scholarly journals Identification and Validation of DEPDC1B as an Independent Early Diagnostic and Prognostic Biomarker in Liver Hepatocellular Carcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyan Fan ◽  
Junye Wen ◽  
Lei Bao ◽  
Fei Gao ◽  
You Li ◽  
...  

Liver hepatocellular carcinoma (LIHC) is one of the most lethal tumors worldwide, and while its detailed mechanism of occurrence remains unclear, an early diagnosis of LIHC could significantly improve the 5-years survival of LIHC patients. It is therefore imperative to explore novel molecular markers for the early diagnosis and to develop efficient therapies for LIHC patients. Currently, DEPDC1B has been reported to participate in the regulation of cell mitosis, transcription, and tumorigenesis. To explore the valuable diagnostic and prognostic markers for LIHC and further elucidate the mechanisms underlying DEPDC1B-related LIHC, numerous databases, such as Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter, and The Cancer Genome Atlas (TCGA) were employed to determine the association between the expression of DEPDC1B and prognosis in LIHC patients. Generally, the DEPDC1B mRNA level was highly expressed in LIHC tissues, compared with that in normal tissues (p < 0.01). High DEPDC1B expression was associated with poor overall survival (OS) in LIHC patients, especially in stage II, IV, and grade I, II, III patients (all p < 0.05). The univariate and multivariate Cox regression analysis showed that DEPDC1B was an independent risk factor for OS among LIHC patients (HR = 1.3, 95% CI: 1.08–1.6, p = 0.007). In addition, the protein expression of DEPDC1B was validated using Human Protein Atlas database. Furthermore, the expression of DEPDC1B was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) assay using five pairs of matched LIHC tissues and their adjacent noncancerous tissues. The KEGG pathway analysis indicated that high expression of DEPDC1B may be associated with several signaling pathways, such as MAPK signaling, the regulation of actin cytoskeleton, p53 signaling, and the Wnt signaling pathways. Furthermore, high DEPDC1B expression may be significantly associated with various cancers. Conclusively, DEPDC1B may be an independent risk factor for OS among LIHC cancer patients and may be used as an early diagnostic marker in patients with LIHC.

2013 ◽  
Vol 19 (1) ◽  
pp. 51-56
Author(s):  
Andra-Iulia Suceveanu ◽  
Laura Mazilu ◽  
F. Voinea ◽  
A.P Suceveanu ◽  
Irinel Raluca Parepa ◽  
...  

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies with increasing incidence in developed countries. Epidemiological studies show that the cause of new discovered HCC cases remains unclear in 15%-50% of cases. Obesity and the subsequent/ underlying nonalcoholic fatty liver disease (NAFLD) can be responsible for most of these cases. The aim of our study was to estimate the risk of HCC in obese patients diagnosed with NAFLD, without clinical or imagistic features of liver cirrhosis, in order to see if HCC can develop in fatty liver in the absence of cirrhosis. Patients with regular/daily alcohol consumption or diagnosed with liver viral infections were excluded. We studied 214 obese patients with NAFLD over a period of 5 years. We evaluated all patients using abdominal ultrasound and serum alpha-fetoprotein every 6 month, in order to detect the HCC occurrence. Kaplan-Meier analysis estimated the cumulative incidence of HCC. Univariate and multivariate Cox regression analysis were used to assess associations between HCC and obesity. The median follow-up was 4.3 years. During the study period, 16 from 118 cirrhotic NFLAD patients (13.5%) and 12 from 96 non-cirrhotic NAFLD patients (12.5 %) developed HCC (p = 0.07, ns). The cumulative incidence of HCC was found to be 2.9% in obese patients with NAFLD-cirrhosis, compared with 2.2% in obese patients without cirrhosis (p = 0.09, ns). Multivariate regression analysis revealed that older age (p = 0.04) was independent variable associated with development of HCC in patients with/without NAFLDcirrhosis. Obesity seems to be an independent risk factor for HCC occurrence, regardless the presence of mild or advanced liver fibrosis in NAFLD patients.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Siqing Wang ◽  
Aiya Qin ◽  
Gaiqin Pei ◽  
Zheng Jiang ◽  
Lingqiu Dong ◽  
...  

