scholarly journals Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in Tumor Tissues Predicted Worse Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liping Zhuang ◽  
Zongguo Yang ◽  
Zhiqiang Meng

Objective. To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC). Methods. Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients’ survival was analyzed based on TCGA profile. Results. 161 shared upregulated DEGs were identified among GSE45436, GSE55092, GSE60502, and GSE84402 profiles. Cell cycle was the shared pathway/biological process in the gene sets investigation among databases of KEGG, GO, and Reactome. After being validated in GSE17548, 13 genes including BUB1B, CCNA2, CCNB1, CCNE2, CDC20, CDC6, CDC7, CDK1, CDK4, CDKN2A, CHEK1, MAD2L1, and MCM3 in cell cycle pathway were shared in the three databases for enrichment. The expression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 was upregulated in HCC tissues when compared with adjacent normal tissues in 6.67%, 7.5%, 8.06%, 5.56%, and 9.72% of HCC patients, respectively. Overexpression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues accounted for poorer overall survival (OS) and disease-free survival (DFS) in HCC patients (all log rank P < 0.05). BUB1B, CCNB1, CDC7, CDC20, and MCM3 were all overexpressed in HCC patients with neoplasm histologic grade G3-4 compared to those with G1-2 (all P < 0.05). BUB1B, CCNB1, and CDC20 were significantly upregulated in HCC patients with vascular invasion (all P < 0.05). Additionally, levels of BUB1B, CCNB1, CDC7, and CDC20 were significantly higher in HCC patients deceased, recurred, or progressed (all P < 0.05). Conclusion. Correlated with advanced histologic grade and/or vascular invasion, upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues predicted worse OS and DFS in HCC patients. These genes could be novel therapeutic targets for HCC treatment.

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097714
Author(s):  
Liping Zhuang ◽  
Yuan Zhang ◽  
Zhiqiang Meng ◽  
Zongguo Yang

Objective: This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC). Methods: RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset. Results: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml. Conclusions: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1616-1616 ◽  
Author(s):  
Eyal C. Attar ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Michael D. Radmacher ◽  
Susan P. Whitman ◽  
...  

Abstract Abstract 1616 Poster Board I-642 CD74 is a type II integral membrane protein receptor that binds its ligand MIF to induce phosphorylation of the extracellular signal-regulated kinase-1/2 (ERK-1/2) and drive cellular proliferation via nuclear factor-kappa B (NF-kB) activation. CD74 expression has been identified in human solid tumors, and its expression is associated with adverse prognosis in advanced pancreatic cancer. As CD74 is expressed and NF-kB constitutively activated in myeloblasts, we hypothesized that CD74 expression might also be associated with adverse outcome in AML. To investigate the prognostic impact of CD74 expression in the context of other predictive molecular markers in CN-AML, we assessed CD74 expression levels by Affymetrix HG-U133 Plus 2.0 microarray in 102 younger [<60 years (y)] adults with primary CN-AML, treated on the front-line CALGB 19808 trial with an induction regimen containing daunorubicin, cytarabine, etoposide and, in some cases, the inhibitor of multidrug resistance valspodar, and consolidation with autologous stem cell transplantation. Microarray data were analyzed using the Robust Multichip Average method, making use of a GeneAnnot chip definition file, which resulted in a single probe-set measurement for CD74. At diagnosis, CD74 expression, when assessed as a continuous variable, was significantly associated only with extramedullary disease involvement (P=.006) among clinical features, and with none of the molecular prognostic variables tested, including NPM1, WT1, CEBPA, FLT3 (FLT3-ITD and FLT3-TKD) mutations, MLL partial tandem duplication, or differential BAALC and ERG expression levels. Although CD74 expression levels were not associated with achievement of complete remission (CR; 83% vs 81%), higher levels of CD74 were associated with shorter disease-free survival [DFS; P=.046, hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.12-3.08] and with shorter overall survival (OS; P=.02, HR 1.32, CI 1.04-1.67). In multivariable analyses, higher CD74 expression was independently associated with shorter DFS (P=.045, HR 1.98, CI 1.16-3.40), after adjusting for WT1 mutations (P<.001) and FLT3-TKD (P=.04), and shorter OS (P=.01, HR 1.58, CI 1.11-2.25) after adjusting for FLT3-TKD (P=.02), WT1 mutations (P=.007), BAALC expression levels (P=.02), white blood counts (P=.007), and extramedullary involvement (P=.04). As quartiles 2-4 had similar expression levels distinct from the lowest quartile, to display the impact of CD74 expression levels on clinical outcome only, pts were dichotomized into low (the lowest quartile) and high (the top three quartiles) CD74 expressers. The Kaplan-Meier curves for DFS and OS (Figures 1 and 2) are shown below. In conclusion, our study identifies elevated CD74 expression as associated with adverse prognosis in younger CN-AML pts. Since we previously reported that higher CD74 expression was favorably associated with achievement of CR in AML patients receiving chemotherapy plus bortezomib, an inhibitor of the proteasome and NF-kB (Attar et al., Clin Cancer Res, 2008;14:1446-54), it is possible that in future studies elevated CD74 levels can be used not only for prognostication, but also to stratify CN-AML pts to study of bortezomib-containing chemotherapy regimens. Figure 1 Disease free survival Figure 1. Disease free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Jian-Hong Zhong ◽  
Le-Qun Li ◽  
Xin-Ping Ye ◽  
Yang Ke ◽  
Lin Wang ◽  
...  

