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2021 ◽  
Hong Wu ◽  
haiqin Feng ◽  
Xiaoli Miao ◽  
jiancai Ma ◽  
Cairu Liu ◽  

Abstract Background: Endometrial cancer (EC) is one of the most common malignant tumor in the female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic model and effective biomarkers for early diagnosis is important to reduce the mortality rate. Methods: We downloaded the RNA-sequencing data and clinical information from the TCGA database. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed genes (DEGs). A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related LNM related genes signature. Subsequently, a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic significance of the risk model and key gene was validated in vitro. Results: In total, 89 LRGs were identified. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan–Meier curve indicated that patients in the low-risk group had considerably better OS (P = 3.583e−08). The area under the curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival verification performed in three subgroups from the nomogram demonstrated the validity of the model. The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively. Conclusions: Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients. By detecting the mutation of the risk signature, clinicians can accurately treat patients with targeted therapy, thereby improving their survival rate.

2021 ◽  
Vol 11 ◽  
Zhenming Tang ◽  
Shuhui Zhang ◽  
Zhougui Ling

BackgroundTherapeutic outcomes of osteosarcoma treatment have not significantly improved in several decades. Therefore, strong prognostic biomarkers are urgently needed.MethodsWe first extracted the tRNA-derived small RNA (tsRNA) expression profiles of osteosarcoma from the GEO database. Then, we performed a unique module analysis and use the LASSO-Cox model to select survival-associated tsRNAs. Model effectiveness was further verified using an independent validation dataset. Target genes with selected tsRNAs were predicted using RNAhybrid.ResultsA LASSO-Cox model was established to select six prognostic tsRNA biomarkers: tRF-33-6SXMSL73VL4YDN, tRF-32-6SXMSL73VL4YK, tRF-32-M1M3WD8S746D2, tRF-35-RPM830MMUKLY5Z, tRF-33-K768WP9N1EWJDW, and tRF-32-MIF91SS2P46I3. We developed a prognostic panel for osteosarcoma patients concerning their overall survival by high-low risk. Patients with a low-risk profile had improved survival rates in training and validation dataset.ConclusionsThe suggested prognostic panel can be utilized as a reliable biomarker to predict osteosarcoma patient survival rates.

2021 ◽  
Wang-Ying Dai ◽  
Bin Wang ◽  
Jian-Yi Li ◽  
Jun-Cheng Zhu ◽  
Zong-ping Luo

Abstract Background: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long non-coding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They target mRNA through transcription or post-transcription, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators.Objective: The objective of the present study was to identify immune-related lncRNAs associated with the tumor microenvironment that can be used to predict soft tissue sarcomas.Methods: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from. The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and co-expression analysis. The Cox regression model and Kaplan–Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. Lastly, we constructed an mRNA-lncRNA network by Cytoscape software.Results: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan–Meier(K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established.Conclusion: The results indicate that seven OS- and five DFS-related lncRNAs are correlated with the prognosis of soft tissue sarcoma.

2021 ◽  
Vol 12 ◽  
Zijin Xiang ◽  
Xueru Chen ◽  
Qiaoli Lv ◽  
Xiangdong Peng

BackgroundAs immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients.MethodsBy downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups.ResultsA novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes.ConclusionThe risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 540
Alberto Altafini ◽  
Paola Roncada ◽  
Alessandro Guerrini ◽  
Gaetan Minkoumba Sonfack ◽  
Giorgio Fedrizzi ◽  

The detection of Ochratoxin A (OTA) in the milk of ruminants occurs infrequently and at low levels, but its occurrence may be higher in dairy products such as cheese. The aim of this study was to investigate the presence of OTA in cheeses purchased in the metropolitan city of Bologna (Italy) and the surrounding area. For the analysis, a LC-MS/MS method with a limit of quantification (LOQ) of 1 µg/kg was used. OTA was detected in seven out of 51 samples of grated hard cheese (concentration range 1.3–22.4 µg/kg), while it was not found in the 33 cheeses of other types which were also analysed. These data show a low risk of OTA contamination for almost all types of cheese analysed. To improve the safety of cheese marketed in grated form, more regulations on cheese rind, which is the part most susceptible to OTA-producing moulds, should be implemented or, alternatively, producers should consider not using the rind as row material for grated cheese. It would be interesting to continue these investigations particularly on grated hard cheeses to have more data to update the risk assessment of OTA in cheese, as also suggested by EFSA in its 2020 scientific opinion on OTA.

2021 ◽  
Martin Bulla ◽  
Christina Muck ◽  
Daniela Tritscher ◽  
Bart Kempenaers

Biparental care requires coordination between parents. Such coordination might prove difficult if opportunities to communicate are scarce, which might have led to the evolution of elaborate and noisy nest relief rituals in species facing a low risk of predation. However, whether such conspicuous rituals also evolved in species that avoid predation by relying on crypsis remains unclear. Here, we used a continuous monitoring system to describe nest relief behavior during incubation in an Arctic-breeding shorebird with passive nest defense, the semipalmated sandpiper (Calidris pusilla). We then explored whether nest relief behavior provides information about parental cooperation and predicts incubation effort. We found that incubating parents vocalized twice as much before the arrival of their partner than during other times of incubation. In 75% of nest reliefs, the incubating parent left the nest only after its partner had returned and initiated the nest relief. In these cases, exchanges were quick (25s, median) and shortened over the incubation period by 0.1 – 1.4s per day (95%CI), suggesting that parents became more synchronized. However, nest reliefs were not cryptic. In 90% of nest reliefs, at least one parent vocalized, and in 20% of nest reliefs, the incubating parent left the nest only after its returning partner called instantaneously. In 30% of cases, the returning parent initiated the nest relief with a call; in 39% of these cases, the incubating partner replied. If the partner replied, the next off-nest bout was 1 – 4hr (95%CI) longer than when the partner did not reply, which corresponds to an 8 – 45% increase. Our results indicate that incubating semipalmated sandpipers, which rely on crypsis to avoid nest predation, have quick but acoustically conspicuous nest reliefs. Our results also suggest that vocalizations during nest reliefs may be important for the division of parental duties.

2021 ◽  
Vol 19 (1) ◽  
Youyin Tang ◽  
Tao Zhang ◽  
Xianghong Zhou ◽  
Yunuo Zhao ◽  
Hanyue Xu ◽  

Abstract Background Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. Methods In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. Results A total of 101patients (mean age, 58.2 years old; range 36–79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). Conclusions This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3857
Pilar Mur ◽  
Nuria Bonifaci ◽  
Anna Díez-Villanueva ◽  
Elisabet Munté ◽  
Maria Henar Alonso ◽  

A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.

Jianhong Chen ◽  
Kun Yu ◽  
Wenhao Wang

Key exposure is very harmful to a cryptographic system. To decrease the loss from the deputy signing key vulnerability in identity-based proxy signature systems, we propose the method of key protected deputy signature (IBKPDS) using the method of parallel key insulation. The proposed IBKPDS is based on identities and is shown to be secure with the cryptographic proof. In the proof, there is no random oracle. In an IBKPPS crypto-system, a user stores his short-lived deputy signing key by himself and saves two long-lived keys in two heavily guarded boxes respectively. The derived IBKPDS cryptographic system is heavily key-separated. A thief who wants to obtain crucial information can not corrupt the IBKPDS when he get only one long-lived key. In addition, the user can change the short-lived deputy signing keys frequently at low risk.

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