Abstract Background Whether cigarette smoking is associated with the progression of immunoglobulin A nephropathy (IgAN) remains uncertain; therefore, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN. Methods We divided 1239 IgAN patients from West China Hospital of Sichuan University who met the inclusion criteria into smoker (current or former) and non-smoker groups. The endpoint was end-stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or undergoing renal replacement treatment) and/or eGFR decreased by > 50%. Kaplan–Meier, correlation, logistic regression and Cox proportional hazards analyses were performed. The association between cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis. Results During the mean follow-up period of 61 months, 19% (40/209) of the smoker group and 11% (110/1030) of the non-smoker group reached the study endpoint (p < 0.001). Multivariate Cox regression analysis revealed that cigarette smoking (hazard ratio (HR) = 1.58; p = 0.043) was an independent risk factor predicting poor renal progression in IgAN, and that IgAN patients with chronic kidney disease (CKD) stage 3–4 were more susceptible to cigarette smoking (p < 0.001). After propensity score matching (PSM), a significant correlation between cigarette smoking and renal outcomes in IgAN patients was seen. Furthermore, Spearman’s correlation test revealed that smoking dose was negatively correlated with eGFR (r = 0.141; p < 0.001) and positively related with proteinuria (r = 0.096; p = 0.001). Conclusions Cigarette smoking is an independent risk factor for IgAN progression, especially for advanced patients.


2021 ◽  
Author(s):  
Desheng Cai ◽  
Zixin Wang ◽  
Yu Fan ◽  
Lin Cai ◽  
Kan Gong

Abstract Background: Tertiary Gleason pattern 5 (TGP5) was found to be prognostic in prostate cancer (PCa) after radical prostatectomy (RP), but related data from China was rare. Our study was aimed at finding out the effect of TGP5 on PCa with Gleason score (GS) 7 and supplementing data from China in this field.Methods: A total of 229 cases met with inclusion criteria during Jan. 2014 to Dec. 2018 were reviewed. Cases were divided into GS 7 without TGP5 and GS 7 with TGP5. We compared age at diagnosis, preoperative PSA level, prostate volume, PSA density (PSAD), GS variation, clinical T staging, pathological T staging, T staging variation, extra-prostatic extension (EPE), positive surgical margin (PSM) and seminal vesicle invasion (SVI) between the groups. Effects of TGP5 on prognosis of PCa with GS 7 were evaluated using biochemical recurrence (BCR) as the primary end point.Results: TGP5 was related to higher PSM rate (P=0.001) and BCR rate (P=0.009) but not related to higher preoperative PSA level, larger prostate volume, higher PSAD, GS upgrade, poorer clinical/pathological T staging, T upstaging, EPE and SVI (all P>0.05). The median follow-up time was 24 months (interquartile range 17.5-45.5). TGP5 was an independent risk factor to PCa with GS 7 after RP using Kaplan-Meier log-rank test (P=0.018). Both univariable and multivariable cox-regression analysis pointed out that TGP5 increased the incidence of BCR in PCa with GS 7 (P<0.05). Stratified analyses were also done.Conclusion: TGP5 is an independent risk factor predicting of BCR after RP in PCa with GS 7 from China. TGP5 is related to higher PSM rate and BCR incidence. It is time to renew the contemporary Grading Group system with the consideration of TGP.


2021 ◽  
Author(s):  
Meimei Liu ◽  
Qiong Fang ◽  
Yanping Huang ◽  
Jin Zhou ◽  
Qi Wang

Abstract Background: Extensive research has revealed that costimulatory molecules play central roles in mounting anti-tumor immune responses and long non‐coding RNA (lncRNA) is an important regulatory factor in the development of various cancers. However, their roles in liver hepatocellular carcinoma (HCC) remain unexplored. In this study, we aimed to explore costimulatory molecule-related lncRNAs in HCC and construct a prognostic signature to predict prognosis and improve clinical outcomes with HCC patients.Methods: The data we used for bioinformatics analysis were downloaded from The Cancer Genome Atlas database. Costimulatory molecules were obtained from the known literature. The R software, SPSS and GraphPad Prism were used for mapping and statistical analysis.Results: A five costimulatory molecule-related lncRNAs based risk model was initially constructed through lasso and Cox regression analysis. Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in HCC. Samples in high- and low-risk groups exhibited significantly different in gene set enrichment analysis and immune infiltration analysis. Importantly, we found that the AC099850.3 were significantly related to cell proliferation in HCC according to the colony formation and CCK8 assays.Conclusion: In summary, we first identified and validated a novel costimulatory molecule-related survival model and we found that AC099850.3 is closely associated with clinical stage and could remarkably facilitate cell proliferation in HCC, making it potential to be a novel therapeutic target.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Chen ◽  
Yan Qun Liu ◽  
Shi Xiang Qiu ◽  
Ya Li ◽  
Ning Jun Yu ◽  
...  

