Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer

Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear.Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated.Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa.Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.

Low Circulating Monocytes Is in Parallel With Lymphopenia Which Predicts Poor Outcome in Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis-Associated Interstitial Lung Disease

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) may progress rapidly and lead to high mortality within 6 or 12 months. Except for reported prognostic factors, simple but powerful prognostic biomarkers are still in need in practice. In this study, we focused on circulating monocyte and lymphocyte counts and their variation tendency in the early stage of ILD. A total of 351 patients from two inception anti-MDA5 antibody-positive cohorts were included in this study, with various treatment choices. Lymphocyte count remained lower in the first month after admission in the non-survivor patients. Although baseline monocyte count showed no significant differences, average monocyte count in the following 4 weeks was also lower in the non-survivor group. Based on the C-index and analysis by the “survminer” R package in the discovery cohort, we chose 0.24 × 109/L as the cutoff value for Mono W0-2, 0.61 × 109/L as the cutoff value for lymph W0-2, and 0.78 × 109/L as the cutoff value for peripheral blood mononuclear cell (PBMC) W0-2, to predict the 6-month all-cause mortality. The Kaplan–Meier survival curves and adjusted hazard ratio with age, gender, and the number of immunosuppressants used all validated that patients with lower average monocyte count, lower average lymphocyte count, or lower average PBMC count in the first 2 weeks after admission had higher 6-month death risk, no matter in the validation cohort or in the pooled data. Furthermore, flow cytometry figured out that non-classical monocytes in patients with anti-MDA5 antibody-positive DM were significantly lower than healthy controls and patients with DM without anti-MDA5 antibodies. In conclusion, this study elucidated the predictive value of monocyte and lymphocyte counts in the early stage and may help rheumatologists to understand the possible pathogenesis of this challenging disease.

Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer

Background Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC. Methods Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by the C-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method. Results At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P < 0.001). Multivariate analyses revealed that N stage (P < 0.001), harvested lymph nodes (P = 0.021), and CLR (P = 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superior C-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697), P = 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P < 0.001). Conclusions The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.

Identification of Epithelial Mesenchymal Transition-Related lncRNAs Associated with Prognosis and Tumor Immune Microenvironment of Hepatocellular Carcinoma

Purpose. The long noncoding RNAs (lncRNAs) play the important role in tumor occurrence and progression, and the epithelial to mesenchymal transition (EMT) is the critical process for tumor migration. However, the role of EMT-related lncRNA in hepatocellular carcinoma (HCC) has not been elucidated. Methods. In this study, we selected the EMT-related lncRNAs in HCC by using data from The Cancer Genome Atlas database (TCGA). Two prognostic models of the overall survival (OS) and relapse-free survival (RFS) were constructed and validated through Cox regression model, Kaplan-Meier analysis, and the receiver-operating characteristic (ROC) curves. The unsupervised clustering analysis was utilized to investigate the association between EMT-lncRNAs with tumor immune microenvironment. ESTIMATE algorithm and gene set enrichment analysis (GSEA) were used to estimate tumor microenvironment and associated KEGG pathways. Results. Two EMT-related lncRNA prognostic models of OS and RFS were constructed. Kaplan-Meier curves showed the dismal prognosis of OS and RFS in the group with high-risk score. The ROC curves and AUC values in two prognostic models indicated the discriminative value in the training set and validation set. Patients with HCC were clustered into two subgroups according the unsupervised clustering analysis. Lnc-CCNY-1 was selected as the key lncRNA. GSVA analysis showed that lnc-CCNY-1 was negatively associated with peroxisome proliferator-activated receptor (PPAR) signaling pathway and positively correlated with CELL cycle pathway. Conclusion. Two EMT-related lncRNA prognostic models of OS and RFS were constructed to discriminate patients and predict prognosis of HCC. EMT-related lncRNAs may play a role on prognosis of HCC by influencing the immune microenvironment. Lnc-CCNY-1 was selected as the key EMT-related lncRNA for further exploration.

