Prognosis Of Head And Neck Squamous Cell Carcinoma Patients Research Articles

Overexpression of BASP1 Indicates a Poor Prognosis in Head and Neck Squamous Cell Carcinoma.

Objective:Brain abundant membrane attached signal protein 1 (BASP1) was originally identified as a membrane and cytoplasmic protein. Recent studies have shown that BASP1 highly expressed in cancer and promoted the proliferation of cancer. However, the role of BASP1 in head and neck squamous cell carcinoma (HNSCC) is largely unknown. Here, we performed a systematic data analysis to examine whether BASP1 can function as prognostic marker in HNSCC. Methods:In this study, we used Oncomine, and UALCAN, databases to analyze the expression of BASP1 in HNSCC. We used Kaplan-Meier plotter to evaluate the effect of BASP1 on clinical prognosis. In addition, we also analyzed genetic alterations, interaction network, and functional enrichment of BASP1. Results: BASP1 mRNA expression level was remarkably increased in HNSCC than in normal tissues (P=1.624e-12). Moreover, high BASP1 expression was significantly related to poor survival (p=0.00056) in HNSCC patients. In addition, BASP1 gene amplified in 5% of HNSCC patients which contributes to the overexpression of BASP1. Conclusions:These findings suggest that BASP1 was frequently amplified which contributes to the overexpression of BASP1, thereby promoting HNSCC progression. Thus, these results indicate that BASP1 might serve as a biomarker to predict the progression and prognosis of HNSCC patients.

Development and validation of a fourteen- innate immunity-related gene pairs signature for predicting prognosis head and neck squamous cell carcinoma

BackgroundImmune-related genes is closely related to the occurrence and prognosis of head and neck squamous cell carcinoma (HNSCC). At the same time, immune-related genes have great potential as prognostic markers in many types of cancer. The prognosis of HNSCC is still poor currently, and it may be effective to predict the clinical outcome of HNSCC by immunogenic analysis.MethodsRNASeq and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), the MINiML format GSE65858 chip expression data was downloaded from NCBI, and immune-related genes was downloaded from the InnateDB database. Immune-related genes in 519 HNSC patients were integrated from TCGA dataset. By using multivariate COX analysis and Lasso regression, robust immune-related gene pairs (IRGPs) that predict clinical outcomes of HNSCC were identified. Finally, a risk prognostic model related to immune gene pair was established and verified by clinical features, test sets and GEO external validation set.ResultsA total of 699 IRGPs were significantly correlated with the prognosis of HNSCC patients. Fourteen robust IRGPs were finally obtained by Lasso regression and a prognostic risk prediction model was constructed. Risk score of each sample were calculated based on Risk models and divided into the high-risk group (Risk-H) and low Risk group (Risk-L). Risk models were able to stratify the risk in patients with TNM Stage, Age, gender, and smoking history, and the AUC > 0.65 in training set and test set, shows that 14-IRGPs signature in patients with HNSCC has excellent classification performance. In addition, 14-IRGPs had the highest average C index compared with the prognostic characteristics and T, N, and Age of the 3 previously reported HNSCC.ConclusionThis study constructed 14-IRGPs as a novel prognostic marker for predicting survival in HNSCC patients.

Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma.

Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in the world, with low survival and poor quality of life. Autophagy-associated genes (ATGs) have been reported to be involved in the initiation and progression of malignancies. Here, we aimed to investigate the association between autophagy-associated genes and the outcomes in HNSCC patients. Methods We obtained ATGs with prognostic values by analyzing the datasets from The Cancer Genome Atlas (TCGA) and Human Autophagy Database (HADb). The enrichment functions of autophagy differential genes were analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Kaplan-Meier method was applied to the survival curve analysis. A prognostic autophagy-related gene signature was established, and its independence was verified. Results We acquired a total of 529 samples and 232 ATGs; further, we identified 45 genes associated with prognosis and built a prognosis autophagy signature based on risk score of 15 genes. Patients were divided into two groups based on risk scores. The Kaplan-Meier curve illustrated that the survival rate of the high-risk group was significantly lower than that of the low-risk group in both the training group and validation group. The ROC curve revealed that the risk score had the highest AUC value in the 3rd and 5th years, reaching 0.703 and 0.724, which are higher than other risk factors such as gender, age, and TNM stage. The nomogram further confirmed its weight in the prognosis of HNSCC patients. Through KEGG and GO enrichment analyses, we observed that ATGs were involved in the tumorigenesis and invasion of tumor by various mediating pathways. We gained 3 hub genes (MAP1LC3B, FADD, and LAMP1) and further analyzed the survival curves, mutations, differential expressions, and their roles in tumors on the online websites. Conclusion We identified a novel autophagy-related signature that may provide promising biomarker genes for the treatment and prognosis of HNSCC. We need to validate its prognostic value by applying it to the clinic.

Novel Prognostic Model Based on Immune Signature for Head and Neck Squamous Cell Carcinoma.

Background Deciphering the immune characteristics within tumors and identifying the immune signals related to the prognostic factor are helpful for the treatment and management of tumor patients. However, systematic analysis of immune signatures in head and neck squamous cell carcinoma (HNSCC) remains largely unstudied. Methods A total of 718 immune-related genes were extracted from RNA sequencing data from 519 HNSCC patients in the TCGA database, and survival analysis with integrated bioinformatics analyses was performed to build the final predictive prognosis model. Results The 178 survival-associated genes (P < 0.05) participated in important immune functions, including immune cell activation and migration. Multivariate regression analysis using 93 genes (P < 0.01), together with survival-associated clinicopathological parameters, identified 35 independent prognostic factors. The most significant 8 independent factors were CD3E, CD40LG, TNFRSF4, CD3G, CD5, ITGA2B, ABCB1, and TNFRSF13b. The final prognostic model achieved outstanding predictive efficiency with the highest AUC of 0.963. Conclusion Our prognostic model based on the immune signature could effectively predict the prognosis of HNSCC patients, providing novel predictive biomarkers and potential therapeutic targets for HNSCC patients.

The prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma: A gene expression-based study.

Whether tumor mutation burden (TMB) affects prognosis and immune infiltration of tumor patients is controversial. We designed and conducted a multi-omics study with the aim of investigating the prognostic value of TMB and the relationship between TMB and immune infiltration in head and neck squamous cell carcinoma (HNSCC). TMB scores were calculated from the mutation data of 506 HNSCC samples from The Cancer Genome Atlas (TCGA), and the patients were divided into low- and high-TMB groups according to the TMB score quartiles. Differentially expressed genes (DEGs) between the low-TMB and high-TMB groups were identified. Immune cell infiltration and survival analyses were conducted between groups. High TMB in HNSCC patients was associated with a poor prognosis, large primary tumor size, advanced clinical stage and a human papillomavirus (HPV)-negative status. A total of 576 DEGs were identified, and gene set enrichment analysis (GSEA) revealed that the DEGs in the low-TMB group were enriched in immune-related pathways. Four hub genes were significantly associated with prognosis, and mutations in these genes affected immune infiltration. The estimated fractions of B memory cells and CD4+ memory resting cells were higher in the low-TMB group than in the high-TMB group, and B cell and CD4+T cell infiltration was positively correlated with prognosis in HNSCC patients. HNSCC patients with low TMB have better prognoses than those with high TMB, and TMB might affect B cell and CD4+T cell infiltration.

FOXD2-AS1 promotes migration and invasion of head and neck squamous cell carcinoma and predicts poor prognosis.

