Higher Expression of SPP1 Predicts Poorer Survival Outcomes in Head and Neck Cancer.
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ABSTRACT:
SUBMITTER: Bie T
PROVIDER: S-EPMC8718292 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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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.
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Project description:ImportanceThe mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood.ObjectiveTo test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival.DesignRetrospective cohort study.SettingAcademic Medical Center (Massachusetts General Hospital, Boston).Participants240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging.Measurements18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV).ResultsAmong individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001).Conclusions and relevanceAmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.
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