scholarly journals NMB as a Novel Prognostic Biomarker in Colorectal Cancer Correlating with Immune Infiltrates

Author(s):  
Jiaxin Fan ◽  
Chaowei Liang ◽  
Jiajia Wang ◽  
Chaojie Liang ◽  
Jiansheng Guo

Abstract Background:Neuromedin B(NMB) is associated with the occurrence and development of a variety of cancers, However, the role of NMB in colorectal cancer is lacking in further studies.Methods:Transcriptome data and clinical data of CRC were downloaded and analyzed from the TCGA database and GEO database to study the differential expression of NMB. We analyzed the relationship between NMB expression and survival in patients with colorectal cancer using 8 public datasets from the Gene Expression Integration (GEO) database and the TCGA database. Meta-analysis was performed on the analysis results of TCGA and GEO data to determine the role of NMB in CRC. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of NMB in predicting survival rate in CRC patients. Wilcox. Test and Kruskal. Tests were used to study the relationship between clinicopathological features and the expression of NMB. Cox regression analysis was used to analyze the effect of NMB expression on survival. Gene collection enrichment analysis (GSEA) was performed using the TCGA database to screen the signaling pathway regulated by NMB. The Linkedomics platform was used to identify NMB co-expressed genes and explore the potential mechanisms of NMB mediation. Tumor Immune Estimation Resource (TIMER) site database was used to analyze the relationship between NMB expression level and immune infiltration. Related genes were identified by co-expression analysis, and four genes (NDUFB10, SERF2, DPP7, and NAPRT) were screened out as a prognostic signature. The relationship between risk score and OS were studied to explore the predictive value of risk score for CRC. Nomogram was constructed to predict 1 - and 3-year survival in colorectal cancer patients.Results:NMB was highly expressed in colorectal cancer, suggested a poor prognosis. The ROC curve proved that NMB had a high accuracy in predicting the survival rate of CRC patients. Multivariate regression analysis demonstrated that NMB was an independent predictor of survival in patients with CRC.GSEA identified the pathways involved in NMB regulation, including the P53 Signaling pathway, VEGF Signaling pathway, JAK-STAT Signaling pathway, MAPK Signaling pathway,mTOR Signaling pathway, TGF-BETA Signaling pathway, and WNT Signaling pathway, etc. Then,6512 co-expressed genes were identified through the Linkedomics Platform to investigate the potential mechanisms of NMB regulation, including Hepatocellular carcinoma cell cycle, EGF/EGFR Signaling Pathway, VEGFA-VEGFR2 Signaling Pathway, etc. We also conclude that NMB is correlated with T cells CD8, T cells CD4 memory resting, Macrophages M0. Different mutational forms of NMB were associated with the immune infiltration of 6 leukocytes. We determined the relationship between NMB and immune marker sets in colorectal cancer, such as CCR7, CD3E, CTLA4, HAVCR2, HLA-DPB1. The predictive ability of the risk score was significantly better than that of T, N, and M stages. A new nomogram for predicting the 1-year and 3-year OS of CRC patients was constructed, showing good reliability and accuracy for improved treatment decisions. In addition, NMB may contribute to drug resistance in CRC.Conclusion:NMB is highly expressed in CRC and provides a potential biomarker for the diagnosis and prognosis of CRC.

2021 ◽  
Author(s):  
Fang Liu ◽  
Fengyihuan Fu ◽  
Yuqiang Nie

Abstract Background: LINC00634 is highly expressed in esophageal cancer, and its depletion can suppress the viability and induce the apoptosis of esophageal cancer cells. However, there is a lack of studies that examine the relationship between LINC00634 expression and the clinicopathological features, survival outcomes, prognostic factors and tumor immune cell infiltration of colorectal carcinoma (CRC) patients.Objective: We aim at investigating the role of LINC00634 in colorectal carcinoma.Methods: We obtained data from the TCGA (The Cancer Genome Atlas) public database, GTEx (Genotype-Tissue Expression) database and clinical samples. Wilcoxon rank-sum test, Kruskal-Wallis test and logistic regression analysis were employed to assess the relationship between LINC00634 expression and the clinicopathological characteristics of CRC patients. Receiver operating characteristic (ROC) curve was constructed to evaluate the ability of LINC00634 for distinguishing between CRC patients and normal subjects based on the area under the curve (AUC) score. Univariate and multivariate analyses were conducted to evaluate the association between prognostic factors and survival outcomes. Kaplan-Meier curves and Cox regression analysis were employed to determine the contribution of LINC00634 expression to the prognosis of colorectal carcinoma patients. Immune infiltration analysis and Gene Set Enrichment Analysis (GSEA) were conducted to identify the significantly involved functions of LINC00634. Finally, a nomogram was constructed for internal verification based on the Cox regression data.Results: The expression of LINC00634 was upregulated in CRC patients, and markedly associated with N stage, residual tumor, pathological stage, and overall survival (OS) event. ROC curve showed that LINC00634 had strong diagnostic and prognostic abilities (AUC=0.74). The high expression of LINC00634 could predict poor disease specific survival (DSS; P=0.008) and poor overroll survival (OS;P<0.01). The expression of LINC00634 was independently associated with OS in CRC patients (P=0.019). GSEA and immune infiltration analysis demonstrated that LINC00634 expression was involved in gene transcription, epigenetic regulation and the functions of certain types of immune infiltrating cells. The c-index of the nomogram was 0.772 (95%CI: 0.744-0.799).Conclusions: Our study reveals that LINC00634 can serve as a potential prognostic biomarker for CRC patients.