Aim: To investigate the role of long noncoding RNA FOXD2-AS1 in head and neck squamous cell carcinoma (HNSCC). Materials & methods: The expression and clinical significance of FOXD2-AS1 were analyzed using data from public databases. Transwell assays were used to examine the function of FOXD2-AS1 in HNSCC. The molecular mechanism of FOXD2-AS1 was probed by western blotting. Results: The expression of FOXD2-AS1 was upregulated in HNSCC; it was positively related with the pathological stage as well as with poor prognosis in HNSCC patients. FOXD2-AS1 silencing inhibited HNSCC cell migration and invasion, also influenced the expression of epithelial-mesenchymal transition-related molecules. Conclusion: FOXD2-AS1 was a prognostic marker in patients with HNSCC and may be a favorable novel treatment target for HNSCC.

Slug is a novel molecular target for head and neck squamous cell carcinoma stem-like cells.

The acquisition of stem-like phenotype is partly attributed to the induction of epithelial-mesenchymal transition (EMT). Thus, the activation of factors involved in EMT can be linked to cancer stem cell genesis. However, the underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. Herein, we investigate whether slug, one of the major effectors of EMT, affects the stemness of HNSCC cells. We performed in vitro experiments to determine whether slug gene manipulation can influence the stemness phenotypes, including the capacity for self-renewal, expression of putative stemness markers, chemoresistance, and invasion in HNSCC cells. Further, we identified whether Slug knockout attenuates tumorigenicity of HNSCC cells in vivo. Finally, we examined whether prognosis of HNSCC patients after curative treatment may be affected by the level of slug expression. Overexpression of slug promoted self-renewal of HNSCC cells via activation of sphere formation, the expression of stem cell markers, and induction of chemoresistance to cisplatin. Also, slug overexpression increased the migration and invasion of HNSCC cells in vitro and was mainly observed during the invasion in HNSCC xenograft mouse model. By contrast, slug expression knockdown abrogated their self-renewal capacity, stemness-associated gene expression, and cisplatin chemoresistance. Furthermore, high levels of slug expression correlated with poor prognosis of patients with HNSCC. Inhibition of slug expression may represent a novel therapeutic strategy targeting HNSCC stem-like cells.

A highway to carcinogenesis: the role of IQGAP1, a signaling scaffolding protein, in head and neck cancer development.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide. One of the most critical signaling pathways in HNSCC is the Epidermal Growth Factor Receptor/ Phosphatidylinositol 3-Kinase (EGFR/PI3K) pathway. IQ motif-containing GTPase- activating protein 1 (IQGAP1), a protein upregulated in multiple types of cancer, acts as a scaffold for this pathway and others implicated in cancer. IQGAP1 is overexpressed in HNSCCs, and its overexpression correlates with poorer prognosis in HNSCC patients, indicating that IQGAP1 might be important in HNSCC development. Here, we summarized our recent demonstrating a role of IQGAP1 in promoting HNSCC, at least in part, by scaffolding the EGFR/PI3K signaling pathway.

PD-L1 in combination with CD8+TIL and HIF-1α are promising prognosis predictors of head and neck squamous cell carcinoma.

e18545 Background: Currently, the tumor/node/metastasis (TNM) staging is the most widely used Head and neck squamous cell carcinoma (HNSCC) staging system. However, this classification only provides limit information for the prognosis of HNSCC. Recently, some studies suggest that the level of PD-L1 in tumor cells (TC-PD-L1) or in tumor microenvironment cells (TMC-PD-L1) is a promising biomarker for the prognosis of HNSCC patients. Therefore, in this study, we evaluated the prognostic value of TC-PD-L1, TMC-PD-L1, CD8+ TIL, HIF-1α. In addition, we investigated if incorporated these biomarkers into TNM stage could improve the prognostic value of TNM stage. Methods: A total of 63 patients who underwent surgical resection. The level of PD-L1, CD8+ TIL and HIF-1α was determined by immunohistochemical analysis. The survival of patients was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. The prognostic power of these parameters was evaluated by C-index. Results: We observed that the survival of patients, who had high level of PD-L1 in tumor cells, was significantly shorter than those who had low level of PD-L1. However, the survival of patients who had high level of PD-L1 in tumor microenvironment was significantly longer than patients with low level of PD-L1 in tumor microenvironment. In addition, high level of CD8+ tumor-infiltrating lymphocyte or low level of HIF-1α level suggests a better prognosis. Moreover, we observed that PD-L1 in combination with CD8+tumor-infiltrating lymphocyte and HIF-1α could significantly improve the prognostic effect of current TNM stage. Conclusions: The results of this study suggest that the level of PD-L1, CD8+TIL and HIF-1α is useful prognostic biomarkers for patients with HNSCC. Incorporated these biomarkers into current TNM stage of HNSCC improve the discriminatory capability of TNM stage.