Abstract Backgrounds Liver hepatocellular carcinoma (HCC) is one of the most malignant tumors, of which prognosis is unsatisfactory in most cases and metastatic of HCC often results in poor prognosis. In this study, we aimed to construct a metastasis- related mRNAs prognostic model to increase the accuracy of prediction of HCC prognosis. Methods Three hundred seventy-four HCC samples and 50 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database, involving transcriptomic and clinical data. Metastatic-related genes were acquired from HCMBD website at the same time. Two hundred thirty-three samples were randomly divided into train dataset and test dataset with a proportion of 1:1 by using caret package in R. Kaplan-Meier method and univariate Cox regression analysis and lasso regression analysis were performed to obtain metastasis-related mRNAs which played significant roles in prognosis. Then, using multivariate Cox regression analysis, a prognostic prediction model was established. Transcriptome and clinical data were combined to construct a prognostic model and a nomogram for OS evaluation. Functional enrichment in high- and low-risk groups were also analyzed by GSEA. An entire set based on The International Cancer Genome Consortium(ICGC) database was also applied to verify the model. The expression levels of SLC2A1, CDCA8, ATG10 and HOXD9 are higher in tumor samples and lower in normal tissue samples. The expression of TPM1 in clinical sample tissues is just the opposite. Results One thousand eight hundred ninety-five metastasis-related mRNAs were screened and 6 mRNAs were associated with prognosis. The overall survival (OS)-related prognostic model based on 5 MRGs (TPM1,SLC2A1, CDCA8, ATG10 and HOXD9) was significantly stratified HCC patients into high- and low-risk groups. The AUC values of the 5-gene prognostic signature at 1 year, 2 years, and 3 years were 0.786,0.786 and 0.777. A risk score based on the signature was a significantly independent prognostic factor (HR = 1.434; 95%CI = 1.275–1.612; P < 0.001) for HCC patients. A nomogram which incorporated the 5-gene signature and clinical features was also built for prognostic prediction. GSEA results that low- and high-risk group had an obviously difference in part of pathways. The value of this model was validated in test dataset and ICGC database. Conclusion Metastasis-related mRNAs prognostic model was verified that it had a predictable value on the prognosis of HCC, which could be helpful for gene targeted therapy.


2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jun C. Takahashi ◽  
Takeshi Funaki ◽  
Kiyohiro Houkin ◽  
Satoshi Kuroda ◽  
Miki Fujimura ◽  
...  

OBJECTIVEHere, the authors aimed to determine whether the presence of cerebral hemodynamic failure predicts subsequent bleeding attacks and how it correlates with the effect of direct bypass surgery in hemorrhagic moyamoya disease.METHODSData from the Japanese Adult Moyamoya (JAM) Trial were used in this study: 158 hemispheres in 79 patients. A newly formed expert panel evaluated the SPECT results submitted at trial enrollment and classified the cortical hemodynamic state of the middle cerebral artery territory of each hemisphere into one of the following three groups: SPECT stage (SS) 0 as normal, SS1 as decreased cerebrovascular reserve (CVR), and SS2 as decreased CVR with decreased baseline blood flow. In the nonsurgical cohort of the JAM Trial, the subsequent hemorrhage rate during the 5-year follow-up was compared between the SS0 (hemodynamic failure negative) and SS1+2 (hemodynamic failure positive) groups. The effect of direct or combined direct/indirect bypass surgery on hemorrhage prevention was examined in each subgroup.RESULTSThe hemodynamic grade was SS0 in 59 (37.3%) hemispheres, SS1 in 87 (55.1%), and SS2 in 12 (7.6%). In the nonsurgical cohort, subsequent hemorrhage rates in the SS0 and SS1+2 groups were 12 cases per 1000 person-years and 67 cases per 1000 person-years, respectively. Kaplan-Meier analysis revealed that hemorrhagic events were significantly more common in the SS1+2 group (p = 0.019, log-rank test). Cox regression analysis showed that hemodynamic failure was an independent risk factor for subsequent hemorrhage (HR 5.37, 95% CI 1.07–27.02). In the SS1+2 subgroup, bypass surgery significantly suppressed hemorrhagic events during 5 years (p = 0.001, HR 0.16, 95% CI 0.04–0.57), with no significant effect in the SS0 group (p = 0.655, HR 1.56, 95% CI 0.22–11.10). Examination of effect modification revealed that the effect of surgery tended to differ nonsignificantly between these two subgroups (p = 0.056).CONCLUSIONSHemodynamic failure is an independent risk factor for subsequent hemorrhage in hemorrhagic moyamoya disease. Direct bypass surgery showed a significant preventive effect in the hemodynamically impaired hemispheres. Thus, hemodynamic failure, as well as previously proposed factors such as choroidal anastomosis, should be considered for the surgical indication in hemorrhagic moyamoya disease.Clinical trial registration no.: C000000166 (umin.ac.jp)