2021 ◽  
pp. 003693302199424
Author(s):  
Gaoli Liu ◽  
Bicheng Zhang ◽  
Shaowen Zhang ◽  
Haifeng Hu ◽  
TingTing Liu

Aims To search for biochemical indicators that can identify symptomatic patients with COVID-19 whose nucleic acid could turn negative within 14 days, and assess the prognostic value of these biochemical indicators in patients with COVID-19. Patients and methods We collected the clinical data of patients with COVID-19 admitted to our hospital, by using logistic regression analysis and AUC curves, explored the relationship between biochemical indicators and nucleic acid positive duration, the severity of COVID-19, and hospital stay respectively. Results A total of two hundred and thirty-three patients with COVID-19 were enrolled in the study. We found patients whose nucleic acid turned negative within 14 days had lower LDH, CRP and higher ALB ( P < 0.05). ROC curve results indicated that lower LDH, TP, CRP and higher ALB predicted the nucleic acid of patients turned negative within 14 days with statistical significance( P < 0.05), AST, LDH, CRP and PCT predicted the severe COVID-19 with statistical significance, and CRP predicted hospital stay >31days with statistical significance ( P < 0.05). After verification, the probability of nucleic acid turning negative within 14 days in patients with low LDH (<256 U/L), CRP (<44.5 mg/L) and high ALB (>35.8 g/L) was about 4 times higher than that in patients with high LDH, CRP and low ALB ( P < 0.05). Conclusions LDH, CRP and ALB are useful prognostic marker for predicting nucleic acid turn negative within 14 days in symptomatic patients with COVID-19.


Author(s):  
June Won ◽  
J. Lucy Lee

The purpose of this study was to: (a) investigate the actual positions in digital communications; (b) assess the relationship between position-congruity among intended positions (i.e., how a firm desires to be perceived by consumers), actual brand positions, and perceived brand positions (i.e., the perceptions that customers have in their minds); and (c) understand the role of actual positioning (AP) in the positioning process. Multiple methods (one-on-one and focus group interviews, content analysis) were applied to analyze positions. Brand managers, golf consumers, and digital advertisements in Golf Digest magazine were sampled. Content analysis, frequencies and percentages, percentage difference, and regression analysis were performed for all positions for each research brand. The results revealed that: (a) tangibility-based positions (88.5%: great quality, innovation) outnumbered intangibility-based ones (11.5%: tour performance, tradition) in digital AP, (b) there was no positive correlation between the degree of congruence between intended and AP and the degree of congruence between intended and perceived positioning, and (c) the AP mediated between intended and perceived positioning in the brand positioning model. The study provides empirical evidence for the mediating role of AP and suggests modifications to the previous positioning process.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Yan ◽  
Yujuan Gao ◽  
Jingzhi Tong ◽  
Mi Tian ◽  
Jinghong Dai ◽  
...  

