involved in cancer metastasis. We found an elevation of FAK expression in highly metastatic melanoma B16F10 cells compared with its less metastatic partner B16F1 cells. Down-regulation of the FAK expression by either small interfering RNA or dominant negative FAK (FAK Related Non-Kinase, FRNK) inhibited the B16F10 cell migration in vitro and invasiveness in vivo. The mechanism by which FAK activity is up-regulated in highly metastatic cells remains unclear. In this study, we reported for the first time that one of the Est family proteins, PEA3, is able to transactivate FAK expression through binding to the promoter region of FAK. We identified a PEA3-binding site between nucleotides −170 and +43 in the FAK promoter that was critical for the responsiveness to PEA3. A stronger affinity of PEA3 to this region contributed to the elevation of FAK expression in B16F10 cells. Both in vitro and in vivo knockdown of PEA3 gene successfully mimicked the cell migration and invasiveness as that induced by FAK down-regulation. The activation of the well-known upstream of PEA3, such as epidermal growth factor, JNK, and ERK can also induce FAK expression. Furthermore, in the metastatic human clinic tumor specimens from the patients with human primary oral squamous cell carcinoma, we observed a strong positive correlation among PEA3, FAK, and carcinoma metastasis. Taking together, we hypothesized that PEA3 might play an essential role in the activation of the FAK gene during tumor metastasis. [ABSTRACT FROM AUTHOR]

Objective: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. Subjects and Methods: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography–mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. Results: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. Conclusions: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC. [ABSTRACT FROM AUTHOR]

Aims: Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological characteristics, and the individual histological characteristics of the tumors are poorly understood. Therefore, calculating the proportion of tumor cells in different regions that allow assessment of the prognostic outcomes for OSCC patients would be of great clinical significance. Methods and Results: We established an open‐source software‐based analytic pipeline that defines the inner tumor and invasive tumor front (ITF) in pancytokeratin‐stained whole slide images (WSIs) and quantifies the tumor‐stroma ratio (TSR) within the two regions. We applied this method to 114 patients with OSCC and predicted patient prognosis by the TSR. The proportion of tumor area in the inner tumor was generally higher than that in the ITF (p < 0.0001). TSR was an independent prognostic factor for overall survival (OS) (p = 0.016), disease‐free survival (DFS) (p = 0.026), and relapse‐free survival (RFS) (p = 0.037) in inner tumor, and TSR was an independent prognostic factor for OS (p = 0.00052), DFS (p = 0.035), and metastasis‐free survival (MFS) (p = 0.038) in the ITF. Tumor‐low status was associated with poorer prognosis. There was a significant correlation between the TSR and perineural invasion (PNI) in the inner tumor (p = 0.009). Conclusions: The histopathological characteristics of different regions of OSCC may be used to develop the potential prognostic markers. The TSR of the inner tumor is more targeted in predicting prognosis and accurately assesses the risk of PNI+. [ABSTRACT FROM AUTHOR]

Introduction: Metabolite stability is critical for tissue metabolomics. However, changes in metabolites in tissues over time from the operating room to the laboratory remain underexplored. Objectives: In this study, we evaluated the effect of postoperative freezing delay time on the stability of metabolites in normal and oral squamous cell carcinoma (OSCC) tissues. Methods: Tumor and paired normal tissues from five OSCC patients were collected after surgical resection, and samples was sequentially quenched in liquid nitrogen at 30, 40, 50, 60, 70, 80, 90 and 120 min (80 samples). Untargeted metabolic analysis by liquid chromatography–mass spectrometry/mass spectrometry in positive and negative ion modes was used to identify metabolic changes associated with delayed freezing time. The trends of metabolite changes at 30–120 and 30–60 min of delayed freezing were analyzed. Results: 190 metabolites in 36 chemical classes were detected. After delayed freezing for 120 min, approximately 20% of the metabolites changed significantly in normal and tumor tissues, and differences in the metabolites were found in normal and tumor tissues. After a delay of 60 min, 29 metabolites had changed significantly in normal tissues, and 84 metabolites had changed significantly in tumor tissues. In addition, we constructed three tissue freezing schemes based on the observed variation trends in the metabolites. Conclusion: Delayed freezing of tissue samples has a certain impact on the stability of metabolites. For metabolites with significant changes, we suggest that the freezing time of tissues be reasonably selected according to the freezing schemes and the actual clinical situation. [ABSTRACT FROM AUTHOR]