427 Background: Official guidelines and retrospective studies have different view on the role of hepatic resection (HR) for patients with large (≥5 cm) multinodular (≥2) hepatocellular carcinoma (HCC) and those involving macrovascular invasion (MVI). We aim to evaluate the efficacy and its variation trend and the safety of HR for these patients in three tertiary care settings. Methods: A consecutive sample of 1,824 patients with Child-Pugh A liver function and large/multinodular HCC or involving MVI and who underwent initial HR were divided into four groups: large/multinodular HCC of the previous (2000-2004, n = 496) and recent five years (2005-2010, n = 765), involving MVI of the previous (n = 242) and recent five years (n = 321). Results: Among our patient sample, the hospital mortality was less than 5% and had a downward trend. Moreover, patients in recent five years have statistically significant longer survival time. Among patients with large/multinodular HCC, patients in recent five years showed a significantly better overall survival than those in previous five years at 1-year (92% vs. 84%), 3-year (69% vs. 61%), and 5-year (45% vs. 40%) (P = 0.004). Moreover, among patients involving MVI, overall survival in recent five years was significantly higher at 1-year (83% vs. 78%), 3-year (50% vs. 41%), and 5-year (25% vs. 17%) (P= 0.033). However, the disease-free survival of recent five years was only slightly higher than that of the previous five years in the two subgroups. Conclusions: HR offers good overall survival for patients with resectable large/multinodular HCC or those involving MVI and with preserved liver function. Outcomes have tended to improve in recent decade.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15167-e15167
Author(s):  
Jay Rashmi Anam ◽  
Mihir Chandarana ◽  
Supreeta Arya ◽  
Ashwin Luis Desouza ◽  
Vikas S. Ostwal ◽  
...  

e15167 Background: Neoadjuvant chemoradiation has become the standard approach for treatment of locally advanced rectal cancers. Magnetic Resonence Imaging (MRI) is the staging modality of choice in rectal carcinoma. Recent reports have studied the impact of MRI on local recurrence and survival both in treatment naïve and post treatment settings Methods: A retrospective analysis of prospective database was performed over a period of 1 year. All pretreatment patients with carcinoma of rectum were included in the study. The status of CRM on MRI was compared to that on the histopathology and as a predictor of recurrence and survival. For analysis, the MRI scans done for patients at presentation were labeled as MRIT. This included all patients irrespective of further treatment received. Patients who were treated with NACTRT had two MRI scans. The MRI at presentation in this subset of patients was labeled as MRI1 and the reassessment MRI after NACTRT was labeled as MRI2. Thus, MRI1 represented a subset of MRIT with locally advanced tumors treated with NACTRT. All the sets of MRI scans were analyzed separately for prediction of CRM involvement and for their effect on local recurrence and survival rates. Results: 221 patients were included with a median follow-up 30 months. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRIT, MRI1 and MRI2 to predict CRM status were 50%, 62.3%, 96.5%, 5.6% and 61.8%, 50%, 55%, 95%, 6% and 54.7% and 77.8%, 63.7%, 98%, 11%, 64.5% respectively. On multivariate analysis pathological positive margins alone predicted a poor overall survival (OS) whereas involved CRM on pathology and pretreatment MRI predicted poorer disease free survival and OS Conclusions: CRM status on pathology remains the most important prognostic factor to impact overall survival, disease free survival and local recurrence. CRM status on MRI at presentation alone has significant impact on disease free survival and local recurrence. Although MRI done after neoadjuvant treatment may not predict survival, it has a role in helping modify the surgical approach with a goal to achieve a negative CRM on pathology.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 384-384
Author(s):  
Shaakir Hasan ◽  
Alexander V. Kirichenko ◽  
Paul Renz ◽  
Vijay Kudithipudi ◽  
Molly Vincent ◽  
...  

