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Five-CpG-based prognostic signature for predicting survival in hepatocellular carcinoma patients

Cancer Biology & Medicine 2018年第4期15卷 425-433页

作者： Feng Fang Xiaoqing Wang Tianqiang Song Department of Hepatobiliary Cancer Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer

Objective:Hepatocellular carcinoma(HCC)is a common malignancy associated with high morbidity and mortality rates worldwide.Early diagnosis plays an important role in the improvement of HCC prognosis.Methods:In this study,we conducted a comprehensive analysis of HCC DNA methylation and gene expression datasets in The Cancer Genome Atlas(TCGA),to identify a prognostic signature for HCC diagnosis and survival prediction.First,we identified differential methylation CpG(dmCpG)sites in HCC samples and compared them with those in adjacent normal liver tissues;this was followed by univariate analysis and Sure Independence Screening(SIS)in the training set.The robustness of the identified prognostic signature was evaluated using the testing set.To explore the biological processes involved in HCC progression,we also performed functional enrichment analysis for overlapping genes between genes containing dmCpG sites(DMGs)and differential expression genes(DEGs)in HCC patients,using data from the Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results:As a result,we identified five CpG sites that were significantly associated with HCC survival through univariate analysis and SIS.Univariate analysis of clinical characteristics identified age and risk factors(including alcohol consumption and smoking)as independent factors that indicated HCC survival.Multivariate analysis indicated that the integrated prognostic signature(weighted combination of the five CpG sites)that took age and risk factors into consideration resulted in more accurate survival prediction.Conclusions:This study provides a novel signature for predicting HCC survival,and should be helpful for early HCC diagnosis and personalized treatment.

关键词： Hepatocellular carcinoma methylation prognosis prognostic signature TCGA

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Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 983-997页

作者： Zi-Lin Huang Wang Li Qi-Feng Chen Pei-Hong Wu Lu-Jun Shen Department of Medical Imaging and Interventional Radiology Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangzhou 510060Guangdong ProvinceChina

BACKGROUND Hepatitis B virus,together with hepatitis C virus,has been recognized as the leading causes of hepatocellular carcinoma(HCC).Long non-coding RNAs(lncRNAs)have been suggested in increasing studies to be the potential prognostic factors for HCC.However,the role of combined application of lncRNAs in estimating overall survival(OS)for hepatitis virus positive HCC(VHCC)is uncertain.AIM To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.METHODS The expression patterns of lncRNAs,as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database.The R package was adopted to obtain the differentially expressed lncRNAs(DElncRNAs).LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis,so as to construct a least absolute shrinkage and selection operator(LASSO)model.Subsequently,the constructed lncRNA signature was developed and validated.Afterwards,the prognostic nomogram was established,which combined the as-established lncRNA signature as well as the clinical features.Meanwhile,subgroup analysis stratified by the virus type was also performed.Finally,the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly coexpressed genes.RESULTS A total of 1420 DElncRNAs were identified,among which 406 were significant in univariate Cox regression analysis.LASSO regression confirmed 8 out of the 406 lncRNAs,including AC005722.2,AC107959.3,AL353803.1,AL589182.1,AP000844.2,AP002478.1,FLJ36000,and NPSR1-AS1.Then,the prognostic risk score was calculated.Our results displayed a significant association between the risk model and the OS of VHCC[hazard ratio=1.94,95%confidence interval(CI):1.61-2.34,log-rank P=2e-10].The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC.Furthermore,a nomogram was plotted,and the concordance index of internal validation was 0.763(95%CI:0.700-0.826).Moreov

关键词： Long non-coding RNAs Hepatitis virus Hepatocellular carcinoma prognostic signature Least absolute shrinkage and selection operator

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A new tumor-associated antigen prognostic scoring system for spontaneous ruptured hepatocellular carcinoma after partial hepatectomy

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Cancer Biology & Medicine 2018年第4期15卷 415-424页

作者： Jingjing Wu Peng Zhu Zhanguo Zhang Bixiang Zhang Chang Shu Lin Chen Renjie Feng Abdoul aziz Mba'nbo koumpa Ganxun Li Qianyun Ge Department of Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China Department of Neurology Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhan 430030China

Objective:Spontaneous hepatocellular carcinoma(HCC)rupture can be fatal,and hepatic resection could achieve a favorable long-term survival among all strategies of tumor rupture.However,there is no available prognostic scoring system for patients with ruptured HCC who underwent partial hepatectomy.Methods:From January 2005 to May 2015,129 patients with spontaneous HCC rupture underwent partial hepatectomy.Preoperative clinical data were collected and analyzed.Independent risk factors affecting overall survival(OS)were used to develop the new scoring system.Harrell’s C statistics,Akaike information criterion(AIC),the relative likelihood,and the log likelihood ratio were calculated to measure the homogeneity and discriminatory ability of a prognostic system.Results:In the multivariable Cox regression analysis,three factors,including tumor size,preoperativeα-fetoprotein level,and alkaline phosphatase level,were chosen for the new tumor-associated antigen(TAA)prognostic scoring system.The 1-year OS rates were 88.1%,43.2%,and 30.2%for TAA scores of 0–5 points(low-risk group),6–9 points(moderate-risk group),and 10–13points(high-risk group),respectively.The TAA scoring system had superior homogeneity and discriminatory ability(Harrell’s C statistics,0.693 vs.0.627 and 0.634;AIC,794.79 vs.817.23 and 820.16;relative likelihood,bothprognostic scoring system is simple and effective in predicting both OS and DFS of patients with spontaneous ruptured HCC.

