Higher Expression of SPP1 Predicts Poorer Survival Outcomes in Head and Neck Cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Bie T
PROVIDER: S-EPMC8718292 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Higher Expression of SPP1 Predicts Poorer Survival Outcomes in Head and Neck Cancer.
Journal of immunology research 20211223
Secreted phosphoprotein 1 (SPP1) participated in various biological processes in many cancers, including immune response, tumor progression, and prognosis. However, SPP1 in head and neck squamous cell carcinoma (HNSCC) remains unknown. Clinical-genetic data of HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. The differential expression of SPP1 in HNSCC tissues and adjacent normal tissues was quantified by bioinformatics methods and verified by western blot and other differential ...[more]
Similar Datasets
Project description:The upregulation of cell division cycle associated protein 5 (CDCA5) has been observed in various cancer types. However, the prognostic value of CDCA5 and its underlying mechanism contributing to tumorigenesis in hepatocellular carcinoma (HCC) remain poorly understood. We used tissue microarray (TMA) to evaluate the prognosis of 304 HCC samples based on their CDCA5 expression, and analyzed the genomic features correlated with CDCA5 by using dataset from The Cancer Genome Atlas (TCGA). Compared with adjacent normal tissues, increased expression of CDCA5 was found in HCC tissues. Moreover, higher expression of CDCA5 was associated with inferior OS and DFS outcomes in HCC patients. The enrichment plots showed that the gene signatures in cell cycle, DNA replication and p53 pathways were enriched in patients with higher CDCA5 expression. Meanwhile, statistically higher mutations burdens in TP53 could also be observed in CDCA5-high patients. Integrative analysis based on miRNAseq and methylation data demonstrated a potential association between CDCA5 expression and epigenetic changes. In conclusion, our study provided the evidence of CDCA5 as an oncogenic promoter in HCC and the potential function of CDCA5 in affecting tumor microenvironment.
| S-EPMC7425481 | biostudies-literature
Project description:Various serum biomarkers have been developed for predicting head and neck squamous cell carcinoma (HNSCC) prognosis. However, none of them have been proven to be clinically significant. A recent study reported that the ratio of aspartate aminotransaminase (AST) to alanine aminotransaminase (ALT) had a prognostic effect on non-metastatic cancers. This study aimed to examine the effect of the AST/ALT ratio on the survival of patients with HNSCC. Clinical data of 356 patients with locoregionally advanced HNSCC were collected. The effect of the AST/ALT ratio on overall survival was analyzed using a Cox proportional hazard model. Moreover, recursive partitioning analysis (RPA) was used to divide the patients into groups on the basis of the clinical stage and AST/ALT ratio. The prognostic ability of this grouping was validated using an independent data set (N = 167). The AST/ALT ratio ranged from 0.42 to 4.30 (median, 1.42) and was a prognostic factor for overall survival that was independent of age, primary sites, and tumor stage (hazard ratio: 1.36, confidence interval: 1.08-1.68, P = 0.010). RPA divided patients with stage IVA into the following two subgroups: high AST/ALT (≥2.3) and low AST/ALT (<2.3) subgroups. The 5-year survival rate for patients with stage III, stage IVA with a low AST/ALT ratio, stage IVA with a high AST/ALT ratio, and stage IVB were 64.8%, 49.2%, 28.6%, and 33.3%, respectively (p < 0.001). Compared with the low AST/ALT group, the adjusted hazard ratio for death was 2.17 for high AST/ALT group (confidence interval: 1.02-.22 P = 0.045). The AST/ALT ratio was demonstrated to be a prognostic factor of HNSCC. The ratio subdivided patients with stage IVA into low- and high-risk groups. Moreover, intensified treatment for the high-risk group may be considered.
| S-EPMC5061313 | biostudies-literature
Project description:PURPOSE:We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. EXPERIMENTAL DESIGN:XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). RESULTS:Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44-8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16(INK4a)-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52-4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06-0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36-15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08-0.92, respectively; P = 0.037). CONCLUSIONS:In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment.