384 Background: The Albumin-Bilirubin (ALBI) model is a validated prognostic assessment of cirrhosis in hepatocellular carcinoma (HCC), stratifying patients to grades 1(ALBI-1), 2(ALBI-2), or 3(ALBI-3). We reported that ALBI distinguishes patients at higher risk for hepatic failure(HF) after stereotactic body radiotherapy (SBRT) within the Child Pugh(CP) A population. We now apply the ALBI model to both CP-A and CP-B patients after SBRT with or without orthotropic liver transplant (OLT), and assess its prognostic capability of overall survival (OS) and HF relative to the CP model. Methods: From 2009-2017, 68 patients with 81 HCC lesions and CP-A (45) or CP-B (23) cirrhosis completed SBRT in this IRB approved study. The median dose was 45 Gy (35 - 57 Gy) in 4-7 fractions. Initial ALBI and CP scores were measured against OS and progression of CP class, which was recorded every 3-4 months. Median follow-up = 18 months. Results: The median age = 62 and tumor size = 3.5 cm (1.1 Ð 11 cm). 26 patients were ALBI-1, 31 ALBI-2, and 11 ALBI-3 prior to SBRT. For all patients, 2-year local control was 96%. 1 and 2 year OS was 77% and 54%, disease free survival was 71% and 40%, and freedom from CP progression was 71% and 56%, respectively. OS was significantly different between ALBI-1, ALBI-2, and ALBI-3 patients (P = 0.01), as was progression of CP class (P<0.001). When stratified by initial CP class, there were no significant differences in survival or CP progression [Table 1]. In a subset of 37 CP-A and 15 CP-B without OLT, rates of progressive cirrhosis were better predicted by ALBI (P<0.001) than CP class (P=0.09). Conclusions: Compared to the CP model, the ALBI index more precisely predicted HF and OS in HCC patients for both early and intermediate cirrhosis. Its application may help better select candidates for OLT after SBRT, who may be at higher risk for HF than initially predicted. [Table: see text]


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Anne Marszalek ◽  
Séverine Alran ◽  
Suzy Scholl ◽  
Virginie Fourchotte ◽  
Corinne Plancher ◽  
...  

Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients.Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test.Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P<.0002), while the main prognostic factor for disease-free survival was histological tumor type (P<.0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR=2.2for suboptimal surgery), menopausal status (RR=1.47for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR=0.72).Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Feng Xiang ◽  
Linman Li ◽  
Jieling Lin ◽  
Shasha Li ◽  
Guiyuan Peng

Objective. Zao-Jiao-Ci (ZJC), a traditional Chinese medicine, is considered as a promising candidate to treat laryngeal squamous cell carcinoma (LSCC). However, the underlying molecular mechanism remains unclear. Methods. Gene expression profiles of GSE36668 were available from the GEO database, and differentially expressed genes (DEGs) of LSCC were obtained by R package; subsequently, enrichment analysis on KEGG and GO of DEGs was performed. The active ingredients of ZJC were screened from the TCMSP database, and the matched candidate targets were obtained by PharmMapper. Furthermore, we constructed protein-protein interaction (PPI) networks of DEGs and candidate targets, respectively, and we screened the core network from the merged network through combining the two PPI networks using Cytoscape 3.7.2. The key targets derived from the core network were analyzed to find out the associated KEGG signal enrichment pathway. By the GEPIA online website, Kaplan–Meier analysis was used to complete the overall survival and disease-free survival of the selected genes in the core module. Results. We identified 96 candidate targets of ZJC and 86 DEGs of LSCC, the latter including 50 upregulated genes and 36 downregulated genes. DEGs were obviously enriched in the following biological functions: extracellular structure organization, the extracellular matrix organization, and endodermal cell differentiation. The 60 key targets from the core network were enriched in the signal pathways including transcriptional misregulation cancer, cell cycle, and so on. We found that LSCC patients with high expression of HIST1H3J, HIST1H3F, and ITGA4 had worse overall survival, while higher expression of NTRK1, COPS5, HIST1H3A, and HIST1H3G had significantly worse disease-free survival. Conclusion. It suggested that the interaction between ZJC and LSCC was related to the signal pathways of transcriptional misregulation cancer and cell cycle, revealing that it may be the mechanism of ZJC in the treatment of LSCC.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Xuling Liu ◽  
Hong Gao ◽  
Jie Zhang ◽  
Dongying Xue

AbstractPrognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elahe Seyed Hosseini ◽  
Ali Nikkhah ◽  
Amir Sotudeh ◽  
Marziyeh Alizadeh Zarei ◽  
Fatemeh Izadpanah ◽  
...  

Abstract Purpose An increasing number of studies have reported a significant association between long non-coding RNAs (lncRNAs) dysregulation and pancreatic cancers. In the present study, we aimed to gather articles to evaluate the prognostic value of long non coding RNA in pancreatic cancer. Experimental design We systematically searched all eligible articles from databases of PubMed, Web of Science, and Scopus to meta-analysis of published articles and screen association of multiple lncRNAs expression with clinicopathology and/or survival of pancreatic cancer. The pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were used to analysis of overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. Results A total of 39 articles were included in the present meta-analysis. Our results showed that dysregulation of lncRNAs were linked to overall survival (39 studies, 4736 patients HR = 0.41, 95% CI 0.25 ± 0.58, random-effects in pancreatic cancer. Moreover, altered lncRNAs were also contributed to progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI (1.35–2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI 1.28–28.78). In addition, our findings revealed the association between dysregulated RNAs and clinicopathological features in this type of cancer. Conclusions In conclusion, dysregulated lncRNAs could be served as promising biomarkers for diagnosis and prognosis of pancreatic cancer.


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