scholarly journals Comprehensive Analysis of the Functions, Prognostic and Diagnostic Values of RNA Binding Proteins in Head and Neck Squamous Cell Carcinoma

Author(s):  
Xueping Ke ◽  
Zhen Fu ◽  
Jingjing Yang ◽  
Shijin Yu ◽  
Tingyuan Yan ◽  
...  

Abstract Background: Increasing evidence has suggested that RNA binding protein (RBP) dysregulation plays an important part in tumorigenesis. Here, we sought to explore the potential molecular functions and clinical significance of RBP and develop diagnostic and prognostic signatures based on RBP in patients with head and neck squamous cell carcinoma (HNSCC). Methods: The Limma package was applied to identify the differently expressed RBPs between HNSCC and normal samples with |log2 fold change (FC)|≥1 and false discovery rate (FDR)<0.05. the immunohistochemistry images from the Human Protein Atlas database The diagnostic signature based on RBP was built by LASSO-logistic regression and random forest and the prognostic signature based on RBP was constructed by LASSO and stepwise Cox regression analysis in training cohort and validated in validation cohort. All these analyses were performed using the R software.Results: A total of 84 aberrantly expressed RBPs were obtained, comprising 41 up-regulated and 43 down-regulated RBPs. Seven RBP genes (CPEB3, PDCD4, ENDOU, PARP12, DNMT3B, IGF2BP1, EXO1) were identified as diagnostic related hub gene and were used to establish a diagnostic RBP signature risk score (DRBPS) model by the coefficients in LASSO-logistic regression analysis and shown high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.998), and in all validation cohorts (AUC > 0.95 for all). Similarly, seven RBP genes (MKRN3, ZC3H12D, EIF5A2, AFF3, SIDT1, RBM24 and NR0B1) were identified as prognosis associated hub genes by least absolute shrinkage and selection operator (LASSO) and stepwise multiple Cox regression analyses and were used to construct the prognostic model named as PRBPS. The area under the curve of the time-dependent receiver operator characteristic curve of the prognostic model were 0.664 at 3 years and 0.635 at 5 years in training cohort and 0.720, 0.777 in the validation cohort, showing a favorable predictive effificacy for prognosis in HNSCC.Conclusions: Our results demonstrate the values of consideration of RBP in the diagnosis and prognosis for HNSCC and provide a novel insights to understand potential role of dysregulated RBP in HNSCC.

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingjuan Lu ◽  
Yongcong Yan ◽  
Bowen Li ◽  
Mo Liu ◽  
Yancan Liang ◽  
...  

PurposeThe biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC using several bioinformatic strategies.Materials and MethodsOSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs using Cox regression and risk score analyses.ResultsWe found that the differentially expressed RBPs were closely related to the defense response to viruses and multiple RNA processes. We identified 10 prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the receiver operating characteristic (ROC) curve (AUC) of the risk score model was 0.781, suggesting that our model exhibited excellent prognostic performance. Finally, we built a nomogram integrating the 10 RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC.ConclusionWe established a novel 10-RBP-based model for OSCC that could enable precise individual treatment and follow-up management strategies in the future.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng Wang ◽  
Xia Xu

Background: Glioblastoma (GBM) is the frequently occurring and most aggressive form of brain tumors. In the study, we constructed an immune-related gene pairs (IRGPs) signature to predict overall survival (OS) in patients with GBM.Methods: We established IRGPs with immune-related gene (IRG) matrix from The Cancer Genome Atlas (TCGA) database (Training cohort). After screened by the univariate regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis, IRGPs were subjected to the multivariable Cox regression to develop an IRGP signature. Then, the predicting accuracy of the signature was assessed with the area under the receiver operating characteristic curve (AUC) and validated the result using the Chinese Glioma Genome Atlas (CGGA) database (Validation cohorts 1 and 2).Results: A 10-IRGP signature was established for predicting the OS of patients with GBM. The AUC for predicting 1-, 3-, and 5-year OS in Training cohort was 0.801, 0.901, and 0.964, respectively, in line with the AUC of Validation cohorts 1 and 2 [Validation cohort 1 (1 year: 0.763; 3 years: 0.786; and 5 years: 0.884); Validation cohort 2 (1 year: 0.745; 3 years: 0.989; and 5 years: 0.987)]. Moreover, survival analysis in three cohorts suggested that patients with low-risk GBM had better clinical outcomes than patients with high-risk GBM. The univariate and multivariable Cox regression demonstrated that the IRGPs signature was an independent prognostic factor.Conclusions: We developed a novel IRGPs signature for predicting OS in patients with GBM.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Lv ◽  
Songtao Han ◽  
Bin Xu ◽  
Yuqin Deng ◽  
Yangchun Feng

