FDG-PET predicts bone invasion and prognosis in patients with oral squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Lin NC
PROVIDER: S-EPMC8313663 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients.MethodsThe mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups.ResultsA prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator's contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status.ConclusionThis study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.
| S-EPMC8290602 | biostudies-literature
Project description:BackgroundThe molecular mechanisms involved in the invasion of bone by oral squamous cell carcinomas (OSCC) are poorly understood, and little is known about the role of cancer-associated fibroblasts (CAF), the presence of which confers a poor prognosis.MethodsClinicopathological data from 277 OSCC cases involving bone resections were reviewed, and 32 cases thoroughly analysed histologically. Immunohistochemistry was used to examine αSMA, RANKL and OPG. Western blotting and qPCR were used to assess myofibroblast (CAF-like) differentiation, RANKL and OPG expression in vitro, and RANKL secretion was analysed by ELISA. Osteoclastogenesis was examined using TRAP staining, multinucleation and pit forming assays.ResultsFibrous stroma intervened between tumour and bone in the majority of cases, with no direct contact between cancer cells and bone. RANKL and OPG, two proteins key to regulating bone resorption, were expressed in tumour cells as well as fibrous stroma adjacent to bone and αSMA-positive myofibroblastic CAF were consistently seen infiltrating into bone ahead of tumour cells. Human primary osteoblasts cultured with conditioned media from human OSCC-derived cells and human primary CAF showed a significant increase in RANKL and a decline in OPG mRNA expression. RANKL secretion was significantly increased in primary oral fibroblasts induced to differentiate into a CAF-like phenotype by transforming growth factor-β1 (TGF-β1) treatment and in primary CAF. Indirect co-culture of murine macrophages with conditioned media from CAF (experimentally derived and isolated from OSCCs) resulted in a marked increase in osteoclastogenesis (in excess of that provoked by cancer cells) determined by tartrate-resistant acid phosphatase activity, multinucleation and resorption pit formation.ConclusionsThis study is the first to describe a functional role for CAFs in bone invasion and turnover, identifying a novel potential therapeutic target and diagnostic indicator in this difficult to treat bone invasive malignancy.
| S-EPMC5589989 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of β-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-β (RARβ) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARβ expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARβ expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARβ had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARβ are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.
| S-EPMC6877303 | biostudies-literature
Project description:High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment. RUNX3 knockdown induced cell cycle arrest at the G1 and G2 phases and promoted G2 arrest by TGF-β in Ca9.22 OSCC cells. RUNX3 knockdown also inhibited both the basal and TGF-β-induced epithelial-to-mesenchymal transition by increasing E-cadherin expression and suppressing the nuclear translocation of β-catenin. In addition, the expression and TGF-β-mediated induction of parathyroid hormone-related protein (PTHrP), one of key osteolytic factors, was blocked in RUNX3-knockdown OSCC cells. Furthermore, treating human osteoblastic cells with conditioned medium derived from RUNX3-knockdown OSCC cells reduced the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin ratio compared with treatment with conditioned medium from RUNX3-expressing cells. These findings indicate that RUNX3 expression in OSCC cells contributes to their bone invasion and the resulting osteolysis by inducing their malignant behaviors and production of osteolytic factors. RUNX3 alone or in combination with TGF-β and PTHrP may be a useful predictive biomarker and therapeutic target for bone invasion by oral cancer.
| S-EPMC5354716 | biostudies-literature
Project description:The objective of this review is to evaluate the diagnostic accuracy of imaging methods for detection of mandibular bone tissue invasion by squamous cell carcinoma (SCC). A systematic review was carried out of studies in MEDLINE, SciELO and Science Direct, published between 1960 and 2012, in English, Spanish or German, which compared detection of mandibular bone tissue invasion via different imaging tests against a histopathology reference standard. Sensitivity and specificity data were extracted from each study. The outcome measure was diagnostic accuracy. We found 338 articles, of which 5 fulfilled the inclusion criteria. Tests included were: CT (four articles), MRI (four articles), panoramic radiography (one article), positron emission tomography (PET)/CT (one article) and cone beam CT (CBCT) (one article). The quality of articles was low to moderate and the evidence showed that all tests have a high diagnostic accuracy for detection of mandibular bone tissue invasion by SCC, with sensitivity values of 94% (MRI), 91% (CBCT), 83% (CT) and 55% (panoramic radiography), and specificity values of 100% (CT, MRI, CBCT), 97% (PET/CT) and 91.7% (panoramic radiography). Available evidence is scarce and of only low to moderate quality. However, it is consistently shown that current imaging methods give a moderate to high diagnostic accuracy for the detection of mandibular bone tissue invasion by SCC. Recommendations are given for improving the quality of future reports, in particular provision of a detailed description of the patients' conditions, the imaging instrument and both imaging and histopathological invasion criteria.
| S-EPMC3667522 | biostudies-other
Project description:The aim of the present study was to investigate the association between cluster of differentiation (CD) 164 expression with clinicopathological parameters and prognosis among patients with oral cavity squamous cell carcinoma (OSCC). The present study retrospectively reviewed 70 patients with OSCC who underwent curative primary surgery. A number of patients subsequently received postoperative chemoradiotherapy although the specimens were not exposed to radiation or chemotherapy prior to anti-CD164 antibody immunohistochemical staining. CD164 overexpression was arbitrarily defined as exhibiting an H-score of ≥120. Univariate and multivariate analyses were performed for sex, age, American Joint Committee on Cancer stage, tumour location, histological grade, surgical margin and H-score. The 5-year overall survival rate was 54.4% and the median follow-up time was 46 months for surviving patients. Univariate analyses revealed that a low overall survival rate was associated with advanced-stage disease (P<0.001), buccogingival tumour location (P=0.038) and a CD164 H-score of <120 (P=0.016). Multivariate Cox's regression analyses revealed that poor overall survival rate was associated with advanced-stage disease (P=0.001) and a CD164 H-score of <120 (P=0.04). CD164 overexpression in OSCC was associated with favourable survival rate. Thus, CD164 expression may be a clinically useful predictor of prognosis in patients with OSCC.