Background: Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that catalyzes the methylation of nicotinamide (NAM) to generate 1-methyl nicotinamide (MNAM). Although previous studies have shown that NNMT is frequently dysregulated to promote the onset and progression of many malignancies, its expression profile, prognostic value and function in oral squamous cell carcinoma (OSCC) are still unknown. Methods: We used untargeted metabolomics based on mass spectrometry to analyze potential metabolite differences between tumors and matched adjacent normal tissues in 40 OSCC patients. Immunohistochemistry (IHC) was used to analyze the NNMT expression profile in OSCC, and the diagnostic and prognostic values of NNMT were evaluated. Next, qPCR and Western blot were used to compare the expression of NNMT in five OSCC cell lines. Stable transfected cell lines were constructed, and functional experiments were carried out to elucidate the effects of NNMT on the proliferation and migration of OSCC cells. Finally, gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data to investigate the potential functional mechanisms of NNMT in OSCC. Results: We found that the nicotinamide metabolic pathway was abnormally activated in OSCC tumor tissues compared with normal tissues. NNMT was expressed ubiquitously in tumor cells (TCs) and fibroblast-like cells (FLCs) but was absent in tumor-infiltrating lymphocytes (TILs). OSCC patients with highly expressed NNMT in TCs had higher risk of lymph node metastasis and showed a worse pattern of invasion (POI). Moreover, patients with highly expressed NNMT were also susceptible to postoperative recurrence. Highly expressed NNMT can independently predict shorter disease-free survival and recurrence-free survival. Functionally, we demonstrated that the ectopic expression of NNMT promoted OSCC tumor cell proliferation and migration in vitro. Conversely, silencing exerted significantly opposite effects in vitro. In addition, GSEA showed that highly expressed NNMT was mainly enriched in the epithelial–mesenchymal transformation (EMT) pathway, which displayed a significant positive correlation with the six classic EMT markers. Conclusions: Our study uncovered that NNMT may be a critical regulator of EMT in OSCC and may serve as a prognostic biomarker for OSCC patients. These findings might provide novel insights for future research in NNMT-targeted OSCC metastasis and recurrence therapy. [ABSTRACT FROM AUTHOR]