Abstract Objective To investigate the predictive value of preoperative complete blood count for the survival of patients with esophageal squamous cell carcinoma. Methods A total of 1587 patients with pathologically confirmed esophageal squamous cell carcinoma who underwent esophagectomy in the Cancer Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2019 were collected by retrospective study. A total of 359 patients were as the validation cohort from January 2015 to December 2016, and the remaining 1228 patients were as the training cohort. The relevant clinical data were collected by the medical record system, and the patients were followed up by the hospital medical record follow-up system. The follow-up outcome was patient death. The survival time of all patients was obtained. The Cox proportional hazards regression model and nomogram were established to predict the survival prognosis of esophageal squamous cell carcinoma by the index, their cut-off values obtained the training cohort by the ROC curve. The Kaplan-Meier survival curve was established to express the overall survival rate. The 3-year and 5-year calibration curves and C-index were used to determine the accuracy and discrimination of the prognostic model. The decision curve analysis was used to predict the potential of clinical application. Finally, the validation cohort was used to verify the results of the training cohort. Results The cut-off values of NLR, NMR, LMR, RDW and PDW in complete blood count of the training cohort were 3.29, 12.77, 2.95, 15.05 and 13.65%, respectively. All indicators were divided into high and low groups according to cut-off values. Univariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29), LMR (< 2.95), RDW (≥15.05%) and PDW (≥13.65%) were risk factors for the prognosis of esophageal squamous cell carcinoma; multivariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29) and LMR (< 2.95) were independent risk factors for esophageal squamous cell carcinoma. Kaplan-Meier curve indicated that age <  60, NLR < 3.52 and LMR ≥ 2.95 groups had higher overall survival (p <  0.05). The 3-year calibration curve indicated that its predictive probability overestimate the actual probability. 5-year calibration curve indicated that its predictive probability was consistent with the actual probability. 5 c-index was 0.730 and 0.737, respectively, indicating that the prognostic model had high accuracy and discrimination. The decision curve analysis indicated good potential for clinical application. The validation cohort also proved the validity of the prognostic model. Conclusion NLR and LMR results in complete blood count results can be used to predict the survival prognosis of patients with preoperative esophageal squamous cell carcinoma.


2019 ◽  
Vol 60 (4) ◽  
pp. 538-545 ◽  
Author(s):  
Zhining Yang ◽  
Binghui He ◽  
Xinyu Zhuang ◽  
Xiaoying Gao ◽  
Dandan Wang ◽  
...  

Abstract The objective of this study was to build models to predict complete pathologic response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC) patients using radiomic features. A total of 55 consecutive patients pathologically diagnosed as having ESCC were included in this study. Patients were divided into a training cohort (44 patients) and a testing cohort (11 patients). The logistic regression analysis using likelihood ratio forward selection was performed to select the predictive clinical parameters for pCR, and the least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomic predictors in the training cohort. Model performance in the training and testing groups was evaluated using the area under the receiver operating characteristic curves (AUC). The multivariate logistic regression analysis identified no clinical predictors for pCR. Thus, only radiomic features selected by LASSO were used to build prediction models. Three logistic regression models for pCR prediction were developed in the training cohort, and they were able to predict pCR well in both the training (AUC, 0.84–0.86) and the testing cohorts (AUC, 0.71–0.79). There were no differences between these AUCs. We developed three predictive models for pCR after nCRT using radiomic parameters and they demonstrated good model performance.