Efficacy Analysis of Multidisciplinary Treatment for Wilm’s Tumor in Single Center

Objective: To analyze the efficacy of multidisciplinary treatment (MDT) for Wilm’s tumor (WT) in Kunming Children’s Hospital, and investigate the risk factors affecting the prognosis of WT.Method: The clinic-pathological data were collected and analyzed in patients with unilateral WT treated in Kunming Children's Hospital from January 2017 to July 2021. Research objects were selected according to inclusion criteria and exclusion criteria. The risk factors and independent risk factors that affect the prognosis of patients with WT were determined by Kaplan-Meier survival analysis and Cox proportional hazards model, respectively. Outcome: A total of 68 children were included in this study, and the 5-year overall survival (OS) rate was 92.65%. Kaplan-Meier survival analysis results showed that ethnicity (P=0.020), the tumor volume of resection (P=0.001), histological type (P<0.001), and postoperative recurrence (P<0.001) were the factors affecting the prognosis of children with WT. The results of the Cox proportional hazards model showed that only the histological type (P=0.028) was the independent risk factor for the prognosis of WT.Conclusion: The efficacy of MDT for WT was satisfying. The histological type has important predictive value for the prognosis of WT, and the patient with unfavorable histology has a poor prognosis.

The Prognostic Value of the Prognostic Nutritional Index in Operable High-Grade Glioma Patients and the Establishment of a Nomogram

BackgroundStudies confirmed the predictive value of the prognostic nutrition index (PNI) in many malignant tumors. However, it did not reach a consensus in glioma. Therefore, this study investigated the prognostic value of preoperative PNI in operable high-grade glioma and established a nomogram.MethodsClinical data of high-grade glioma patients were retrospectively analyzed. The primary endpoint was overall survival (OS). Survival analysis was conducted by the Kaplan–Meier method, log-rank test, and Cox regression analysis. A nomogram was established. The prediction effect of the nomogram covering PNI was verified by area under the curve (AUC).ResultsA total of 91 operable high-grade glioma patients were included. Kaplan–Meier analysis showed that among grade IV gliomas (n = 55), patients with higher PNI (&gt;44) showed a trend of OS benefit (p = 0.138). In grade III glioma (n = 36), patients with higher PNI (&gt;47) had longer OS (p = 0.023). However, the intersecting Kaplan–Meier curve suggested that there may be some confounding factors. Cox regression analysis showed that higher PNI was an independent prognostic factor for grade IV glioma (HR = 0.388, p = 0.040). In grade III glioma, there was no statistically relationship between PNI levels and prognosis. When evaluating the prognostic ability of PNI alone by ROC, the AUC in grade III and IV gliomas was low, indicating that PNI alone had poor predictive power for OS. Interestingly, we found that the nomogram including preoperative PNI, age, extent of resection, number of gliomas, and MGMT methylation status could predict the prognosis of patients with grade IV glioma well.ConclusionThe PNI level before surgery was an independent prognostic factor for patients with grade IV glioma. The nomogram covering PNI in patients with grade IV glioma also proved the value of PNI. However, the value of PNI in grade III glioma needs to be further evaluated. More prospective studies are needed to verify this conclusion.

Prediction of distant metastasis of spinal and pelvic osteosarcoma by constructing and validating nomogram:a retrospective study based on SEER database