Background: This study was performed to examine whether lipopolysaccharide can influence cell migration and epithelial-mesenchymal transition of oral squamous cell carcinoma.Methods: Three oral squamous cell carcinoma cell lines (HSC3, CAL27, and SCC4) were obtained for the study. TLR4 expression in three cell lines was analyzed by Q-PCR and Western blot. After cells treated with LPS, cell migration was analyzed by wound-healing and chemotaxis cell migration assay. Changes of E-cadherin and vimentin expression were tested by Western blot and immunofluorescence staining. To examine NF-κB activation, NF-κB nuclear translocation was investigated.Results: TLR4 was expressed in all three cell lines and was highest in HSC3 while lowest in SCC4. TLR4 ligand lipopolysaccharide accelerated wound healing and enhanced cell migration. Also, it stimulated epithelial-mesenchymal transition demonstrated by decreased E-cadherin and increased vimentin expression. Lipopolysaccharide also provoked NF-κB nuclear translocation. Either TLR4 or NF-κB blocking reverted these effects.Conclusions: Lipopolysaccharide can induce TLR4-mediated epithelial-mesenchymal transition and cell migration in oral squamous cell carcinoma. These responses could further affect tumor progressing by inducing tumor cell metastasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: p16 has often been found to be overexpressed in patients oral squamous cell carcinoma (OSCC), but its prognostic value between anatomic subsites is still unclear. OBJECTIVE: The aim of this study was to investigate the diagnostic and prognostic values of p16 in OSCC originating from tongue, gingiva or buccal mucosa. METHODS: A total of 147 OSCC patients with tumors arising from the tongue, gingiva or buccal mucosa were enrolled in this study. p16 expression was detected using immunohistochemistry (IHC), and the presence of HPV16 was determined by real-time PCR in p16 positive patients. The correlation of p16 expression with the clinical parameters was evaluated. RESULTS: Only one p16 positive patient with a cut off value of 25% and 75% was HPV16 positive. Although overall survival (OS), recurrence free survival (RFS) and metastasis free survival (MFS) had no significant differences between the p16 positive and negative patients, p16 negative patients (cut off value 25%) had more RFS in the buccal mucosa cancer (p = 0.03) than the p16-positive patients. CONCLUSIONS: The prevalence of HPV16 in Chinese OSCC patients was low. p16 overexpression decoupled from HPV infection was not a prognostic marker for OSCC patients except for patients with the buccal mucosa cancer. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-β (TGF-β) exerts its versatile function (oncogenic or tumor suppressive role) during the carcinogenesis in tumor microenvironment-dependent manner. Considering the tumor heterogeneity, spatial and temporal distribution of TGF-β in oral squamous cell carcinoma (OSCC) remained to be elucidated.Methods: Formalin-fixed, paraffin-embedded sections derived from 73 patients with OSCC were immunostained, revealing expression patterns of TGF-β, both at the regions of tumor center (TC) and invasive tumor front (ITF).Results: The TGF-β levels on tumor cells, fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs) were comparable and showed to be cell-type-independent manner. Although TC regions harbored less positive staining of TGF-β than ITF in tumor cells (TGF-βTumor cell ) (89.0% vs 98.3%; P = 0.037), FLCs (TGF-βFLC ) (86.3% vs 96.6%; P = 0.043), and TILs (TGF-βTIL ) (83.6% vs 94.8%; P = 0.044), respectively, TGF-β at TC regions, not at ITF, correlated to poor clinical outcomes. At TC regions, patients with high TGF-βTumor cell had high recurrence rate, and patients with high TGF-βTIL showed inferior worst pattern of invasion. Of note, high TGF-βTumor cell at TC predicted shorter overall survival time, recurrence-free survival, and disease-free survival in patients with OSCC, whereas high TGF-βTIL had no association with survival time. Cox regression analyses indicated that tumor cell-derived TGF-β at TC was an independent risk factor for survival outcome in patients with OSCC.Conclusions: Tumor cell-derived TGF-β at TC regions, but not at ITF, could be a promising predictor for disease recurrence and poor prognosis of patients with OSCC. [ABSTRACT FROM AUTHOR]

As a nuclear and nucleolar protein, proliferation marker protein Ki-67 (Ki-67) serves a vital role in tumorigenesis due to its positive correlation with tumor proliferation. High expression of Ki-67 in the cell cycle from the G1 to M phase makes it a potential biomarker for certain tumors and useful for selecting medical treatment. However, the diagnostic value of Ki-67 in oral squamous cell carcinoma (OSCC) has not been fully evaluated. In the present study, the objective was the elucidation of the prognostic value of Ki-67 in a large number of OSCC patients. Ki-67 expression was detected by immunohistochemical staining methods in 298 OSCC specimens and 98 tumor-free oral mucosa specimens (62 dysplasia mucosa and 36 normal mucosa), acquired from Nanjing Stomatological Hospital, Medical School of Nanjing University (Nanjing, China). Expression of Ki-67 in normal tissues, dysplasia tissues and OSCC tissues was compared. Associations between Ki-67 expression and clinicopathological parameters were analyzed by χ2 test. Kaplan-Meier survival curves and Cox progression analysis were used to assess the diagnostic value of Ki-67 for OSCC. The results showed that Ki-67 expression was higher in OSCC tissues than in tumor-free tissues and that it increased with the progression of dysplasia in oral mucosa tissues. In addition, patients with high Ki-67 expression had a worse clinical outcome, including poor tumor differentiation (P=0.001), increased positive lymph node metastasis (P=0.006) and increased worst pattern of invasion type (P<0.0001). Kaplan-Meier survival analysis demonstrated that higher Ki-67 expression was associated with poorer overall survival (OS) (P=0.035), recurrence-free survival (RFS) (P=0.017), metastasis-free survival (MFS) (P=0.032) and disease-free survival (DFS) (P=0.018) times. Additional multivariate analysis demonstrated that Ki-67 expression was negatively associated with OS, DFS, RFS and MFS. In conclusion, Ki-67 overexpression is associated with the progression of OSCC and serves as an independent prognostic factor for OSCC patients. [ABSTRACT FROM AUTHOR]