2020 ◽  
Author(s):  
Lei-Lei Wu ◽  
Yu-Xuan Ji ◽  
Yan Zheng ◽  
Xuan Liu ◽  
Yang-Yu Huang ◽  
...  

Abstract PURPOSE: To explore the postoperative prognosis of patients diagnosed with esophageal squamous cell carcinoma (ESCC) of stage T1-3N0M0 using a survival prognostic model (SPM). PATIENTS AND METHODS: Patients diagnosed with stage T1-3N0M0 ESCC from two cancer centers—Sun Yat-sen University Cancer Center (SYSUCC-A/ training cohort: N = 555), SYSUCC-B/ internal validation cohort: N = 241) and Henan Cancer Hospital (HNCH/ external validation cohort: N = 170)—that had undergone esophagectomy between 1995 and 2015 were enrolled in this study. The primary clinical endpoint was overall survival (OS). We have identified and integrated significant prognostic factors for OS by univariate and multivariate Cox regression methods applied in the training cohort to build a SPM that could be validated in the validation cohorts.RESULTS: The OS evaluation by the SPM was comparable in three cohorts (SYSUCC-A: C-index 0.654, SYSUCC-B: C-index 0.630, HNCH: C-index 0.688). Discretization of patients was done using a fixed survival score cutoff of 136.434 based on our SPM determined from the training cohort divided into low- and high-risk subgroups with stratified OS in the validation cohort (SYSUCC-A: hazard ratio [HR] 1.009, 95% confidence intervals [CI], 1.006–1.011, P < 0.001; SYSUCC-B: HR 1.009, 95% CI, 1.004–1.013, P ˂ 0.001; HNCH: HR 1.010, 95% CI 1.005-1.015, P = 0.0017). The 48-month OS in the low-risk subgroup vs. that in the high-risk subgroup was 80.8% vs. 60.9% for SYSUCC-A, 86.4% vs. 60.7% for SYSUCC-B, and 89.7% vs. 64.1% for HNCH. CONCLUSION: We have established and validated a novel SPM that can predict the OS for T1-3N0M0 ESCC patients and could help clinicians to detect subgroups of patients with poor prognosis.


Author(s):  
Hui Peng ◽  
Qiuxing Yang ◽  
Ting Xue ◽  
Qiaoling Chen ◽  
Manman Li ◽  
...  

Objective The present study explored the value of preoperative CT radiomics in predicting lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC). Methods A retrospective analysis of 294 pathologically confirmed ESCC patients undergoing surgical resection and their preoperative chest-enhanced CT arterial images were used to delineate the target area of the lesion. All patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Radiomics features were extracted from single-slice, three-slice, and full-volume regions of interest (ROIs). The least absolute shrinkage and selection operator (LASSO) regression method was applied to select valuable radiomics features. Radiomics models were constructed using logistic regression method and were validated using leave group out cross-validation (LGOCV) method. The performance of the three models was evaluated using the receiver characteristic curve (ROC) and decision curve analysis (DCA). Results A total of 1218 radiomics features were separately extracted from single-slice ROIs, three-slice ROIs, and full-volume ROIs, and 16, 13 and 18 features, respectively, were retained after optimization and screening to construct a radiomics prediction model. The results showed that the AUC of the full-volume model was higher than that of the single-slice and three-slice models. According to LGOCV, the full-volume model showed the highest mean AUC for the training cohort and the validation cohort. Conclusion The full-volume radiomics model has the best predictive performance and thus can be used as an auxiliary method for clinical treatment decision making. Advances in knowledge: LVI is considered to be an important initial step for tumor dissemination. CT radiomics features correlate with LVI in ESCC and can be used as potential biomarkers for predicting LVI in ESCC.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Yang Liang ◽  
Fang Hu ◽  
Yu-Jun Dai ◽  
Yun Wang ◽  
Huan Li