| S-EPMC5661421 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Patients with oral squamous cell carcinoma (OSCC), a common malignancy in Asian countries, have a poor prognosis. We investigated the role of Krüppel-like factor 17 (KLF17) and its prognostic significance in OSCC. MATERIALS AND METHODS:KLF17 expression was measured by immunohistochemical staining of specimens from 283 patients with OSCC. We analyzed correlations between KLF17 expression and clinicopathologic features and between KLF17 expression and overall survival. The prognostic value of KLF17 was tested using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS:Among the 283 patients, high KLF17 expression was significantly associated with an early OSCC stage and low T-value (p = 0.033 and p = 0.036, respectively). The five-year survival rates were better in patients with high KLF17 expression than with low expression (66.5% and 49.6%, respectively). The prognostic role of KLF17 was further confirmed through multivariate analysis (hazard ratio 1.506, 95% confidence interval 1.034-2.191, p = 0.033). The prognostic value was more significant in patients with a history of betel quid chewing or with a low T-value. CONCLUSIONS:High KLF17 expression can serve as a marker for a favorable prognosis in patients with OSCC. The prognostic role of KLF17 is more significant in patients with a history of betel quid chewing or a low T-value.
| S-EPMC7073896 | biostudies-literature
Project description:BACKGROUND:Deregulated inflammation and immune deficit both intricately associate with cancer initiation and progression, which have been increasingly exploited as prognostic biomarkers and therapeutic targets. Recently, systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte and platelet counts serves as a novel and powerful cancer biomarker with prognostic significance in multiple types of malignancies. Here, we sought to evaluate the prognostic value of preoperative SII in patients with primary oral squamous cell carcinoma (OSCC) after curative resection. METHODS:Two independent cohorts with a total number of 309 patients with OSCC from two tertiary referral hospitals were included and defined as training (Nanjing, 138) and validation (Wuxi, 171) cohort, respectively. Preoperative SII in both cohorts was calculated and its optimal cutoff value was initially determined by X-tile software in the training cohort and then verified in the validation cohort. RESULTS:Our data indicated that high SII (??484.5) was significantly associated with larger tumor size (P?<?0.05, Chi square test), reduced overall and disease-free survival (Kaplan-Meir, P?<?0.05, Log-rank test). Univariate and multivariate analyses further revealed that SII was an independent prognostic predictor for patient survival. Moreover, the area under receiver operating characteristic curve of SII for survival was significantly greater or comparable to other well-established prognostic parameters, indicative of its satisfactory prediction accuracy and specificity. CONCLUSIONS:Our findings reveal that high preoperative SII associates with poor outcome and serves as a non-invasive, low-cost and powerful prognostic predictor for patients with OSCC. This inflammation/immune-related biomarker holds translational potentials to supplement currently prognostic regime to better stratification of patients and treatment planning.
| S-EPMC6299596 | biostudies-literature
Project description:Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva. We performed next-generation sequencing of the TNFα-treated OSCC cells and showed marked overexpression of over 180 genes distributed among clusters related to neutrophil recruitment, invasion, and invadopodia. At the molecular level, TNFα treatment increased phosphoinositide 3-kinase (PI3K)-mediated invadopodia formation and matrix metalloproteinase (MMP)-dependent invasion. We show here that TNFα promotes a pro-inflammatory and pro-invasion phenotype leading to the recruitment and activation of inflammatory cells in a paracrine mechanism. Increased TNFα in the tumor microenvironment tips the balance towards invasion leading to decreased overall survival and disease-free survival. This represents a significant advancement of oral cancer research and will support new treatment approaches to control OSCC invasion and metastasis.
| S-EPMC6044370 | biostudies-literature
Project description:This study aims to determine whether semiquantitative parameters obtained from both the primary tumor and metastatic pelvic lymph nodes (PLN) diagnosed in fluoro-18-deoxy-glucose positron emission tomography (FDG-PET-CT) are associated with disease-free survival (DFS), local control (LC), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with locally advanced squamous cervical cancer (LACC) and metastatic pelvic lymph nodes. Retrospective analysis was performed on 93 female patients with FIGO IIIC1. The median age was 53 years (27-75). The PET parameters both in the primary tumor and metastatic pelvic lymph nodes, including SUVmax, SUVmean, TLG, MTV, heterogeneity, along with clinical variables, before radical cisplatin-based radiochemotherapy (RCT) were analyzed. The p-values < 0.05 were considered statistically significant. Median follow-up was 38 months (4.5-92.6). Three years and five years OS were 75% and 70% respectively. Patients with SUVmax above 12.6, SUVmean above 7.6 and with TLG in tumors >245.7 lived longer (p < 0.05). The higher SUVmax or SUVmean reduced increased DMFS (HR 0.3 95%CI 0.56-0.96 and 0.59 95%CI 0.37-0.93). The clinical factors and other FDG PET CT parameters were not found to be statistically relevant in terms of OS, DFS, DM and LC. This study is the first report showing that in LACC patient population with PLN involvement treated with definitive RCT, high SUVmean, SUVmax and TLG of the primary tumor in FDG-PET-CT were linked with longer OS. Lower SUVmean and SUVmax were linked with shorter DMFS. None of the clinical factors and the nodal FDG-PET-CT parameters influenced the outcome.
| S-EPMC8073234 | biostudies-literature