Clinical Significance of miR-149 in the Survival of Patients with Laryngeal Squamous Cell Carcinoma.
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ABSTRACT:
SUBMITTER: Xu Y
PROVIDER: S-EPMC4925956 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimTreatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population.MethodsClinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated.ResultsTwo hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively).ConclusionIn our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS.
| S-EPMC6867599 | biostudies-literature
Project description:Aldosterone reductase family 1 member B10 (AKR1B10) is a nicotinamide adenine dinucleotide phosphate (reduced coenzyme II)-dependent oxidoreductase, and its biological functions include carbonyl detoxification, hormone metabolism, osmotic adjustment, and lipid synthesis. Studies suggested that AKR1B10 is a new biomarker for cancer based on its overexpression in epithelial tumors, such as breast cancer, cervical cancer, and lung cancer. At present, studies on the expression of AKR1B10 in laryngeal cancer have not been reported. However, we found that AKR1B10 is upregulated in laryngeal carcinoma, and its expression was negatively correlated with the degree of differentiation. In addition, AKR1B10 expression was positively correlated with tumor size; lymph node metastasis; alcohol use; and Ki-67, mutant p53, and matrix metalloproteinase 2 expression. AKR1B10 was overexpressed in Hep-2 laryngeal carcinoma cells. Oleanolic acid inhibited AKR1B10 activity and expression in Hep-2 cells and suppressed Hep-2 cell proliferation, migration, and invasion. Therefore, AKR1B10 may be related to the development of laryngeal carcinoma, suggesting its use as a prognostic indicator for laryngeal cancer.
| S-EPMC8440551 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. We aimed to establish a lncRNA signature and a nomogram incorporating the genomic and clinicopathologic factors to improve the accuracy of survival prediction for laryngeal squamous cell carcinoma (LSCC).MethodsA LSCC RNA-sequencing (RNA-seq) dataset and the matched clinicopathologic information were downloaded from The Cancer Genome Atlas (TCGA). Using univariable Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a thirteen-lncRNA signature related to prognosis. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with the TNM staging system by C-index and receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate the clinical value of our nomogram.ResultsThirteen overall survival- (OS-) related lncRNAs were identified, and the signature consisting of the selected thirteen lncRNAs could effectively divide patients into high-risk and low-risk subgroups, with area under curves (AUC) of 0.89 (3-year OS) and 0.885 (5-year OS). Independent factors derived from multivariable analysis to predict survival were margin status, tumor status, and lncRNA signature, which were all assembled into the nomogram. The calibration curve for the survival probability showed that the predictions based on the nomogram coincided well with actual observations. The C-index of the nomogram was 0.82 (0.77-0.87), and the area under curve (AUC) of the nomogram in predicting overall survival (OS) was 0.938, both of which were significantly higher than the traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage.ConclusionAn inclusive nomogram for patients with LSCC, comprising genomic and clinicopathologic variables, generates more accurate estimations of the survival probability when compared with TNM stage alone, but more data are needed before the nomogram is used in clinical practice.
| S-EPMC6886334 | biostudies-literature
Project description:The present study aimed to investigate the expression levels and clinical significance of microRNA (miR)-203 and miR-133b in laryngeal carcinoma. A total of 154 patients with laryngeal carcinoma (research group) along with 100 healthy individuals (control group) were enrolled in the study. The patients were admitted to Yidu Central Hospital of Weifang (Weifang, China) from February 2016 to October 2018. Fasting venous blood (5 ml) was extracted from all subjects to determine the expression levels of serum miR-203 and miR-133b by reverse transcription-quantitative polymerase chain reaction (PCR) and to compare them among patients with different pathological characteristics. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic values of miR-203 and miR-133b for laryngeal carcinoma. The research group showed significantly lower expression levels of miR-203 and miR-133b than the control group (P<0.05). According to ROC curve analysis, when the cut-off value was 0.659, the sensitivity and specificity of miR-203 in diagnosing laryngeal carcinoma were 60.00 and 90.26%, respectively, whereas when the cut-off value was 1.398, the sensitivity and specificity of miR-133b were 55.00 and 87.66%, respectively. The sensitivity and specificity of the joint detection were 70.00 and 83.77%, respectively, when the cut-off value was 0.416. In the research group, miR-203 was expressed significantly different in patients with different pathological stages and tumor types (P<0.050). The expression of miR-133b varied significantly in patients with different pathological stages, differentiation degrees and lymph node metastasis (P<0.050). In conclusion, miR-203 and miR-133b were expressed at low levels in patients with laryngeal carcinoma. The expression of miR-203 was related to tumor-node-metastasis (TNM) stage and tumor type, whereas the expression of miR-133b was related to TNM stage, differentiation degree, as well as lymph node metastasis. Joint detection of miR-203 and miR-133b is expected to be an excellent marker for the diagnosis and treatment of laryngeal carcinoma.
| S-EPMC7491041 | biostudies-literature
Project description:Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1-9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.
| S-EPMC7690434 | biostudies-literature
Project description:Recent studies have observed that lncRNAs (long non-coding RNAs) are involved in the progression of various tumours including tongue squamous cell carcinoma (TSCC). Recently, a new lnRNA, GACAT1, has been firstly identified in gastric cancer. However, its potential role in TSCC remains unknown. In this reference, we observed that GACAT1 was overexpressed in TSCC samples and cell lines. Of 25 TSCC specimens, GACAT1 expression was overexpressed in 18 patients (18/25, 72%) compared to non-tumour specimens. Ectopic expression of GACAT1 induced cell growth and migration and promoted epithelial to mesenchymal transition in TSCC. In addition, ectopic expression of GACAT1 decreased miR-149 expression in SCC1 cell. We observed that miR-149 expression was down-regulated in TSCC cell lines. Moreover, we observed that GACAT1 expression was negatively correlated with miR-149 expression. GACAT1 overexpression induced TSCC cell growth and migration via regulating miR-149 expression. These data provided that GACAT1 played an oncogenic role in the progression of TSCC partly through modulating miR-149 expression.