Background: Myelodysplastic syndrome (MDS) was characterized as ineffective hematopoiesis, increased transformation to acute myeloid leukemia (AML), and accompanied by immune system dysfunction. However, the immune signature of MDS remains elusive. Methods: The clinical data (age, sex, international prognostic score system (IPSS), hemoglobin, blast, RBC transfusion dependence, and corresponding subject-level survival) as well as expression profiles of MDS (CD34+ cells) were obtained from Gene Expression Omnibus (GEO: GSE 58831; GSE 114922). A robust prognosis model of immune genes was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis. Survival analysis for prognostic model was carried out through the Kaplan-Meier curve and Log-rank test. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the accuracy of prognostic models. Immune score for different subtype were calculated further by single sample gene set enrichment analysis (ssGSEA). Result: A novel robust immune gene prognostic model indicate that subtype with lower risk score were longer overall survival (OS) than subtype with higher risk score in training cohort (Figure1 A, C). The model was further verified by the validation cohort (Figure1 B, D). The multivariate Cox regression analysis demonstrated the model was an independent prognostic factor for OS prediction with hazard ratios of 56.694 (95% CIs: 9.038−355.648), 3.009 (95% CIs: 1.042−8.692) both in train cohort and external validation cohort respectively (Figure1 G, H). The AUC of 5- year were 0.92 (95% CIs: 0.86 - 0.97) and 0.7 (95% CIs: 0.51 - 0.89) for OS respectively in training cohort and validation cohort (Figure1 E, F). Furthermore, ssGSEA showed higher risk score subtype was significantly associated with higher immune score of check point, human leukocyte antigen (HLA), T cell co-inhibition and type I interferon (IFN) response (Figure1 K-N), which indicating that the poor outcome might be caused by tumor-associated immune response dysfunction partly. Conclusion: We constructed a robust immune gene prognostic model, which have a potential prognostic value for MDS patients and may provide evidence for personalized immunotherapy. Figure Disclosures No relevant conflicts of interest to declare.


Author(s):  
Nattinee Charoen ◽  
Kitti Jantharapattana ◽  
Paramee Thongsuksai

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients. Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors. Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome. Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qian Chen ◽  
Shu Wang ◽  
Jing-He Lang

Abstract Background Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of an efficient prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Results A total of 1541 patients from SEER registries were randomly divided into a training cohort (n = 1079) and a validation cohort (n = 462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for the prediction of 3- and 5-year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773–0.831] and 0.802 (0.769–0.835), respectively, in the training cohort, while 0.746 (0.691–0.801) and 0.770 (0.721–0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in the survival curves of different risk subgroups. Conclusions We have constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bo Qiao ◽  
Min Zhao ◽  
Jing Wu ◽  
Huan Wu ◽  
Yiming Zhao ◽  
...  

Objective. To develop and validate a novel RNA-seq-based nomogram for preoperative prediction of lymph node metastasis (LNM) for patients with oral squamous cell carcinoma (OSCC). Methods. RNA-seq data for 276 OSCC patients (including 157 samples with LNM and 119 without LNM) were downloaded from TCGA database. Differential expression analysis was performed between LNM and non-LNM of OSCC. These samples were divided into a training set and a test set by a ratio of 9 : 1 while the relative proportion of the non-LNM and LNM groups was kept balanced within each dataset. Based on clinical features and seven candidate RNAs, we established a prediction model of LNM for OSCC using logistic regression analysis. Tenfold crossvalidation was utilized to examine the accuracy of the nomogram. Decision curve analysis was performed to evaluate the clinical utility of the nomogram. Results. A total of 139 differentially expressed RNAs were identified between LNM and non-LNM of OSCC. Seven candidate RNAs were screened based on FPKM values, including NEURL1, AL162581.1 (miscRNA), AP002336.2 (lncRNA), CCBE1, CORO6, RDH12, and AC129492.6 (pseudogene). Logistic regression analysis revealed that the clinical N stage (p<0.001) was an important factor to predict LNM. Moreover, three RNAs including RDH12 (p value < 0.05), CCBE1 (p value < 0.01), and AL162581.1 (p value < 0.05) could be predictive biomarkers for LNM in OSCC patients. The average accuracy rate of the model was 0.7661, indicating a good performance of the model. Conclusion. Our findings constructed an RNA-seq-based nomogram combined with clinicopathology, which could potentially provide clinicians with a useful tool for preoperative prediction of LNM and be tailored for individualized therapy in patients with OSCC.


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