| S-EPMC3725262 | biostudies-literature
Project description:Increasing evidence has shown that long non-coding RNAs (lncRNAs) have important biological functions and can be used as a prognostic biomarker in human cancers. However, investigation of the prognostic value of lncRNAs in head and neck squamous cell carcinoma (HNSCC) is in infancy. In the present study, we analyzed the lncRNA expression data in a large number of HNSCC patients (n=425) derived from The Cancer Genome Atlas (TCGA) to identify an lncRNA expression signature for improving the prognosis of HNSCC. Three lncRNAs are identified to be significantly associated with survival in the training dataset using Cox regression analysis. Three lncRNAs were integrated to construct an lncRNA expression signature that could stratify patients of training dataset into the high-risk group and low-risk group with significantly different survival time (median survival 1.85 years vs. 5.48 years; P=0.0018, log-rank test). The prognostic value of this three-lncRNA signature was confirmed in the testing and entire datasets, respectively. Further analysis revealed that the prognostic power of three-lncRNA signature was independent of clinical features by multivariate Cox regression and stratified analysis. These three lncRNAs were significantly associated with known genetic and epigenetic events by means of functional enrichment analysis. Therefore, our results indicated that the three-lncRNA expression signature can predict HNSCC patients' survival.
| S-EPMC6246764 | biostudies-literature
Project description:Although patients having head and neck squamous cell carcinoma (HNSCC) have high mortality, standardized prognostic tools are unavailable. As such, having a validated simple prognostic scoring system to help predict mortality in these high-risk patients is urgently needed. The current study aimed to develop and internally validate a prognostic scoring system for overall mortality in human papillomavirus (HPV)-independent HNSCC patients. Data on 400 consecutive patients from the Cancer Genome Atlas database with a known HPV-RNA negative status were analyzed. A prognostic model to predict patient overall mortality was developed using the logistic regression beta coefficients and a simple risk score was created. The model was internally validated using bootstrap validation with 2000 replications. Five covariates (age, pT, pN, perineural invasion, and EAp53 score) were used in the development of the mortality risk score in the final model. Three risk groups were stratified based on the prognostic scores: low-risk (<96 points), medium-risk (96-121 points), and high-risk (≥122 points) with a survival of 76%, 62% and 35%, respectively. The proposed model presented good discrimination in both the development (AUC = 0.76; 95% CI 0.70, 0.81) and bootstrap validation (AUC = 0.76; 95% CI 0.70, 0.81) with a non-significant Hosmer-Lemeshow chi-square of 6.17 (p = 0.63). The proposed prognostic scoring system is easy to use to predict patient overall mortality and could also help in the appropriate allocation of medical resources while managing HNSCC patients. External validation (including re-calibration if needed) should be conducted to test the model's generalizability in different populations.
| S-EPMC6643134 | biostudies-literature
Project description:IntroductionSurvivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival.MethodsWe measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes.ResultsUsing the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729).ConclusionsSurvivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.
| S-EPMC10916757 | biostudies-literature
Project description:Postoperative radiotherapy or concurrent chemoradiotherapy are routine clinical options for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the benefit of adding chemotherapy to radiotherapy is contested. The present study aimed to develop a gene signature to predict the clinical benefit of postoperative chemoradiotherapy using public data from The Cancer Genome Atlas. A 22-gene signature was established, which demonstrated the best predictive value. Patients were separated into low-score and high-score subgroups based on the expression score of the 22-gene signature. In the high-score subgroup, patients who received chemoradiotherapy demonstrated improved overall survival, relapse-free survival and local regional control compared with those who received radiotherapy alone. However, in the low-score subgroup adding chemotherapy to radiotherapy was associated with worse patient outcomes. The predictive value of the 22-gene signature was independent of the conventional clinical variables. Gene set enrichment analysis revealed that the expression signatures of hypoxia phenotype and stem-like traits were significantly enriched in the low-score subgroup. In addition, the low-score subgroup was associated with the gene sets involved in resistance to anticancer drugs. In conclusion, hypoxia- or stem-like gene expression properties are associated with chemotherapy-resistance in HNSCC. The 22-gene signature may be useful as a predictive marker to help distinguish patients who will benefit from postoperative concurrent chemoradiotherapy.
