Prognostic value of immune checkpoint molecules in head and neck cancer: a meta-analysis.
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ABSTRACT:
SUBMITTER: Jia YQ
PROVIDER: S-EPMC6366990 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Immune checkpoint blockade treatments bring remarkable clinical benefits to fighting several solid malignancies. However, the efficacy of immune checkpoint blockade in breast cancer remains controversial. Several clinical trials of immune checkpoint blockades focused on the effect of CTLA4 and PD1/PDL1 checkpoint inhibitors on breast cancer. Only a small portion of patients benefited from these therapies. Here we systematically investigated the expression of 50 immune checkpoint genes, including ADORA2A, LAG-3, TIM-3, PD1, PDL1, PDL2, CTLA-4, IDO1, B7-H3, B7-H4, CD244, BTLA, TIGIT, CD80, CD86, VISTA, CD28, ICOS, ICOSLG, HVEM, CD160, LIGHT, CD137, CD137L, OX40, CD70, CD27, CD40, CD40LG, LGALS9, GITRL, CEACAM1, CD47, SIRPA, DNAM1, CD155, 2B4, CD48, TMIGD2, HHLA2, BTN2A1, DC-SIGN, BTN2A2, BTN3A1, BTNL3, BTNL9, CD96, TDO, CD200 and CD200R, in different subtypes of breast cancer and assessed their prognostic value. The results showed that the expression patterns of these 50 immune checkpoint genes were distinct in breast cancer. High expression of B7-H3 mRNA was significantly associated with worse overall survival (OS), especially in patients with luminal A and luminal B breast cancer. The mRNA expression levels of TIM-3, ADORA2A, LAG3, CD86, CD80, PD1 and IDO1 had no relationship with OS in breast cancer. High expression levels of CTLA-4 and TIGIT were correlated with favorable prognosis in breast cancer. Interestingly, we observed that B7-H3 expression was negatively correlated with the efficacy of cyclophosphamide (CTX). In summary, our study suggested that B7-H3 has potential prognostic value in breast cancer and is a promising target for immune therapy.
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Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) is the 6th most common cancer globally and commonly presents with locally advanced disease, which has a recurrence rate of around 50% despite aggressive multi-modality treatment involving surgery, radiotherapy and chemotherapy or EGFR inhibition where appropriate. As understanding of the underlying cancer biology and the complex interactions within the tumor microenvironment improves, there is gathering interest in and evidence for the role of immunomodulating agents in the management of HNSCC. Immune checkpoint inhibitors, which aim to hinder the inhibitory interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1, have demonstrated durable improvements in patient outcomes in advanced / metastatic HNSCC, with both pembrolizumab and nivolumab being granted FDA approval in 2016. There are numerous ongoing clinical trials exploring the role of checkpoint inhibitors both as single agents and in combination, administered with established treatment modalities such as chemotherapy and radiotherapy, as well as alongside other novel immune modulators. These trials are not limited to advanced / metastatic HNSCC, but also to the neo-adjuvant or adjuvant settings. As studies complete and more results become available, the role immunotherapy agents will have within the treatment strategies for HNSCC may change, with increasing biomarker selection resulting in personalized therapy aiming to further improve patient outcomes.
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Project description:Glycolysis markers including glucose transporter 1 (GLUT1), monocarboxylate transporter 4 (MCT4), hexokinase 2 (HK2), pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) play vital roles in head and neck squamous cell carcinoma (HNSCC). However, their prognostic value in HNSCC is still controversial. In this meta-analysis, we searched the PubMed, Web of Science and Cochrane Library databases and included thirty-seven studies (3272 patients) that met the inclusion criteria. Higher expression levels of the glycolysis markers in tumor tissues correlated with poorer overall survival (OS; P < 0.001), disease-free survival (DFS; P = 0.03) and recurrence-free survival (RFS; P < 0.001) of HNSCC patients. Subgroup and sensitivity analyses demonstrated that higher expression levels of GLUT1 (P < 0.001), MCT4 (P = 0.002), HK2 (P = 0.002) and PKM2 (P < 0.001) correlated with poorer OS among HNSCC patients. Higher expression of MCT4 (P < 0.001) and PKM2 (P = 0.008) predicted poorer DFS among HNSCC patients. However, GLUT4 expression levels did not associate with clinical outcomes in HNSCC patients. These results demonstrate that glycolysis markers, such as GLUT1, MCT4, HK2 and PKM2, are potential prognostic predictors and therapeutic targets in HNSCC.