Author(s):  
Chunxia Zhou ◽  
Jing Sun ◽  
Fengqin Xu ◽  
Shanping Jiang

Aims: This retrospective study aimed to evaluate the impact of eosinopenia on 28-day mortality in Staphylococcus aureus bloodstream infection (SABSI).  Methods:  A retrospective study was designed to evaluate the impact of eosinopenia on 28-day mortality in SABSI. Results: Patients who were ≥16 years old with SABSI at Sun Yat-Sen Memorial Hospital between January 1st 2014 and December 31st 2018 were included. The overall 28-day mortality of all patients was 14.3% (44 out of 307). Patients with eosinopenia in the onset of SABSI had a significantly higher 28-day mortality than those without eosinopenia (22.4% vs 6.5%; P<0.01). For patients who developed SABSI after the first 48 hours in the hospital, eosinophils decreased significantly from the baseline (P<0.01). Kaplan–Meier survival curve showed that patients with eosinopenia had a lower survival rate than those without eosinopenia (P<0.01). Multivariate Cox regression analysis revealed that eosinophils in the onset of SABSI were associated independently with 28-day mortality (hazard ratio [HR], 2.84; 95% confidence interval [CI], 1.36–5.91; P<0.01). Conclusion: Eosinopenia associated with infection might be an independent risk factor for 28-day mortality in SABSI.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Zhu ◽  
Yanlei Zheng ◽  
Ronghua Hu ◽  
Chenchen Hu

Recent studies have found that cytoskeleton-associated protein 2 like (CKAP2L), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and CKAP2L expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. CKAP2L expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of CKAP2L was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that CKAP2L can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that CKAP2L may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on CKAP2L were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.


2021 ◽  
Author(s):  
chao chen ◽  
ShiXiang Qiu ◽  
Ya Li ◽  
YanQun Liu ◽  
Kang Liu ◽  
...  

Abstract Backgrounds: Liver hepatocellular carcinoma (LIHC) is one of the most malignant tumors, of which prognosis is unsatisfactory in most cases and metastatic of LIHC often results in poor prognosis. In this study, we aimed to construct a metastasis- related mRNAs prognostic model to increase the accuracy of prediction of LIHC prognosis.Methods: 374 LIHC samples and 50 normal samples were downloaded from TCGA database, involving transcriptomic and clinical data. Metastatic-related genes were acquired from HCMBD website at the same time. 343 samples were randomly divided into train dataset and test dataset with a proportion of 1:1 by using caret package in R. Kaplan-Meier method and univariate Cox regression analysis and lasso regression analysis were performed to obtain metastasis-related mRNAs which played significant roles in prognosis. Then, using multivariate Cox regression analysis, a prognostic prediction model was established. Transcriptome and clinical data were combined to construct a prognostic model and a nomogram for OS evaluation. Functional enrichment in high- and low-risk groups were also analyzed by GSEA. An entire set was applied to verify the model.Results: 1895 metastasis-related mRNAs were screened and 8mRNAs were associated with prognosis. The overall survival (OS)-related prognostic model which was constructed based on 4 MRGs (MMP1, SPP1, STC2, CDCA8) significantly stratified LIHC patients into high- and low-risk groups. The AUC values of the 4-gene prognostic signature at 1 year, 2 years, and 3 years were 0.807,0.729 and 0.673. A risk score based on the signature was a significantly independent prognostic factor (HR=1.295; 95%CI=1.167-1.436; P<0.001) for LIHC patients. A nomogram which incorporated the 4-gene signature and clinical features was also built for prognostic prediction. GSEA results that low- and high-risk group had an obviously difference in part of pathways. The value of this model was validated in test dataset and entire set.Conclusion: Metastasis-related mRNAs prognostic model was verified that it had a predictable value on the prognosis of LIHC, which could be helpful for gene targeted therapy.


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