| S-EPMC8419168 | biostudies-literature
Project description:The role of microRNA (miRNA)-452-5p in lung squamous cell carcinoma (LUSC) remains unclear. Therefore, the present systematic study was performed to investigate the clinical significance and the rudimentary mechanism of the function of miR-452-5p in LUSC. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to confirm the expression level and clinical value of miR-452-5p in LUSC. Using online databases and bioinformatic software, gene ontology (GO), pathway and protein-protein interaction (PPI) analyses of miR-452-5p target genes were performed to examine the molecular mechanism of miR-452-5p. The association between the expression of miR-452-5p and that of its hub genes was verified using TCGA. Based on TCGA data on 387 clinical specimens, the expression of miR-452-5p in LUSC was significantly increased compared with adjacent lung tissues (7.1525±1.39063 vs. 6.0885±0.35298; P<0.001). The expression levels of miR-452-5p were significantly correlated with age (P=0.001) and tumor-node metastasis stage (P=0.028). Furthermore, the increased expression of miR-452-5p in LUSC compared with non-cancerous tissue [standard mean deviation (SMD), 0.372; 95% confidence interval (CI), 0.020-0.724; z=2.07; P=0.038] was validated by a meta-analysis of 720 clinical samples. The GO and pathway analyses revealed that miR-452-5p target genes were mainly enriched in the 'regulation of transcription', 'nucleoplasm', 'protein binding' and 'cell cycle' pathways. A total of 10 hub genes were identified by PPI analysis, and 5 hub genes (SMAD4, SMAD2, CDKN1B, YWHAE and YWHAB) were significantly enriched in the 'cell cycle' pathway. The expression of CDKN1B was negatively correlated with miR-452-5p (P=0.003). It was concluded that miR-452-5p may serve an essential role in the occurrence and progression of LUSC by targeting CDKN1B, which is involved in the cell cycle.
| S-EPMC5876433 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are novel transcripts that may play important roles in cancer. Our study aimed to resolve the lncRNA profile of larynx squamous cell carcinoma (LSCC) and to determine its clinical significance. The global lncRNA expression profile in LSCC tissues was measured by lncRNA microarray. Distinctly expressed lncRNAs were identified and levels of AC026166.2-001 and RP11-169D4.1-001 lncRNAs in 87 LSCC samples and paired adjacent normal tissue were analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The clinical significance of these lncRNAs in laryngeal cancer was analyzed and survival data were estimated by the Kaplan-Meier method and the log-rank test. A receiver operating characteristic (ROC) curve was constructed to check the diagnostic value. In the lncRNA expression profile of tumor samples, 684 lncRNAs were upregulated and 747 lncRNAs were downregulated (fold-change >2.0). Of these, AC026166.2-001 and RP11-169D4.1-001 were distinctly dysregulated, with AC026166.2-001 exhibiting lower expression in cancer tissues and RP11-169D4.1-001 higher expression. We verified that both AC026166.2-001 and RP11-169D4.1-001 were expressed at a lower level in cervical lymph nodes compared with paired laryngeal cancer tissues and paired normal tissues. RP11-169D4.1-001 levels were positively correlated with lymph node metastasis (P = 0.007). From the survival analysis, decreased levels of AC026166.2-001 and RP11-169D4.1-001 were associated with poorer prognosis. The area under the ROC curve was up to 0.65 and 0.67, respectively, and the cut-off point of ΔCt was 11.23 and 10.53, respectively. AC026166.2-001 and RP11-169D4.1-001 may act as novel biomarkers in LSCC and may be potential therapeutic targets for LSCC patients. Both AC026166.2-001 and RP11-169D4.1-001 could be independent prognostic factors for survival in LSCC.
| S-EPMC4171522 | biostudies-literature
Project description:Laryngeal squamous cell carcinoma (LSCC) accounts for 95% of laryngeal cancer incidence. Tobacco use has been shown to have a linear association with the development of the disease. While early diagnosis and treatment of LSCC are critical in improving the 5-year survival rate and quality of life, diagnosis of early-stage LSCC remains challenging because of the unapparent symptoms. Here, we report that miR-506, a critical regulator in many types of cancers, is aberrantly suppressed in LSCC patient tissues and cultured cancer cells. This is likely responsible for the enhanced production of YAP1 protein, a transcriptional factor that is well known for its oncogenic roles in LSCC malignancy. Statistical analysis has confirmed that the expression levels of miR-506 and YAP1 are strongly correlated with the malignant statuses of patient tumors. Restoring the expression level of miR-506 in cultured LSCC cells significantly inhibited proliferation, migration and invasion of the cells. The miR-506 and YAP1 regulatory network seems to affect at least pathways involved in apoptosis. Our study, for the first time, has demonstrated a tumor suppressive role of miR-506 in LSCC. This opens new opportunities for further exploring the molecular details of the development of the disease and thus will facilitate the development of novel diagnosis and therapeutic strategies.
| S-EPMC6606012 | biostudies-literature
Project description:To the best of our knowledge, this is the first study established a nomogram to predict survival probability in Asian patients with LSCC. A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application. Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intent surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in the present study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models' concordance. The C-index of the nomogram was 0.73 (0.68-0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage. A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.
| S-EPMC7432998 | biostudies-literature