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Project description:Sex determining region Y-box 2 (SOX2) has been identified as a putative cancer stem cells (CSCs) marker in Head and Neck Cancers (HNC). However, the clinicopathological and prognostic significance of SOX2 in HNC patients remains controversial. We reviewed the literature by performing a meta-analysis based on the data from 7 studies (9 cohorts) to evaluate the association between SOX2 and clinicopathological/prognostic parameters in patients with HNC. Pooled hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results suggested that high SOX2 expression predicted unfavorable OS (HR: 1.54, 95% CI: 1.09-2.18) and DFS (HR: 1.54, 95% CI: 1.13-2.10) of patients with HNC. In addition, increased SOX2 was also significantly associated with high tumor grade (OR: 1.86, 95% CI: 1.06-3.28), advanced TNM stage (OR: 4.22, 95% CI: 2.62-6.80), lymph node metastasis (OR: 2.25, 95% CI: 1.50-3.35) and distant metastasis (OR: 1.99, 95% CI: 1.26-3.15). Our study suggested that SOX2 expression can be served as a candidate unfavorable prognostic biomarker for HNC patients, indicating that it might be a potential therapeutic target.
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Project description:BackgroundCircular RNAs (circRNAs) have been found to have potential biological applications against tumors in humans. This study aimed to evaluate the diagnostic, prognostic, and clinicopathological value of circRNAs in head and neck squamous cell carcinoma (HNSCC).MethodsThe PubMed, Web of Science, EMBASE, and the Cochrane Library were comprehensively searched for the relevant studies before October 20, 2021. Statistical analysis was performed based on STATA 15.0, Meta-DiSc 1.4, and RevMan 5.3 software.ResultsA total of 55 reports regarding 56 kinds of circRNA were studied in this meta-analysis, including 23, 38, and 26 articles on diagnosis, prognosis, and clinicopathological features, respectively. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) were 0.78, 0.84, and 0.87, respectively. Besides, the upregulation of oncogenic circRNAs was significantly associated with poorer overall survival (OS) (HR=2.25, p < 0.05) and disease-free interval (DFS) (HR=1.92, p < 0.05). In contrast, the elevated expression of tumor suppressor circRNAs was associated with a favorable prognosis (HR=0.50, p < 0.05). In addition, the high expression of oncogenic circRNAs was associated with the tumor size (OR=3.59, p < 0.05), degree of differentiation (OR=1.89, p < 0.05), TNM stage (OR=2.35, p < 0.05), lymph node metastasis (OR=1.85, p < 0.05), and distant metastasis (OR=3.42, p < 0.05). Moreover, the expression of tumor suppressor circRNAs was associated with improved clinicopathological features (lymph node metastasis: OR=0.25, p < 0.05).ConclusionsCircRNAs could serve as potential predictive indicators and be useful for the diagnosis, prognosis, and identification of clinicopathological features in HNSCC.
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Project description:BackgroundThe efficiency of controlling nutritional status (CONUT) score in detecting the prognosis of head and neck cancer (HNC) patients has been investigated in some works, but no consistent findings are obtained. Therefore, this work focused on evaluating the precise prognostic role of CONUT for HNC patients through meta-analysis.MethodsThe effect of CONUT on predicting the prognosis of HNC patients was evaluated through calculating combined hazard ratios (HRs) as well as 95% confidence intervals (CIs). The correlations of CONUT with clinicopathological features of HNC patients were investigated through combined odds ratios (ORs) and 95%CIs. This study used the random-effects model in the case of significant heterogeneity; or else, we selected the fixed-effects model.ResultsThere were eight articles involving 1,478 patients enrolled for the current meta-analysis. We adopted the fixed-effects model for OS and DFS analysis because of the non-significant heterogeneity. As demonstrated by our combined findings, high CONUT score could significantly predict the poor overall survival (OS) (HR = 1.94, 95%CI = 1.55-2.44, p < 0.001) and disease-free survival (DFS) (HR = 1.93, 95%CI = 1.45-2.56, p < 0.001) of HNC. In addition, higher CONUT score was significantly connected to T3-T4 stage (OR = 3.21, 95%CI = 1.94-5.31, p < 0.001) and N1-N3 stage (OR = 3.10, 95%CI = 1.74-5.53, p < 0.001).ConclusionAccording to findings in the present meta-analysis, high CONUT score significantly predicted the prognosis of OS and DFS for HNC patients. Higher CONUT score was also correlated to larger tumor size and LN metastasis in HNC. Due to it is a cost-effective and easily available parameter, CONUT could serve as promising prognostic biomarker for HNC.
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