NRF2, p53, and p16: Predictive biomarkers to stratify human papillomavirus associated head and neck cancer patients for de-escalation of cancer therapy.

Patients with HPV associated (HPV+ve) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal cancer, show better treatment response, higher survival rates, and lower risks of recurrence as compared to HPV-ve HNSCC patients. Despite increased sensitivity to treatment modality, HPV+ve HNSCC patients are subjected to the same intensive anti-cancer therapy as HPV-ve HNSCC patients and thus subjecting them to unwarranted long-term toxicity. To identify predictive biomarkers for risk-stratification, we have analyzed the mutational spectrum, and the evidence suggests that gain-of-function mutations in the NRF2 pathway are highly prevalent in HPV-ve HNSCC. At the same time, it is rare in HPV+ve HNSCC tumors. We have reviewed the importance of gain-of-NRF2 function and loss of p53 in the prognosis of HNSCC patients and discussed a predictive scoring system using a combination of HPV status (p16), NRF2 pathway and p53 to stratify HPV+ve HNSCC into good versus poor responders, which could immensely help in guiding future de-escalation treatment approaches in patients with HPV+ve HNSCC.

Identification and Validation of an Immune-Related RNA Signature to Predict Survival of Patients With Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by different molecular subgroups and clinical features. Therefore, it is important to uncover reliable molecular biomarkers for distinguishing different risk patient subgroup. Here, we conducted a multi-omics analysis to examine the joint predictive power of a multi-type RNA signature in the prognosis of HNSCC patients through integration analysis of mRNA, miRNA, and lncRNA expression profiles and clinical data in a large number of HNSCC patients. A multi-type RNA signature (15SigRS) was constructed which can classify patients into the high-risk group and low-risk group with the significantly different outcome [hazard ratio (HR) = 2.718, 95% confidence interval (CI), 2.258–3.272, p < 0.001] in the discovery data set, and subsequently validated in the Cancer Genome Atlas (TCGA) testing data set (HR = 1.299, 95% CI, 1.170–1.442, p < 0.001) and another independent GSE65858 data set (HR = 1.077, 95% CI, 1.016–1.143, p = 0.013). Further multivariate Cox regression analysis and stratification analysis demonstrated the independence of predictive performance of the 15SigRS relative to conventional clinicopathological factors. Furthermore, the 15SigRS has a prior performance in prognostic prediction than other single RNA type-based signatures. Functional analysis suggested that the 15SigRS are involved in immune- or metabolism-related KEGG pathways. In summary, our study demonstrated the potential application of mixed RNA types as molecular markers for predicting the outcome of cancer patients.

Perineural invasion as a prognostic factor in head and neck squamous cell carcinoma: a systematic review and meta-analysis

Background: Squamous cell carcinoma (SCC) is the most common type of head and neck cancer, and head and neck squamous cell carcinoma (HNSCC) was proved to having a high prevalence of perineural invasion (PNI). Although some reports have revealed a relationship between PNI and the prognosis in HNSCC patients, the contribution of PNI to the prognosis remains unclear.Objectives: This study was aimed to comprehensively and quantitatively summarize the prognostic value of PNI for the survival of patients with HNSCC.Material and methods: We conducted PubMed and EMBASE to identify all relevant studies. A meta-analysis and subgroup analysis were performed to clarify the prognostic role of PNI.Results: A total of 18 studies (n = 3894) were included. 989 (25.4%) of the 3894 patients exhibited positive PNI, PNI was shown to be significantly associated with overall survival (OS) [hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.88–4.16], disease-free survival (DFS) (HR = 2.42, 95% CI: 1.92–3.05) and disease-specific survival (DSS) (HR = 2.60, 95% CI: 1.86–3.63).Conclusions: The presence of PNI significantly affected OS, DFS and DSS in patients with HNSCC.

