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Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

World Journal of Gastroenterology 2019年第2期25卷 220-232页

作者： Jing-Xian Gu Xing Zhang Run-Chen Miao Xiao-Hong Xiang Yu-Nong Fu Jing-Yao Zhang Chang Liu Kai Qu Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong University

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogr

关键词： Long non-coding RNAs Hepatocellular carcinoma Prognostic signature recurrence-free survival Least absolute shrinkage and selection operator

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Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

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World Journal of Gastrointestinal Oncology 2012年第10期4卷 207-215页

作者： Sabrina C Wentz Zhi-Guo Zhao Yu Shyr Chan-Juan Shi Kay Washington Nipun B Merchant Fen Xia A Bapsi Chakravarthy Department of Pathology The Johns Hopkins HospitalBaltimoreMD 21201United States Department of Biostatistics Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Pathology Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Surgery Vanderbilt University Medical CenterNashvilleTN 37215United States Department of Radiation Oncology Vanderbilt University Medical CenterNashvilleTN 37215United States

AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.

关键词： Pancreatic adenocarcinoma Lymph node ratio Carbohydrate antigen 19-9 recurrence-free survival Overall survival

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Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2018年第45期24卷 5154-5166页

作者： Li-Yan Xue Xiu-Min Qin Yong Liu Jun Liang Hua Lin Xue-Min Xue Shuang-Mei Zou Mo-Yan Zhang Bai-Hua Zhang Zhou-Guang Hui Zi-Tong Zhao Li-Qun Ren Yue-Ming Zhang Xiu-Yun Liu Yan-Ling Yuan Jian-Ming Ying Shu-Geng Gao Yong-Mei Song Gui-Qi Wang Sanford M Dawsey Ning Lu Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Center for Cancer Precision Medicine Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Endoscopy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Medical Record National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College The 2nd Department of Thoracic Surgery Hunan Cancer Hospital The Affiliated Cancer Hospital of Xiangya School of Medicine CSU State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Pathology Chengde Medical College Metabolic Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute

AIM To identify the clinicopathological characteristics of pT1 N0 esophageal squamous cell carcinoma(ESCC) that are associated with tumor recurrence. METHODS We reviewed 216 pT1 N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrencefree survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence(≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models.RESULTS Forty-seven(24%) patients had a recurrence at 3 to 178(median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence(Hazard ratios = 3.26, 3.42, and 2.06, P recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were ind

关键词： Esophageal squamous cell carcinoma Tumor recurrence Lymph node negative esophageal cancer recurrence-free survival Clinicopathological parameters

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Long-Term Outcomes and Prognosis of Transrectal High-Intensity Focused Ultrasound Therapy for Patients with Localized Prostate Cancer—Therapy after recurrence and Predictive Factors

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Open Journal of Urology 2017年第6期7卷 87-102页

作者： Mutsuo Hayashi Tetsutaro Hayashi Kiyotaka Oka Keisuke Goto Shunsuke Shinmei Yoji Inoue Katsumi Inoue Department of Urology Takanobashi Central Hospital Hiroshima Japan Department of Urology Hiroshima University Hospital Hiroshima Japan Department of Urology Mazda Hospital Hiroshima Japan

Objectives: To evaluate the outcomes and prognosis of high-intensity focused ultrasound (HIFU) therapy for patients with localized prostate cancer, and identify suitable candidates for this therapy by investigating the predictive factors. Methods: The 224 patients (low 54, intermediate 111 and high-risk patients 59) with T1-2 stage were treated using the Sonablate device and followed for over 12 months after treatment. recurrence was determined based on histological findings, prostate-specific antigen (PSA) failure and local or distant metastasis. The factors which are predicting variables with potential effects were investigated by Kaplan-Meier and multivariate analysis. Results: A total of 255 treatment sessions (193 with one, 31 with two) were performed. No patients died of prostate cancer, but 15 died of other causes and 14 patients were lost during follow-up. The 7-year recurrence-free survival (RFS) rates in all patients were 75%, and 5-year RFS rates were 98%, 84% and 59% in the low, intermediate and high-risk patients respectively. In the 216 patients who underwent histological examination at 6 months or later after HIFU, 25 (12%) were positive. In 77 patients with recurrence after first-HIFU, the second treatments were hormonal therapy and HIFU. Of the 31 patients who underwent a second HIFU, the 5-year RFS rates were 64%, and 5-year RFS rates were 100%, 74% and 33% in the low, intermediate and high-risk patients. The significant predictor for recurrence was risk-group, T-stage (T1 vs T2), Gleason score (≤3 + 4 and ≥4 + 3), pretreatment PSA (Conclusions: Prognosis of HIFU for Patients with localized prostate cancer was good, and the low and intermediate-risk patients with T1-staging are suitable indications for HIFU. Effective predictors for outcomes were risk-group, T-stage, Gleason score, pretreatment PSA and nadir PSA.

