ICOSLG-associated immunological landscape and diagnostic value in oral squamous cell carcinoma: a prospective cohort study
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ABSTRACT:
SUBMITTER: Dong Y
PROVIDER: S-EPMC10569602 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC10792702 | biostudies-literature
Project description:IntroductionCircular RNAs (CircRNAs), an emerging non-coding RNA, have been demonstrated to be involved in tumorigenesis, metastasis, and cancer progression, and could represent novel potential biomarkers for diagnosing oral squamous cell carcinoma (OSCC). However, no meta-analysis has investigated the diagnostic role of circRNAs in OSCC. Hence, to investigate whether circRNAs could serve as specific biomarkers for OSCC, the present systematic review and meta-analysis evaluated the diagnostic efficiency of circRNAs in patients with OSCC.Materials and methodsA thorough search of online databases (Pubmed, Web of Science, Embase, and the Cochrane Library) was conducted to collect relevant studies up to March 30th, 2021. All eligible studies were case-control studies. The quality of each study was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATA (version 15.1) and Review Manager (version 5.4) were employed to conduct the meta-analysis, and the PRISMA statement was adopted in this study.ResultsA total of 16 studies were included in the meta-analysis, with five studies on upregulated circRNAs, and 11 on downregulated circRNAs. The enrolled studies that met our eligibility criteria all derived from China. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the area under receiver operating characteristics curve (AUC) with the 95% confidence intervals (95% CIs) were 0.74 (0.69-0.79), 0.79 (0.73-0.84), 10.74 (7.81-14.77), 3.50 (2.78-4.45), 0.33 (0.27-0.39) and 0.83 (0.79-0.86), respectively. The subgroup analysis demonstrated that serum, plasma, and saliva specimens had a better diagnostic performance than tissue samples, with a high value of sensitivity, specificity, DOR, and AUC values. The results also showed that the subgroups of upregulated circRNAs and a sample size of ≥100 manifested higher specificity, DOR, and AUC for cancer detection than downregulated circRNAs and a sample size of < 100.ConclusionsA strong association was demonstrated between the dysregulated expression of circRNAs and the diagnosis of OSCC. Hence, circRNAs have the potential to function as promising biomarkers and therapeutic targets for OSCC.Systematic review registrationPROSPERO, number CRD42021256857.
| S-EPMC8295991 | biostudies-literature
Project description:There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs.DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival.Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series.Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.
| S-EPMC3566828 | biostudies-literature
Project description:The aim of this study was to investigate whether there is a correlation between the expressions of four matrix metalloproteinases (MMPs): MMP-2, MMP-7, MMP-9 and MMP-13, and the TNM (tumour-node-metastasis) stages of oral squamous cell carcinoma (OSCC); and to explore the implication of these MMPs in OSCC dissemination. Samples from 61 patients diagnosed with oropharyngeal tumour were studied by immunohistochemistry against MMP-2, MMP-7, MMP-9 and MMP-13. The assessment of immunoreactivity was semi-quantitative. The results showed that MMP-2 and MMP-9 had similar expression patterns in the tumour cells with no changes in the immunoreactivity during tumour progression. MMP-9 always had the highest expression, whereas that of MMP-2 was moderate. MMP-7 showed a significant decrease in expression levels during tumour evolution. MMP-13 had constant expression levels within stage T2 and T3, but showed a remarkable decline in immunoreactivity in stage T4. No significant differences in the MMPs immunoreactivity between tumour cells and stroma were observed. Although strong evidence for the application of MMPs as reliable predictive markers for node metastasis was not acquired, we believe that combining patients' MMPs expression intensity and clinical features may improve the diagnosis and prognosis. Strong evidence for the application of MMPs as reliable predictive markers for node metastasis was not acquired. Application of MMPs as prognostic indicators for the malignancy potential of OSCC might be considered in every case of tumour examination. We believe that combining patients' MMPs expression intensity and clinical features may improve the process of making diagnosis and prognosis.
| S-EPMC4433935 | biostudies-other
Project description:The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). 68Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, 68Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of 68Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3-27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; p = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of 68Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR expression verified the target specificity of 68Ga-NOTA-AE105. Despite the target specificity, the sensitivity of imaging is too low for nodal staging and it cannot replace neck dissection.
| S-EPMC10649042 | biostudies-literature
Project description:Hemostatic complications, ranging from thromboembolism to bleeding, are a significant source of morbidity and mortality in cancer patients. The tumor coagulome represents the multiple genes and proteins that locally contribute to the equilibrium between coagulation and fibrinolysis. We aimed to study the coagulome of Oral Squamous Cell Carcinoma (OSCC) and examine its link to the tumor microenvironment (TME). We used data from bulk tumor DNA/RNA-seq (The Cancer Genome Atlas), single-cell RNA-seq data and OSCC cells in culture. Among all tumor types, OSCC was identified as the tumor with the highest mRNA expression levels of F3 (Tissue Factor, TF) and PLAU (urokinase type-plasminogen activator, uPA). Great inter- and intra-tumor heterogeneity were observed. Single-cell analyses showed the coexistence of subpopulations of pro-coagulant and pro-fibrinolytic cancer cells within individual tumors. Interestingly, OSCC with high F3 expressed higher levels of the key immune checkpoint molecules CD274/PD-L1, PDCD1LG2/PD-L2 and CD80, especially in tumor dendritic cells. In vitro studies confirmed the particularity of the OSCC coagulome and suggested that thrombin exerts indirect effects on OSCC cells. OSCC presents a specific coagulome. Further studies examining a possible negative modulation of the tumor's adaptive immune response by the coagulation process are warranted.
