scholarly journals Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6375 ◽  
Author(s):  
Xiuzhi Zhang ◽  
Chunyan Kang ◽  
Ningning Li ◽  
Xiaoli Liu ◽  
Jinzhong Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Disease Free Survival ◽  
Free Survival ◽  
Oncomine Database ◽  
Key Genes ◽  
Disease Free

Background Alcohol-related hepatocellular carcinoma (HCC) was reported to be diagnosed at a later stage, but the mechanism was unknown. This study aimed to identify special key genes (SKGs) during alcohol-related HCC development and progression. Methods The mRNA data of 369 HCC patients and the clinical information were downloaded from the Cancer Genome Atlas project (TCGA). The 310 patients with certain HCC-related risk factors were included for analysis and divided into seven groups according to the risk factors. Survival analyses were applied for the HCC patients of different groups. The patients with hepatitis B virus or hepatitis C virus infection only were combined into the HCC-V group for further analysis. The differentially expressed genes (DEGs) between the HCCs with alcohol consumption only (HCC-A) and HCC-V tumors were identified through limma package in R with cutoff criteria│log2 fold change (logFC)|>1.0 and p < 0.05. The DEGs between eight alcohol-related HCCs and their paired normal livers of GSE59259 from the Gene Expression Omnibus (GEO) were identified through GEO2R (a built-in tool in GEO database) with cutoff criteria |logFC|> 2.0 and adj.p < 0.05. The intersection of the two sets of DEGs was considered SKGs which were then investigated for their specificity through comparisons between HCC-A and other four HCC groups. The SKGs were analyzed for their correlations with HCC-A stage and grade and their prognostic power for HCC-A patients. The expressional differences of the SKGs in the HCCs in whole were also investigated through Gene Expression Profiling Interactive Analysis (GEPIA). The SKGs in HCC were validated through Oncomine database analysis. Results Pathological stage is an independent prognostic factor for HCC patients. HCC-A patients were diagnosed later than HCC patients with other risk factors. Ten SKGs were identified and nine of them were confirmed for their differences in paired samples of HCC-A patients. Three (SLC22A10, CD5L, and UROC1) and four (SLC22A10, UROC1, CSAG3, and CSMD1) confirmed genes were correlated with HCC-A stage and grade, respectively. SPP2 had a lower trend in HCC-A tumors and was negatively correlated with HCC-A stage and grade. The SKGs each was differentially expressed between HCC-A and at least one of other HCC groups. CD5L was identified to be favorable prognostic factor for overall survival while CSMD1 unfavorable prognostic factor for disease-free survival for HCC-A patients and HCC patients in whole. Through Oncomine database, the dysregulations of the SKGs in HCC and their clinical significance were confirmed. Conclusion The poor prognosis of HCC-A patients might be due to their later diagnosis. The SKGs, especially the four stage-correlated genes (CD5L, SLC22A10, UROC1, and SPP2) might play important roles in HCC development, especially alcohol-related HCC development and progression. CD5L might be useful for overall survival and CSMD1 for disease-free survival predication in HCC, especially alcohol-related HCC.

scholarly journals Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Chongyang Ma ◽  
Tian Xu ◽  
Xiaoguang Sun ◽  
Shuang Zhang ◽  
Shuling Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Ppi Network ◽  
Free Survival ◽  
Disease Free

Liver cancer is the fourth leading cause of cancer death worldwide, and hepatocellular carcinoma (HCC) accounts for the greatest proportion of these deaths. Baicalein, a flavonoid isolated from the root of Scutellariae radix, is considered a potential candidate to treat HCC. However, the underlying molecular mechanisms remain poorly understood. In the present study, a network pharmacological approach was combined with microarray data (GSE95504) acquired from the Gene Expression Omnibus database to reveal the therapeutic mechanisms of action of baicalein at a systemic level. We identified 38 baicalein targets and 76 differently expressed genes (DEGs) following treatment with baicalein, including 55 upregulated and 21 downregulated genes. The DEGs were significantly enriched in the biological functions of apoptosis, endoplasmic reticulum stress, and PERK-mediated unfolded protein response. Protein-protein interaction (PPI) network construction and topological screening revealed a core module of PPIs including two baicalein targets, TP53 and CDK1, and two downregulated DEGs, HSPA1A and HSPA1B. Expression and survival data for these genes in the module derived from Gene Expression Profiling Interactive Analysis (GEPIA) were subjected to Kaplan–Meier analysis of overall survival and disease-free survival. Overexpression of CDK1, BRCA1, TUBB, HSPA1A, HSPA1B, and HSPA4 was associated with significantly worse overall survival, while overexpression of CDK1, CLU7, BRCA1, and TUBB was associated with significantly worse disease-free survival. These data suggest that baicalein exerts therapeutic effects against HCC via a PPI network involving TP53, CDK1, HSPA1A, and HSPA1B.