Background: Monocytes, which subdivided into three functional subsets (classical, intermediate, and nonclassical), play important roles in the progression of cancer. The subset composition is altered in several pathologic conditions including cancers. However, the composition and function of circulating monocyte subsets in patients with oral squamous cell carcinoma (OSCC) are still obscure. Methods: The frequencies of monocyte subsets in peripheral blood of patients with OSCC and healthy donors are determined by flow cytometry, and their diagnostic values for OSCC were evaluated. The associations between levels of monocyte subsets and clinicopathological features of patients with OSCC were analyzed using cross‐tabulation with the chi‐square test. Results: We demonstrated that the frequency of CD14++CD16+ intermediate monocytes was remarkably increased (P < 0.0001) in OSCC patients compared with healthy controls (7.33% ± 2.56% of total monocytes, n = 68 versus 4.78% ± 1.50% of total monocytes, n = 57). A trend of decrease in CD14++CD16− classical subset was observed between these two groups (P = 0.0508), whereas no significant difference was detected in CD14+CD16++ nonclassical subset (P > 0.05). The receiver operating characteristic (ROC) curve analysis indicated that the frequency of intermediate monocytes (AUC = 0.810, P < 0.0001) could be a potential diagnostic biomarker to discriminate patients with OSCC from healthy subjects. Moreover, this parameter was significantly correlated to the worst pattern of invasion (WPOI, P < 0.05) of OSCC tissues. Conclusions: Detection of monocyte subsets in peripheral blood sheds a light on utilizing the frequency of intermediate monocytes as a potential diagnostic biomarker for OSCC. [ABSTRACT FROM AUTHOR]

The status of lymph node (LN) metastasis, including the number and location of positive LNs, is a significant prognostic factor for oral squamous cell carcinoma (OSCC). Therefore, knowing the number and location of positive LNs is essential for prognosis. However, surgeons often have difficulty locating LNs. In the present study a practical device to improve the location of LNs in neck resection specimens was intoduced: the optical lymph nodes detection system (OLNDS). With the assistance of the OLNDS LNs were easier to locate and a significantly higher number of LNs were identified (P=0.006). The false detection rate was also significantly reduced compared with the traditional method (P=0.0034). The OLNDS was observed to be a valuable adjunct to the traditional method and may be useful for studying the value of LN metastasis in OSCC prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Margin status and invasion pattern are prognostic factors for oral tongue squamous cell carcinoma (OTSCC). Current methods to identify these factors are limited to 2D observation; it is necessary to explore 3D reconstruction with whole-mount sample to improve the accuracy of analysis. This study aimed to study the tissue preparation, section generation, and 3D reconstruction with whole-mount OTSCC specimen.Study Design: Two OTSCC samples were retrieved from Nanjing Stomatological Hospital, Medical School of Nanjing University. One sample was sliced into 3 equal-sized pieces and subjected to different processing schedules to determine the best method. The second sample was processed accordingly. Serial whole-mount sections of the second sample were generated, stained with HE/anticytokine antibody in intersection manner, and scanned into digital images. Digital images were aligned and reconstructed into 3D images with Hetero Genius Medical Image Manager 3D Pathology Add-On [HGMIM3D].Results: Successful serial whole-mount sections of comparable quality to traditional sections were generated. Three-dimensional images with serial whole-mount sections were successfully generated.Conclusions: Whole-mount histopathological 3D reconstruction of OTSCC was successfully generated, providing a solid foundation for comprehensive margin and invasion analysis. Although future study and improvement were needed, whole-mount histopathological 3D reconstruction proved to be a promising method in OTSCC study. [ABSTRACT FROM AUTHOR]