Identification and analysis of genes associated with head and neck squamous cell carcinoma by integrated bioinformatics methods.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide, exhibiting high morbidity and mortality. The prognosis of HNSCC patients has remained poor, though considerable efforts have been made to improve the treatment of this cancer. Therefore, identifying significant differentially expressed genes (DEGs) involved in HNSCC progression and exploiting them as novel biomarkers or potential therapeutic targets for HNSCC is highly valuable.MethodsOverlapping differentially expressed genes (DEGs) were screened out from three independent gene expression omnibus (GEO) datasets and subjected to GO and kyoto encyclopedia of genes and genomes pathway enrichment analyses. The protein–protein interactions network of DEGs was constructed in the STRING database, and the top ten hub genes were selected using cytoHubba. The relative expression of hub genes was detected in GEPIA, Oncomine, and human protein atlas (HPA) databases. Furthermore, the relationship of hub genes with the overall survival and disease‐free survival in HNSCC patients was investigated using the cancer genome atlas data.ResultsThe top ten hub genes (SPP1, POSTN, COL1A2, FN1, IGFBP3, APP, MMP3, MMP13, CXCL8, and CXCL12) could be utilized as potential diagnostic indicators for HNSCC. The relative levels of FN1, APP, SPP1, and POSTN could be associated with the prognosis of HNSCC patients. The mRNA expression of APP and COL1A2 was validated in HNSCC samples.ConclusionThis study identified effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting novel and essential therapeutic targets for HNSCC.

Rh type C-glycoprotein functions as a novel tumor suppressor gene by inhibiting tumorigenicity and metastasis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC), a major histologic subtype of head and neck cancer, presents great mortality and morbidity worldwide. The aim of this study is to discover new potential biomarkers closely correlated with HNSCC progression. In this study, weighted gene co-expression network analysis was applied to construct a co-expression network, and the brown module was identified as the most correlated with HNSCC progression. Hub gene identification combined with survival analyses determined RHCG as a candidate biomarker for cancer progression and prognosis prediction. Further experimental results proved that RHCG was aberrantly downregulated in HNSCC tissues and cell lines. Moreover, decreased RHCG expression was shown to be associated with advanced stage and dismal prognosis in HNSCC patients. Functional assays revealed that RHCG could inhibit cell viability, clonogenicity, cell migration in vitro and suppress tumor formation in vivo. Further bioinformatics study demonstrated that DNA promoter hypermethylation of RHCG could lead to its downregulation and serve as potential prognostic maker in HNSCC. Our study reveals that RHCG acts as a tumor suppressor gene that plays a crucial role in inhibiting tumorigenicity and metastasis in HNSCC, which will shed light on the potential diagnostic and therapeutic strategies for HNSCC.

Metformin enhances gefitinib efficacy by interfering with interactions between tumor-associated macrophages and head and neck squamous cell carcinoma cells.