scholarly journals HULC and H19 Played Different Roles in Overall and Disease-Free Survival from Hepatocellular Carcinoma after Curative Hepatectomy: A Preliminary Analysis from Gene Expression Omnibus

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zongguo Yang ◽  
Yunfei Lu ◽  
Qingnian Xu ◽  
Bozong Tang ◽  
Cheol-Keun Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Vascular Invasion ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Tumor Tissues ◽  
Disease Free

Objective. This study aimed to evaluate the relationships between long noncoding RNAs (lncRNAs) in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and survival.Methods. We correlated the lncRNAs in tumor tissues with HCC survival and clinicopathological features based on Gene Expression Omnibus expression profile GSE36376.Results. Eight lncRNAs and 240 HCC patients were included. Cox regression analysis indicated that HULC was a positive factor for HCC overall survival (HR = 0.885, 95% CI = 0.797–0.983, andP=0.023) and disease-free survival time (HR = 0.913, 95% CI = 0.835–0.998, andP=0.045). H19 and UCA1 were both demonstrated to be risk factors of HCC disease-free survival in multivariate Cox model (HR = 1.071, 95% CI = 1.01–1.137, andP=0.022and HR = 2.4, 95% CI = 1.092–5.273, andP=0.029, resp.). But Kaplan-Meier method showed no significant association between UCA1 and HCC disease-free survival (log rankP=0.616). Logistic regression demonstrated that H19 was overexpressed in HBV-infected patients (OR = 1.14, 95% CI = 1.008–1.29, andP=0.037). HULC had a significant association with vascular invasion (OR = 0.648, 95% CI = 0.523–0.803, andP<0.001). H19 and MEG3 were both considered to be risk factors for high AFP level (OR = 1.45, 95% CI = 1.277–1.646, andP<0.001and OR = 1.613, 95% CI = 1.1–2.365, andP=0.014, resp.).Conclusions. Contributing to decreased susceptibility to vascular invasion, upregulation of HULC in tumor tissues was positively associated with HCC survival. In contrast, H19 overexpression might be risk factor for HCC aggressiveness and poor outcomes.

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

Staged management of cardiac disease and concomitant early lung cancer: a 20-year single-center experience

2020 ◽  
Author(s):  
Jérémy Tricard ◽  
Daniel Milad ◽  
Anaëlle Chermat ◽  
Serge Simard ◽  
Yves Lacasse ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Free Survival ◽  
Cardiac Procedure ◽  
Independent Risk Factors ◽  
Group 2 ◽  
Disease Free ◽  
Group 1

Abstract OBJECTIVES The association of unstable heart disease and resectable lung cancer is rare. The impacts of staged management, cardiac surgery with cardiopulmonary bypass (CPB) versus angioplasty, on long-term survival and cancer recurrence remain debated. We report our experience using staged management. METHODS From 1997 to 2016, 107 patients were treated at the Quebec Heart and Lung Institute: 72 underwent cardiac surgery with CPB (group 1), 35 were treated with angioplasty (group 2), followed by oncological pulmonary resection. RESULTS Two postoperative deaths (3%) and 1 ischaemic heart complication (1%) were reported in group 1. One death (3%) was reported in group 2. Two-year overall survival was 82% (59/72) in group 1 and 80% (28/35) in group 2; 5-year overall survival was 62% (33/53) in group 1 and 63% (19/30) in group 2. Two-year disease-free survival in group 1 was 79% (57/72) and 77% (27/35) in group 2; 5-year disease-free survival was 58% (31/53) in group 1 and 60% (18/30) in group 2. The independent risk factors for death after thoracic surgery were transfusions (P = 0.004) and grade ≥3 complications (P = 0.034). Independent risk factors for recurrence included the cancer stage (P &lt; 0.001) and, paradoxically, a shorter delay between cardiac and lung procedures (P = 0.031). CONCLUSIONS When a staged management remains feasible after cardiac procedure, oncological outcomes of patients with cardiopathy and lung cancer are satisfactory. CPB does not seem to be deleterious. The delay between procedures should intuitively be as small as possible but not at the expense of good recovery after the cardiac procedure.