Aims Toll-like receptor ( TLR)-7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR-7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR-7 in oral squamous cell carcinoma ( OSCC) are unclear. Methods and results Twenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR-7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR-7 in tumour cells ( TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR-7 in stroma fibroblast-like cells ( FLCs) had low tumour stage, no lymph node metastasis ( LNM) and better prognosis. Furthermore, Ki-67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)+ tumour-infiltrated lymphocytes were assessed and we found that TLR-7high TCs were infiltrated by fewer CD3+ CD4+ but more FoxP3+ lymphocytes. Importantly, patients with TLR-7low TCs and TLR-7high FLCs had less FoxP3+ lymphocyte infiltration and longer survival time than those with TLR-7high TCs/ TLR-7low FLCs, although TLR-7 was not an independent prognostic factor for OSCC. Conclusions The low expression of TLR-7 in tumour and high expression of TLR-7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR-7 agonist. [ABSTRACT FROM AUTHOR]

Background: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. Materials: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients' tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. Results: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial–mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. Conclusions: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy. [ABSTRACT FROM AUTHOR]

Background: Local resident normal fibroblasts (NFs) are the major source of cancer-associated fibroblasts (CAFs), which are distinguishable from NFs by their tumor-supportive properties. However, the mechanism and the effects underlying the transition of NFs to CAFs in oral squamous cell carcinoma (OSCC) remain unclear. Methods: Five pairs of matching primary NFs and CAFs derived from OSCC patients were sent for RNA sequencing. Epiregulin (EREG) expression was analyzed by IHC in fibroblasts from OSCC patients. The role of EREG in the NF-CAF transition and the consequential effects on OSCC progression were examined by upregulation/downregulation of EREG in NFs/CAFs both in vitro and in vivo. Results: Here, we identified epiregulin (EREG) as the most remarkably upregulated gene in CAFs. High EREG expression in CAFs correlated with higher T stage, deeper invasion and inferior worst pattern of invasion (WPOI) in OSCC patients and predicted shorter overall survival. Overexpression of EREG in NFs activated the CAF phenotype. Mechanistically, the JAK2/STAT3 pathway was enhanced by EREG in parallel with increased IL-6 expression, which could be inhibited by the JAK2 inhibitor AG490. Recombinant IL-6 upregulated the JAK2/STAT3/EREG pathway in a feedback loop. Moreover, EREG-induced CAF activation promoted the epithelial-mesenchymal transition (EMT) necessary for migration and invasion, which was dependent on JAK2/STAT3 signaling and IL-6. In vivo, EREG expression in stroma fibroblasts promoted tumor growth with high stromal α-SMA, phospho-JAK2/STAT3, and IL-6 expression and upregulated EMT in HSC3 cells. Conclusions: EREG is essential for the NF-CAF transformation needed to induce EMT of tumor cells in a JAK2-STAT3- and IL-6-dependent manner in OSCC. [ABSTRACT FROM AUTHOR]

Background: Monocytes, which subdivided into three functional subsets (classical, intermediate, and nonclassical), play important roles in the progression of cancer. The subset composition is altered in several pathologic conditions including cancers. However, the composition and function of circulating monocyte subsets in patients with oral squamous cell carcinoma (OSCC) are still obscure.Methods: The frequencies of monocyte subsets in peripheral blood of patients with OSCC and healthy donors are determined by flow cytometry, and their diagnostic values for OSCC were evaluated. The associations between levels of monocyte subsets and clinicopathological features of patients with OSCC were analyzed using cross-tabulation with the chi-square test.Results: We demonstrated that the frequency of CD14++ CD16+ intermediate monocytes was remarkably increased (P < 0.0001) in OSCC patients compared with healthy controls (7.33% ± 2.56% of total monocytes, n = 68 versus 4.78% ± 1.50% of total monocytes, n = 57). A trend of decrease in CD14++ CD16- classical subset was observed between these two groups (P = 0.0508), whereas no significant difference was detected in CD14+ CD16++ nonclassical subset (P > 0.05). The receiver operating characteristic (ROC) curve analysis indicated that the frequency of intermediate monocytes (AUC = 0.810, P < 0.0001) could be a potential diagnostic biomarker to discriminate patients with OSCC from healthy subjects. Moreover, this parameter was significantly correlated to the worst pattern of invasion (WPOI, P < 0.05) of OSCC tissues.Conclusions: Detection of monocyte subsets in peripheral blood sheds a light on utilizing the frequency of intermediate monocytes as a potential diagnostic biomarker for OSCC. [ABSTRACT FROM AUTHOR]