Tumor-associated macrophages (TAMs) play an important role in drug resistance in many tumors, including head and neck squamous cell carcinoma (HNSCC). However, how TAMs interact with HNSCC cells to induce drug resistance, especially under hypoxic conditions, is unclear. In this study, we investigated the mechanism of TAM-induced gefitinib resistance in HNSCC cells and sought for novel therapeutic strategies. The effects of hypoxia-treated HNSCC cells on the migration and polarization of macrophages were analyzed. Recombinant cytokine proteins and neutralizing antibodies were used as controls. In addition, we assessed the cytotoxic effects of gefitinib on HNSCC cells treated with M2-type macrophage conditioned medium, and carried out a cytokine antibody array analysis, thereby revealing the key factor CCL15. The relationship between serum CCL15 expression levels and prognosis in HNSCC patients was analyzed. In addition, we performed bioinformatic analyses to pursue the mechanisms of CCL15-induced gefitinib resistance. Finally, metformin was used to evaluate the sensitizing effects of gefitinib treatment on HNSCC cells in vitro and in vivo. We found that HNSCC cells recruited macrophages by secreting VEGF and polarized the macrophages to the M2 phenotype through IL-6. Conversely, we found that M2-type TAMs promoted HNSCC cell resistance to gefitinib through paracrine CCL15 signaling. The serum CCL15 levels in HNSCC patients showed a significant correlation with patient prognosis. Furthermore, we found that M2-type TAMs could suppress the sensitivity of HNSCC cells to gefitinib through the CCL15-CCR1-NF-κB pathway. In addition, we found that metformin not only inhibited CCL15 expression in M2-type TAMs enhanced by hypoxia, but also suppressed CCR1 surface expression in HNSCC cells. Encouragingly, we found that metformin sensitized HNSCC cells to gefitinib treatment in vitro and in vivo. Based on our data we conclude that we have identified a novel interaction between M2-type TAMs and HNSCC cells that contributes to gefitinib resistance. We also found that metformin inhibited the cross-talk between macrophages and tumor cells, thereby eliciting therapeutic effects both in vitro and in vivo.

Analysis of lncRNA-Mediated ceRNA Crosstalk and Identification of Prognostic Signature in Head and Neck Squamous Cell Carcinoma.

Long non-coding RNA (lncRNA) can act as ceRNA to regulate the expression of target genes by sponging miRNAs, and therefore plays an essential role in tumor initiation and progression. However, functional roles and regulatory mechanisms of lncRNAs as ceRNAs in head and neck squamous cell carcinoma (HNSCC) remain to be determined. We downloaded RNA sequence profiles from The Cancer Genome Atlas (TCGA) database, and identified the differential RNAs by bioinformatics. Then we analyzed the biological processes of differential expressed RNAs (DER), and established their interaction networks and pathway analysis to find out potential biological effects of these DERs. Besides, we also explored the relationship between the DERs and prognosis of HNSCC patients. We obtained 525 tumor samples and 44 paracancerous controls, and there were 1081 DElncRNAs, 1889 DEmRNAs, and 145 DEmiRNAs. GO and KEGG pathways analysis of these DEmRNAs were mainly involved in “Protein digestion and absorption,” “Calcium signaling pathway,” and “ECM-receptor interaction.” The analysis of the ceRNA network identified 61 DElncRNAs as functional ceRNAs whose dysregulated expression may affect the expression of oncogenes/tumor suppressor genes. Furthermore, univariate and multivariate Cox regression analysis revealed that 4 DElncRNAs, 3 EDmiRNAs, and 6 DEmRNAs can predict survival with high accuracy. Survival analysis found that 4 lncRNAs was related to prognostic, including overexpressed RP11-366H4.1, HOTTIP, RP11-865I6.2, and RP11-275N1.1 patients had a worse survival. In conclusion, through constructing the ceRNA network in HNSCC patients, we identified key lncRNA-miRNA-mRNA network in HNSCC. All the DERs might participate in varieties of pathways in the initiation, progression, and invasion of HNSCC. Furthermore, some miRNAs (hsa-mir-99a, hsa-mir-337, and hsa-mir-137) and mRNAs (NOSTRIN, TIMP4, GRB14, HOXB9, CELSR3, and ADGRD2) may be the prognostic genes of HNSCC. This study provided a new target and theoretical basis for further research on molecular mechanisms and biomarkers.

Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study

BackgroundThe prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups.MethodsWe performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540).ResultsPretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66–2.31) and DFS (HR = 1.90, 95%CI = 1.41–2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses.ConclusionsMeta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.