| S-EPMC6036555 | biostudies-literature
Project description:Gene expression signatures that are predictive of therapeutic response or prognosis are increasingly useful in clinical care; however, mechanistic (and intuitive) interpretation of expression arrays remains an unmet challenge. Additionally, there is surprisingly little gene overlap among distinct clinically validated expression signatures. These "causality challenges" hinder the adoption of signatures as compared to functionally well-characterized single gene biomarkers. To increase the utility of multi-gene signatures in survival studies, we developed a novel approach to generate "personal mechanism signatures" of molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Microarray Expression, computes mechanism scores using rank-weighted gene expression of an individual sample. By comparing head and neck squamous cell carcinoma (HNSCC) samples with non-tumor control tissues, the precision and recall of deregulated FAIME-derived mechanisms of pathways and molecular functions are comparable to those produced by conventional cohort-wide methods (e.g. GSEA). The overlap of "Oncogenic FAIME Features of HNSCC" (statistically significant and differentially regulated FAIME-derived genesets representing GO functions or KEGG pathways derived from HNSCC tissue) among three distinct HNSCC datasets (pathways:46%, p<0.001) is more significant than the gene overlap (genes:4%). These Oncogenic FAIME Features of HNSCC can accurately discriminate tumors from control tissues in two additional HNSCC datasets (n?=?35 and 91, F-accuracy?=?100% and 97%, empirical p<0.001, area under the receiver operating characteristic curves?=?99% and 92%), and stratify recurrence-free survival in patients from two independent studies (p?=?0.0018 and p?=?0.032, log-rank). Previous approaches depending on group assignment of individual samples before selecting features or learning a classifier are limited by design to discrete-class prediction. In contrast, FAIME calculates mechanism profiles for individual patients without requiring group assignment in validation sets. FAIME is more amenable for clinical deployment since it translates the gene-level measurements of each given sample into pathways and molecular function profiles that can be applied to analyze continuous phenotypes in clinical outcome studies (e.g. survival time, tumor volume).
| S-EPMC3266878 | biostudies-literature
Project description:Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status.Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS).A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status.Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.
| S-EPMC3405208 | biostudies-other
Project description:We retrospectively analyzed 129 treatment-naïve head and neck squamous cell carcinomas (HNSCCs) for the expression of programmed death ligand 1 (PD-L1), CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs). We evaluated the relationships among these markers, human papilloma virus (HPV) status, and overall survival (OS). PD-L1 and CMTM6 (combined positive score (CPS) ≥ 1 and ≥ 5) were detected in ~ 70% of HNSCCs. HPV status had insignificant effects on marker expression. Most PD-L1-positive cases showed concomitant CMTM6 expression with comparable staining patterns. While PD-L1 and CMTM6 mRNA expression levels correlated with PD-L1 and CMTM6 protein status, no significant correlation was observed for PD-L1 and CMTM6 mRNA expression. Tumors expressing PD-L1 (p < 0.0001) and/or CMTM6 (p < 0.05) were associated with the best OS. A high density of TILs (p < 0.01), CD8+ T cells (p < 0.001), and CD68/CD163 ratio > 1 were prognostically relevant. In addition to HPV status, PD-L1 and CD8+ T cells, CMTM6 was identified as an independent prognostic factor using a multivariate Cox regression analysis. PD-L1 and CMTM6 correlated with TILs and CD8+ cells but not with HPV. Our results identified CMTM6 as an important interaction partner in the crosstalk between TILs, CD8+ T cells, and PD-L1, which mediates anticancer efficacy. Assessments of CMTM6 may be helpful for prognostic prediction, and it may serve as a reliable biomarker for immunotherapy selection.
| S-EPMC11618569 | biostudies-literature