关键词： High-Intensity Focused Ultrasound Localized Prostate Cancer Treatment Outcomes and Prognosis recurrence-free Survival Treatment Predictor

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Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

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World Journal of Gastroenterology 2013年第34期19卷 5622-5632页

作者： Daniele Nicolini Gianluca Svegliati-Baroni Roberto Candelari Cinzia Mincarelli Alessandra Mandolesi Italo Bearzi Federico Mocchegiani Andrea Vecchi Roberto Montalti Antonio Benedetti Andrea Risaliti Marco Vivarelli Division of Hepatobiliary and Transplant Surgery Department of Gastroenterology and TransplantationPolytechnic University of Marche Division of Gastroenterology Department of Gastroenterology and TransplantationPolytechnic University of Marche Division of Interventional Radiology Department of Radiological SciencesPolytechnic University of Marche Division of Pathology Department of PathologyPolytechnic University of Marche Division of Hepatobiliary and Transplant Surgery Department of Medical and Biological SciencesUniversityof Udine

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(Precurrence-free survival was higher in DEB-TACE-treated patients than in convent

关键词： Liver transplantation Hepatocellular carcinoma Transcatheter arterial chemoembolization Doxorubicin-eluting bead Tumor histology recurrence-free survival Locoregional therapies

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Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: Strategies using degradable starch microspheres transcatheter arterial chemo-embolization

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World Journal of Hepatology 2015年第12期7卷 1694-1700页

作者： Antonio Orlacchio Fabrizio Chegai Stefano Merolla Simona Francioso Costantino Del Giudice Mario Angelico Giuseppe Tisone Giovanni Simonetti Department of Diagnostic and Molecular Imaging Radiation Therapy and Interventional Radiology University Hospital Tor Vergata Liver Unit University Hospital Tor Vergata Organ Transplantation Unit University Hospital Tor Vergata

AIM: To evaluate the downstaging rates in hepatitis C virus-patients with hepatocellular carcinoma(HCC), treated with degradable starch microspheres transcatheter arterial chemoembolization(DSM-TACE), to reach new-Milan-criteria(nM C) for transplantation. METHODS: This study was approved by the Ethics Committee of our institution. From September 2013 to March 2014 eight patients(5 men and 3 women) with liver cirrhosis and multinodular HCC, that did not meet n MC at baseline, were enrolled in this study. Patients who received any other type of treatment such as termal ablation or percutaneous ethanol injection were excluded. DSM-TACE was performed in all patients using Embo Cept? S and doxorubicin. Baseline and follow-up computed tomography or magnetic resonance imaging was assessed measuring the longest enhancing axial dimension of each tumor according to the modified Response Evaluation Criteria In Solid Tumors measure-ments, and medical records were reviewed.RESULTS: DSM-TACE was successfully performed in all patients without major complication. We treated 35 lesions(mean 4.3 per patient). Six of eight patients(75%) had their HCC downstaged to meet nM C. Every patient whose disease was downstaged eventually underwent transplantation. The six patients who received transplant were still living at the time of this writing, without recurrence of HCC. Baseline age(P = 0.25), Model for End-stage Liver Disease score(P = 0. 77), and α-fetoprotein level(P = 1.00) were similar between patients with and without downstaged HCC. CONCLUSION: DSM-TACE represents a safely and effective treatment option with similar safety and efficacy of conventional chemoembolization and could be successfully performed also for downstaging disease in patients without n MC, allowing them to reach liver transplantation.

关键词： Hepatocellular carcinoma Transcatheterarterial chemoembolization Liver transplantation Degradable starch microspheres New-Milan-criteria recurrence-free survival Locoregional therapies

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