Prognostic Value of Hematologic Markers in Head and Neck Squamous Cell Carcinoma

The purpose of our study was to investigate the potential prognostic role of pretreatment hematologic markers, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation therapy in our institution. We retrospectively analyzed medical records of 52 patients diagnosed with HNSCC and treated with definitive chemoradiation therapy between 2010 and 2015 at our institution. Demographic data, clinical stage, tumor characteristics and location, date of diagnosis, date of death, and baseline complete count blood were all collected. Pretreatment NLR and PLR were retrospectively calculated and investigated for correlation with overall survival (OS) using the Kaplan-Meier method. Univariate analysis for categorical and descriptive variables was also performed. A total of 52 patients with oral cavity (n=3, 5.8%), oropharyngeal (n=25, 48.1%), laryngeal (n=23, 44.2%), and hypopharingeal (n=1, 1.9%) cancer were included in this study. The mean age was 61.5 ± 9.1 years and the population was predominately male (82.7%). In the overall population, median OS (mOS) were 28 months. In univariate analysis, tumor stage (T2 vs T4a- T4b), nodal stage (N0 vs N2 or N3) and PLR were associated with improved OS (HR 1.003; 95% CI 1.001-1.005; P=.009). The median value of NLR was 3.239 (0.92-23.51) and PLR was 129.56 (51.42-817.93). Using median value as cutoff, NLR and PLR were significantly associated with OS. Patient with NLR > 3.239 had an mOS of 16 months, whereas the mOS for NLR ≤ 3.239 was 84 months (Log-rank P=.050). Patient with PLR > 129.56 had an mOS of 13 months, whereas the mOS for PLR ≤ 129.56 was 84 months (Log-rank P=.050). Using ROC curves, NLR and PLR were also associated with OS. PLR had the greatest area under the curve (AUC) of 0.739 (0.595-0.883; P=.004), and NLR had the AUC of 0.672 (0.506-0.838; P=.039). Our results indicate that pretreatment hematologic markers (NLR and PLR) are associated with prognosis in HNSCC patients treated with chemoradiation therapy, and represent a cost effective and easily measured marker for patient stratification. Further validation in prospective studies is needed, especially in context of immunotherapy.

Identification and validation a TGF-\u03b2-associated long non-coding RNA of head and neck squamous cell carcinoma by bioinformatics method

BackgroundThe role of transforming growth factorβ (TGF-β)-induced tumor progression in advanced malignancy is well established, but the involvement of long non-coding RNAs (lncRNAs) in TGF-β signaling remains unclear. This study aimed to identify TGF-β-associated lncRNAs in head and neck squamous cell carcinoma (HNSCC).MethodsExpression profiling of lncRNAs was obtained using Gene Expression Omnibus and The Cancer Genome Atlas. Real-time quantitative PCR was used to analyze the expression of EPB41L4A-AS2 in HNSCC cell line. We used bioinformatics resources (DAvID) to conduct Gene Ontology biological processes and KEGG pathways at the significant level. Wound healing assay, cell migration and invasion assays, were used to examine the effects of EPB41L4A-AS2 on tumor cell metastasis in vivo. Protein levels of EPB41L4A-AS2 targets were determined by western blot.ResultsA novel TGF-β-associated lncRNA, EPB41L4A-AS2, was found downregulated by TGF-β and associated with invasion and metastasis. The relationship of EPB41L4A-AS2 with the clinicopathological features and prognosis of HNSCC patients was evaluated. Bioinformatic analyses revealed that EPB41L4A-AS2 may be involved in processes associated with the tumor-associated signaling pathway, especially the TGF-β signaling pathway. Furthermore, a TGF-β-induced epithelial-to-mesenchymal transition (EMT) model was established. Low EPB41L4A-AS2 expression was determined, and overexpression of this gene inhibited cell migration and invasion in the EMT model. Moreover, EPB41L4A-AS2 suppressed TGFBR1 expression.ConclusionsEPB41L4A-AS2 might serve as a negative regulator of TGF-β signaling and as an effective prognostic biomarker and important target in anti-metastasis therapies of HNSCC patients.