BackgroundNumerous studies showed that insulin resistance (IR) was associated with cancer risk. However, few studies investigated the relationship between IR and non-small cell lung cancer (NSCLC). The aim of this study is to explore the association of triglyceride glucose (TyG) index, a simple surrogate marker of IR, with NSCLC risk.Methods791 histologically confirmed NSCLC cases and 787 controls were enrolled in the present study. Fasting blood glucose and triglyceride were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dl) ×fasting glucose (mg/dl)/2]. Logistic regression analysis was performed to estimate the relationship between NSCLC risk and the TyG index.ResultsThe TyG index was significantly higher in patients with NSCLC than that in controls (8.42 ± 0.55 vs 8.00 ± 0.45, P &lt; 0.01). Logistic regression analysis showed that the TyG index (OR = 3.651, 95%CI 2.461–5.417, P &lt; 0.001) was independently associated with NSCLC risk after adjusting for conventional risk factors. In addition, a continuous rise in the incidence of NSCLC was observed along the tertiles of the TyG index (29.4 vs 53.8 vs 67.2%, P &lt; 0.001). However, there were no differences of the TyG index in different pathological or TNM stages. In receiver operating characteristic (ROC) curve analysis, the optimal cut-off level for the TyG index to predict incident NSCLC was 8.18, and the area under the ROC curve (AUROC) was 0.713(95% CI 0.688–0.738).ConclusionsThe TyG index is significantly correlated with NSCLC risk, and it may be suitable as a predictor for NSCLC.


Author(s):  
Wiry Utami

ABSTRACT The research examines the role of time pressure as moderating variable to the relationship between functional value and emotional value on purchase intention on flash sale product. Data for this research were collected by online survey and administered to 150 respondents. The hypothesis testing was conducted using multiple regression analysis and hierarchical regression analysis. Finding of this indicated that functional value and emotional value have positive and significant effect on purchase intention. Time pressure has no negatively moderated the effect of functional value and emotional value on purchase intention. Keywords: functional value, emotional value, time pressure ABSTRAK Penelitian ini menguji peran tekanan waktu sebagai variabel moderasi hubungan antara nilai fungsional dan nilai emosional terhadap niat beli konsumen pada produk flash sale. Data di kumpulkan melalui survey online dengan 150 responden. Pengujian hipotesis dilakukan dengan menggunakan analisis regresi berganda dan analsisi regresi hirarki. Hasil dari penelitian menunjukan bahwa nilai fungsional dan nilai emosional berpengaruh terhadap niat beli. Tekanan waktu tidak memoderasi secara negatif pengaruh nilai fungsional dan nilai emosional terhadap niat beli. Kata Kunci: nilai fungsional, nilai emosional, tekanan waktu


2021 ◽  
Vol 11 ◽  
Author(s):  
Mu-xing Li ◽  
Hang-yan Wang ◽  
Chun-hui Yuan ◽  
Zhao-lai Ma ◽  
Bin Jiang ◽  
...  

IntroductionMacrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases.MethodsWe identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, “key driver” mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed.ResultsWe detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P &lt; 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line.ConclusionsThe nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.


Author(s):  
Lilian Otaye ◽  
Wilson Wong

Purpose – The purpose of this paper is to explore the contours of fairness by showing how different facets of fairness impact three important employee outcomes (job satisfaction, turnover intention and employer advocacy) and examining the mediating role of quality of management and leadership (through perceptions of both senior management and the quality of exchange with immediate supervisors) in attenuating negative impacts of unfairness on these outcomes. The study extends the concept of fairness beyond the traditional focus on organizational justice and models the mediating role of leadership on the relationship between (un)fairness and the three employee-level outcomes in a sample of employees representative of the UK workforce. Design/methodology/approach – Data were obtained from a nationally representative sample of 2,067 employees in the UK. Exploratory factor analysis and then confirmatory factor analysis is used to refine three unfairness factors and address their dimensionality of the unfairness scale and then multiple regression analysis is used to test a fairness-leadership-employee performance outcome model. Findings – Results of multiple regression analysis revealed that both trust in leadership and leader-member exchange partially mediate the relationship between organizational (un)fairness and job satisfaction, advocacy and turnover intention, respectively. Practical implications – The findings highlight the important role that leaders play in influencing the relationship between perception of unfairness and employee outcomes. This has implications for both theory and practice as it suggests that the pattern of inclusion that leaders create through the relationships that they develop with their followers has a significant impact on the relationship between unfairness and the work outcomes. They not only must manage traditional perceptions of justice, but also the assessments employees make about trust in management judgements and the perceived consequences of such judgements. Originality/value – In an environment where perceptions of unfairness are becoming both more endemic but also more complex, the study shows that both senior leaders and immediate supervisors have important agency in managing negative consequences. Through the measurement of satisfaction, turnover intention and employer advocacy it also provides potential links to link fairness into the engagement literature.


2021 ◽  
Vol 27 ◽  
Author(s):  
Qi Zhang ◽  
Yinxin Wu ◽  
Jinlan Chen ◽  
Yuxuan Cai ◽  
Bei Wang ◽  
...  

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Wanjuan Xue ◽  
Yongcheng Liu ◽  
Ningning Xin ◽  
Jiyu Miao ◽  
Juan Du ◽  
...  

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.


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