关键词： Spontaneous rupture prognostic scoring system homogeneity discriminatory ability overall survival disease-free survival hepatocellular carcinoma

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A Novel prognostic Approach to Predict Recovery in Patients with Chronic Disorders of Consciousness

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Neuroscience Bulletin 2019年第5期35卷 953-954页

作者： Wangxiao Bao Xiaoxia Li Benyan Luo Department of Neurology First Affiliated Hospital Collaborative Innovation Center for Brain Science Zhejiang University School of Medicine

Severe brain injury can lead to acute or chronic disorders of consciousness (DOC), and the latter represents a more critical challenge in diagnosis and management. For most chronic unconsciousness survivors with preserved sleepwake cycles, including vegetative state (VS) and minimally conscious state (MCS), levels of consciousness are commonly monitored and determined based on behavioral evidence. VS, also termed unresponsive wakefulness syndrome (UWS), is characterized by complete absence of awareness and may be associated with poor recovery, while MCS exhibit discernible behavioral signs of environmental or self- awareness [1]. Since nearly 40% patients in MCS are initially misdiagnosed as VS/UWS due to the limitation of the existing diagnostic criterion, it is therefore necessary to define the accurate diagnostic and prognostic categorization for long-term outcome [2].

关键词： Chronic Disorders of Consciousness prognostic

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Correlation of serum albumin and prognostic nutritional index with outcomes following pancreaticoduodenectomy

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World Journal of Clinical Cases 2019年第1期7卷 28-38页

作者： Narongsak Rungsakulkij Pongsatorn Tangtawee Wikran Suragul Paramin Muangkaew Somkit Mingphruedhi Suraida Aeesoa Department of Surgery Faculty of Medicine Ramathibodi Hospital Mahidol University

BACKGROUND Pancreaticoduodenectomy(PD) is a complex surgical procedure with a high morbidity rate. The serious complications are major risk factors for poor longterm surgical outcome. Studies have reported an association between early postoperative prognostic nutritional index(PNI) and prediction of severe complications after abdominal surgery. However, there have been no studies on the use of early postoperative PNI for predicting serious complications following PD.AIM To analyze the risk factors and early postoperative PNI for predicting severe complications following PD.METHODS We retrospectively analyzed 238 patients who underwent PD at our hospital between January 2007 and December 2017. The postoperative complications were classified according to the Dindo-Clavien classification. Grade Ⅲ-Ⅴ postoperative complications were classified as serious. The risk factors for serious complications were analyzed by univariate analysis and multivariate logistic regression analysis.RESULTS Overall complications were detected in 157 of 238 patients(65.9%) who underwent PD. The grade Ⅲ-Ⅴ complication rate was 26.47%(63/238 patients).The mortality rate was 3.7%(9/238 patients). Multivariate logistic regression analysis revealed that preoperative serum albumin [odds ratio(OR): 0.883, 95%confidence interval(CI): 0.80-0.96; P < 0.01] and PNI on postoperative day 3 <40.5(OR: 2.77, 95%CI: 1.21-6.38, P < 0.05) were independent factors associated with grade Ⅲ-Ⅴ postoperative complications.CONCLUSION Perioperative albumin is an important factor associated with serious complications following PD. Low early postoperative PNI(< 40.5) is a predictor for serious complications.

关键词： Postoperative complications Pancreatectomy Serum albumin Risk factors prognostic nutritional index

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C-reactive protein may be a prognostic factor for the whole gastroenteropancreatic neuroendocrine tumor group

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World Journal of Gastrointestinal Oncology 2019年第2期11卷 139-152页

作者： ?mer Koma? G?ksel Bengi ?zgül Sa?ol Mesut Akarsu Department of Internal Medicine Dokuz Eylul University Faculty of Medicine Department of Gastroenterology Dokuz Eylul University Faculty of Medicine Department of Pathology Dokuz Eylul University Faculty of Medicine

BACKGROUND Long non-coding RNAs(lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer(GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary.AIM To identify independent prognostic markers for the whole gastroenteropancreatic neuroendocrine tumor(GEP-NET) group.METHODS Ninety-three patients diagnosed with GEP-NETs within a specified period were included in this study. Patient data were retrospectively analyzed. The relationships between all independent variables and 5-year survival status calculated during the follow-up period(months) were assessed. In addition, the relationships between the independent variables were investigated.RESULTS When 5-year survival rate was compared, a statistically significant relationship between the age at diagnosis, male gender, tumor size, tumor stage, liver and/or distant metastasis, and tumor grade determined by the Ki-67 level and mitotic count, and the level of C-reactive protein(CRP), was observed. The meansurvival(overall survival) of the study group was 102.5 ± 6.3(SD) mo. The percentages of 1, 3 and 5-year survival were 90%, 72%, and 61%, respectively. In63 of 93 patients, Ki-67 and the mitotic count determined the same grade. The Ki-67 levels in 29 patients and the mitotic count in only 1 patient were in the higher grade. The risk of death increased by 4% for every 1 year increase at the diagnosis age and was 2.0-fold higher for male patients, 3.0-fold higher for G3 according to the mitotic count, 3.7-fold higher for G3 according to the Ki-67 level, 12.7-fold higher for cases with tumor stage 3 or 4 by a 1 cm increase in the ratio of 9% in tumor size, and 6.1-fold higher for patients with liver metastasis for every 1 mg/dL increase in the ratio of 1.5% in CRP level. There was a significant difference betw