Background:Spinal and pelvic osteosarcoma is a rare type of all osteosarcomas,and distant metastasis is an important factor for poor prognosis of this disease. There are no similar studies on prediction of distant metastasis of spinal and pelvic osteosarcoma. We aim to construct and validate a nomogram to predict the risk of distant metastasis of spinal and pelvic osteosarcoma.Methods:We collected the data on patients with spinal and pelvic osteosarcoma from the Surveillance, Epidemiology, and End Results(SEER) database retrospectively. The Kaplan-Meier curve was used to compare differences in survival time between patients with metastasis and non-metastasis. Total patients were randomly divided into training cohort and validation cohort. The risk factor of distant metastasis were identified via the least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic analysis. The nomogram we constructed were validated internally and externally by C-index, calibration curves,receiver operating characteristic(ROC) curve and Decision curve analysis (DCA).Results:The Kaplan-Meier curve showed that the survival time of non-metastatic patients was longer than that of metastatic patients(P＜0.001).All patients(n=358) were divided into training cohort(n=269) and validation cohort(n=89).The LASSO regression selected five meaningful variables in the training cohort. The multivariate logistic regression analysis demonstrated that surgery(yes,OR=0.175, 95%CI=0.095-0.321,p=0.000) was the independent risk factors for distant metastasis of patients with spinal and pelvic osteosarcoma. The C-index and calibration curves showed the good agreement between the predicted results and the actual results. The area under the receiver operating characteristic curve(AUC) values were 0.748(95%CI=0.687-0.817) and 0.758(95%CI=0.631-0.868) in the training and validation cohorts respectively. The DCA showed that the nomogram has a good clinical usefulness and net benefit.Conclusion:No surgery is the independent risk factor of distant metastasis of spinal and pelvic osteosarcoma. The nomogram we constructed to predict the probability of distant metastasis of patients with spinal and pelvic osteosarcoma is reliable and effective by internal and external verification.

Irradiation of the Subventricular Zone and Subgranular Zone in High- and Low-Grade Glioma Patients: an Atlas-based Analysis on Overall Survival

Background Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p&lt;0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p&lt;0.001; multivariate: 1.055/Gy, p&lt;0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (&gt;30.33 Gy) vs 14.0 months (&lt;30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (&gt;29.11 Gy) vs 15.5 months (&lt;29.11 Gy) median OS, p&lt;0.001). No correlations between dose and OS were found for LGG patients. Conclusion Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Early Hepatocellular Carcinoma: A Study Based on SEER Database

Background: Primary liver cancer is a common malignant tumor primarily represented by hepatocellular carcinoma (HCC). The number of elderly patients with early HCC is increasing, and older age is related to a worse prognosis. However, an accurate predictive model for the prognosis of these patients is still lacking.Methods: Data of eligible elderly patients with early HCC in Surveillance, Epidemiology, and End Results database from 2010 to 2016 were downloaded. Patients from 2010 to 2015 were randomly assigned to the training cohort (n = 1093) and validation cohort (n = 461). Patients' data in 2016 (n = 431) was used for external validation. Independent prognostic factors were obtained using univariate and multivariate analyses. Based on these factors, a cancer-specific survival (CSS) nomogram was constructed. The predictive performance and clinical practicability of our nomogram were validated. According to the risk scores of our nomogram, patients were divided into low-, intermediate-, and high-risk groups. A survival analysis was performed using Kaplan–Meier curves and log-rank tests.Results: Age, race, T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent predictors for CSS and thus were included in our nomogram. In the training cohort and validation cohort, the concordance indices (C-indices) of our nomogram were 0.739 (95% CI: 0.714–0.764) and 0.756 (95% CI: 0.719–0.793), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves (AUCs) showed similar results. Calibration curves revealed high consistency between observations and predictions. In external validation cohort, C-index (0.802, 95%CI: 0.778–0.826) and calibration curves also revealed high consistency between observations and predictions. Compared with the TNM stage, nomogram-related decision curve analysis (DCA) curves indicated better clinical practicability. Kaplan–Meier curves revealed that CSS significantly differed among the three different risk groups. In addition, an online prediction tool for CSS was developed.Conclusions: A web-based prediction model for CSS of elderly patients with early HCC was constructed and validated, and it may be helpful for the prognostic evaluation, therapeutic strategy selection, and follow-up management of these patients.