A 10-year retrospective analysis of risk factors, patterns of cancer recurrence, and survival after liver transplant for cirrhosis and hepatocellular carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4617-4617
Author(s):  
A. O. Kaseb ◽  
M. Bansal ◽  
I. Wollner ◽  
V. Shah ◽  
D. Moonka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Transplant ◽  
Disease Free Survival ◽  
Small Sample ◽  
Prognostic Indicators ◽  
Term Survival ◽  
Free Survival ◽  
Pathologic Features ◽  
Disease Free

4617 Introduction: Determining eligible patients who are likely to have better outcomes following orthotopic liver transplant (OLT) for cirrhosis and hepatocellular carcinoma (HCC) is an ongoing challenge. In addition, tumor recurrence represents a major limitation of long-term survival in this setting. Patients and Methods: The study analyzed 72 OLT recipients for cirrhosis and HCC, between 1996–2006. The endpoints were frequency, patterns, localization, and risk factors of recurrence. Survival from time of OLT to recurrence was compared with primary tumor and patient characteristics, and type of treatment received pre- and post-OLT using univariate and multivariate analyses. Survival was estimated using Kaplan-Meier plots. Results: 13 recurrences (18%) occurred after a median of 33.4 months follow up (6–123 months). 11/13 (84.6%) were distant metastases. Using cox regression analysis and log-rank p-value; bilobar involvement, a tumor number of =3, tumor grade 2 or 3, size >3 cm, vascular invasion, and elevated AFP at diagnosis were all positively associated with recurrence (either distant or any). Tumors that met Milan criteria were associated with a lower likelihood of recurrence. In addition, Pre and post-OLT treatments were not found to be associated with significantly improved disease-free survival. Conclusions: Our analyses confirmed that advanced pathologic features are independently associated with significantly shorter disease-free survival. Pre- and post-OLT treatment modalities were not observed to improve disease-free survival for patients with bad prognostic indicators. However, this is limited due to our small sample size and our univariate anaylsis. We conclude that careful patient selection based on prognostic indicators would maximize benefit from use of this expensive and limited resource. [Table: see text] No significant financial relationships to disclose.

Efficacy trend of hepatic resection for hepatocellular carcinoma with large multinodular tumor or macrovascular invasion.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Jian-Hong Zhong ◽  
Le-Qun Li ◽  
Xin-Ping Ye ◽  
Yang Ke ◽  
Lin Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Hepatic Resection ◽  
Tertiary Care ◽  
Disease Free Survival ◽  
Recent Decade ◽  
Free Survival ◽  
Disease Free

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.

Prognosis of hepatic failure with the albumin-bilirubin model for hepatocellular carcinoma after stereotactic body radiotherapy with and without transplant.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 384-384
Author(s):  
Shaakir Hasan ◽  
Alexander V. Kirichenko ◽  
Paul Renz ◽  
Vijay Kudithipudi ◽  
Molly Vincent ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatic Failure ◽  
Stereotactic Body Radiotherapy ◽  
Disease Free Survival ◽  
Median Dose ◽  
Free Survival ◽  
Prognostic Assessment ◽  
Disease Free

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]

scholarly journals Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Anne Marszalek ◽  
Séverine Alran ◽  
Suzy Scholl ◽  
Virginie Fourchotte ◽  
Corinne Plancher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Surgical Procedure ◽  
Menopausal Status ◽  
Disease Free Survival ◽  
Tumor Type ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

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.

scholarly journals Pre-treatment Haemoglobin Concentration is a Prognostic Factor in Patients with Early-stage Breast Cancer

2005 ◽  
Vol 33 (3) ◽  
pp. 319-328 ◽  
Author(s):  
EG Kandemir ◽  
A Mayadagli ◽  
O Turken ◽  
M Yaylaci ◽  
A Ozturk
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Early Stage ◽  
Haemoglobin Concentration ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

We investigated the prevalence of anaemia (haemoglobin concentration < 12 g/dl) in 336 women with early-stage breast cancer and its association with other known prognostic factors. The median follow-up period was 60.5 months (range 9-123 months). Seventy-nine women (23.5%) had a low pre-treatment haemoglobin concentration, but anaemia was not correlated with age, tumour size, nodal status, histological grade or hormone receptor status. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with anaemia at the time of diagnosis than in patients with normal haemoglobin concentrations. Anaemia remained a significant prognostic factor for disease-free survival and overall survival in the multivariate analysis (relative risk, 1.884 and 1.785, respectively). These results suggest that pre-treatment haemoglobin concentration is an independent prognostic factor in patients with early-stage breast cancer.

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