关键词： Gastroenteropancreatic neuroendocrine tumors C-reactive protein prognostic factor Neuroendocrine tumors Gastrointestinal system

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Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

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World Journal of Gastroenterology 2019年第34期25卷 5026-5048页

作者： Orsolya Galamb Barbara K Barták Alexandra Kalmár Zsófia B Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz Béla Molnár Molecular Medicine Research Group Hungarian Academy of SciencesBudapest H-1088Hungary 2nd Department of Internal Medicine Semmelweis UniversityBudapest H-1088Hungary

Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.

关键词： Long non-coding RNA Colorectal cancer Colorectal adenoma Circulating long non-coding RNAs Exosome Biomarker Diagnostic marker prognostic marker

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Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

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Chinese Journal of Cancer Research 2019年第5期31卷 771-784页

作者： Han-Chen Huang Xian-Zi Wen Hua Xue Run-Sheng Chen Jia-Fu Ji Lei Xu Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Guangdong Geneway Decoding Bio-Tech Co.Ltd Foshan 528316China Centre for Cognitive Machines and Computational Health(CMaCH) School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Computer Science and Engineering The Chinese University of Hong KongHong Kong 999077China

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

关键词： Gastric cancer gene expression profile prognostic biomarker phosphoglucose isomerase tumor metabolism

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prognostic value of plasma C-reactive protein in the evaluation of paraquat poisoning patients

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Asian Pacific Journal of Tropical Biomedicine 2015年第10期5卷 841-844页

作者： Zong Ning Yu-Long Bai Hua Lu Kang-Lin Mo Department of Emergency The First Affiliated Hospital of Guangxi Medical University

Objective: To investigate the prognostic value of plasma C-reactive protein(CRP) level in patients with paraquat poisoning.Methods: This study included 162 patients with paraquat poisoning. The data of plasma paraquat, CRP level and arterial blood gas were analyzed. Cox regression analysis was applied to evaluate the risk factors of prognosis. Receiver operating characteristics curve analysis and area under curve were used to calculate the predictive power of significant variable. Differences in patient survival were determined using the Kaplan–Meier method and a log-rank test.Results: Plasma CRP level was significantly increased in non-survival patients compared with survival patients(P prognostic marker of mortality within 30 days. The receiver operating characteristics curve analysis indicated that area under curve of plasma CRP level was0.867(95% CI: 0.81–0.93), and the cut-off value was 18 mg/L, and patients with CRP level over this value had a poor survival time compared with those with less than this value.Conclusions: These results suggest that plasma CRP level is distinct increased in patients with paraquat poisoning, and the plasma CRP level may be useful for the prediction of prognosis in paraquat poisoning.

关键词： paraquat poisoning prognosis prognostic mortality

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prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: A meta-analysis

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World Journal of Gastrointestinal Oncology 2020年第12期12卷 1443-1455页

作者： Ling Tan Zi-Lin Liu Zhou Ma Zhou He Lin-Han Tang Yi-Lei Liu Jiang-Wei Xiao Department of Gastrointestinal Surgery Clinical Medical College and The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODS We performed a systematic review and searched Pub Med,Embase(Ovid),MEDLINE(Ovid),Web of Science,and Cochrane Library from January 1,2000 until January 1,2020.Two reviewers examined all the publications independently and extracted the relevant data.Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment(LNs≥12 vs LNs<12).The primary endpoints were the overall survival(OS)and disease-free survival(DFS).RESULTS Nine articles were included in the meta-analyses.Statistical analysis revealed a statistically significant difference in OS[hazard ratio(HR)=0.76,95%confidence interval(CI):0.66-0.88,I2=12.2%,P=0.336],DFS(HR=0.76,95%CI:0.63-0.92,I2=68.4%,P=0.013),and distant recurrence(DR)(HR=0.63,95%CI:0.48-0.93,I2=30.5%,P=0.237)between the LNs≥12 and LNs<12 groups,but local recurrence(HR=0.67,95%CI:0.38-1.16,I2=0%,P=0.348)showed no statistical difference.Moreover,subgroup analysis of LN negative patients revealed a statistically significant difference in DFS(HR=0.67,95%CI:0.52-0.88,I2=0%,P=0.565)between the LNs≥12 and LNs<12 groups.CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer,our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’OS,DFS,and DR.

关键词： Rectal cancer Neoadjuvant therapy Lymph node prognostic Overall survival Meta-analysis

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