| S-EPMC8773794 | biostudies-literature
Project description:BackgroundThis study aimed to investigate the role of protein disulfide isomerase A3 (PDIA3) in oral squamous cell carcinoma (OSCC) and evaluate its significance as a diagnostic and prognostic biomarker.MethodsComprehensive bioinformatics analysis of the OSCC dataset from The Cancer Genome Atlas (TCGA) was performed. PDIA3 was depleted in CAL27 and SCC25 OSCC cells by transfection with PDIA3-specific siRNA oligos. The effects of PDIA3 downregulation on cell viability, apoptosis, and cell migration were evaluated using CCK8, ELISA, and wound healing assays, respectively.ResultsThe mRNA and protein expression of PDIA3 was significantly up-regulated in OSCC tissues compared to adjacent normal tissues. Knockdown of PDIA3 led to significantly decreased cell viability, increased apoptosis, and suppressed migratory ability in OSCC cells. The Kaplan-Meier survival curve showed that patients with higher PDIA3 expression levels had shorter survival than those with low PDIA3 levels. The receiver operating characteristic (ROC) curve indicated that PDIA3 had high sensitivity and accuracy for detecting OSCC (area under the curve (AUC): 0.917, CI: 0.879-0.955). Univariate and multivariate Cox regression analyses identified PDIA3 as an independent prognostic factor of OSCC. Furthermore, the depletion of PDIA3 inhibited AKT activity in OSCC cells. Gene set enrichment analysis (GSEA) indicated that PDIA3 is involved in various important biological functions and signaling pathways closely related to cancer development.ConclusionPDIA3 plays an oncogenic role in OSCC and represents a good candidate as a diagnostic and prognostic biomarker for OSCC.
| S-EPMC10782160 | biostudies-literature
Project description:BACKGROUND:Although checkpoint blockades have become widely used, the immunological impact in cancer patients, especially those with oral cavity squamous cell carcinoma (OCSCC), has not been well studied. METHODS:The present study assessed the immunological impact of anti-PD-1 (nivolumab) treatment in 10 patients with OCSCC. This involved phenotypic analyses of peripheral blood T-cell subpopulations and their expression of immune mediators prior to and following nivolumab treatment. The focus was on immunological effects of treatment without regard to possible clinical responses. RESULTS:Nivolumab caused a decline in the frequency of blood CD4+ cells but did not affect their expression of IFN-?. However, nivolumab increased the proportion of CD4+ cells expressing the Treg-supporting factor Foxp3. Nivolumab treatment caused an increase in the proportion of CD8+ cells. While their expression of granzyme B increased, it did not attain significance. Analyses of CD8+ cell subpopulations showed nivolumab caused an increase in levels of unconventional CD8dimCD3+ T-cells. It also caused an increase in expression of granzyme B by these unconventional T-cells as well as by the conventional CD8hiCD3+ cells. The CD8hiCD3+ subpopulation also had a near-significant increase in IFN-? expression. Treatment with nivolumab had no effect on the levels of the NK containing CD8dimCD3- subpopulation of cells or their expression of IFN-? or granzyme B. CONCLUSIONS:These results show nivolumab causes opposing effects on CD4+ and CD8+ cell populations, with CD4+ cell levels declining but increasing the proportion of Treg cells, and unconventional CD8+ T-cell levels increasing with increased expression of immune mediators by CD8+ T-cell subpopulations.
| S-EPMC7076935 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC.
| S-EPMC5337388 | biostudies-literature
Project description:BACKGROUND Circular RNAs (circRNAs), a newly-discovered class of non-coding RNAs, have a significant role in the progression of cancers, but the effect of hsa_circ_0086414 in human oral squamous cell carcinoma (OSCC) is still unclear. MATERIAL AND METHODS The circRNAs expression profile in OSCC tissue samples was assessed by high-throughput sequencing. The hsa_circ_0086414 expression level in 55 paired OSCC tissue samples and 2 kinds of OSCC cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the correlation between the hsa_circ_0086414 expression and clinicopathological characteristics of individuals with OSCC was studied. We used receiver operating characteristic (ROC) curves to observe the hsa_circ_0086414 value of diagnosis in OSCC. The network of hsa_circ_0086414-miRNAs-mRNAs was constructed. Gene Ontology (GO), Disease Oncology (DO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out based on sequencing data and bioinformatics predictions. RESULTS Hsa_circ_0086414 expression in OSCC tissue samples and OSCC cells was first discovered to be significantly downregulated compared with the adjacent healthy tissues (AHTs) and normal (HaCaT) cells, respectively. Moreover, its expression level was significantly correlated with stage in TNM, size of tumor, and lymph node metastasis. The area below the ROC curve was 0.749. Hsa_circ_0086414-miRNAs-mRNAs network analysis and GO, DO, and KEGG analyses all demonstrated that hsa_circ_0086414 is correlated with cancer progression to a certain extent. CONCLUSIONS We discovered that hsa_circ_0086414 might be an essential diagnostic biomarker in OSCC. Furthermore, hsa_circ_0086414 could be a target for OSCC therapy.
| S-EPMC6978993 | biostudies-literature