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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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Adjuvant therapy for intrahepatic carcinoma after surgical resection:chemotherapy and future perspectives

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Hepatobiliary Surgery and Nutrition 2021年第6期10卷 878-880页

作者： Wei Zhang Tianqiang Song Department of Hepatobiliary Cancer Research Center for Prevention and Treatment of Liver CancerTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjinChina

Intrahepatic cholangiocarcinoma is a highly aggressive and malignant liver cancer.The main reason for its poor prognosis is the low opportunity of surgery and the high rates of postoperative recurrence and metastasis.Thus,reducing postoperative recurrence and metastasis rate is the key to improving prognosis.Although some retrospective studies have attested to the value of adjuvant therapy in patients with R1 resection or N1/T3/T4 intrahepatic cholangiocarcinoma(1),no recommended standard yet exists in intrahepatic cholangiocarcinoma primarily because the only 2 completed phase III clinical trials,the PRODIGE 12-ACCORD 18 trial(2)and the BILCAP trial(3),failed to achieve survival benefit in the chemotherapy arm in the adjuvant setting.However,one of the possible reasons for the negative results of the 2 studies is that patients with R1/N1/T3/T4 were not differentiated.One randomized phase III trials(JCOG1202,ASCOT)of adjuvant S-1 therapy vs.observation alone in resected biliary tract cancer(4)and one trial(ACTICCA-1 trial)of adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma(5)are ongoing and awaiting future results.

关键词： resection chemotherapy intrahepatic

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The Relationship of Elevated Preoperative Serum CA19-9 Levels and the Early Recurrence of Single Small Hepatocellular Carcinoma

The Relationship of Elevated Preoperative Serum CA19-9 Level...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者： Shaohua Ren Tianqiang Song Tianjin Medical University Cancer Institute and Hospital

Background : Determining the risk factors for the recurrence of single small HCC（≤ 3 cm） may contribute to the implementation of additional treatment strategies in clinical practice.Methods: A total of 276 patients with single small primary HCC（≤ 3 cm） who received initial treatment from September 2010 to September 2019 were retrospectively enrolled in the primary cohort through random resolution to establish a nomogram. The remaining 137 patients were used to verify the accuracy of the nomogram.Results: The median RFS for the primary and the validation cohorts were 43.0 and 51.0 months,respectively. The multivariate analysis showed that age, hepatitis, preoperative CA19-9 level, and Child-Pugh score were independent risk factors for recurrence-free survival. On the basis of these four variables, the nomogram was developed. Patients with normal preoperative CA19-9 levels had better RFS than those with abnormal preoperative CA19-9 levels. Especially, among the AFP-negative patients, those with normal preoperative CA19-9 levels had better RFS than those with abnormal preoperative CA19-9 levels.Conclusions: The preoperative CA19-9 level is an independent risk factor affecting the prognosis of patients with one small HCC, especially among the AFP-negative patients, and should be given full attention in clinical practice.

关键词： small hepatocellular carcinoma early recurrence nomogram CA19-9

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Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition

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Bioactive Materials 2021年第11期6卷 3744-3755页

作者： Qingqing Xiong Yang Bai Run Shi Jian Wang Weiguo Xu Mingming Zhang Tianqiang Song Department of Hepatobiliary Cancer Liver Cancer CenterTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin300060PR China Tianjin Key Laboratory of Biomedical Materials Institute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300192PR China Faculty of Medicine Ludwig-Maximilians-Universität MünchenMünchenD-80333Germany Department of Immunology Tianjin Medical University Cancer Institute&HospitalTianjin300060PR China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022PR China Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine Cangzhou061001PR China

Chemotherapy,as one of the most commonly used treatment modalities for cancer therapy,provides limited benefits to hepatoma patients,owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma.Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA-miR-122 for enhancing chemo-therapeutic efficacy in hepatoma.Herein,a cyclodextrin-cored star copolymer nanoparticle system(sCDP/DOX/miR-122)is constructed to co-deliver miR-122 with doxorubicin(DOX)for hepatoma therapy.In this nanosystem,miR-122 is condensed by the outer cationic poly(2-(dimethylamino)ethyl methacrylate)chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities,endowing a sequential release manner of miR-122 and DOX.The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity,but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression,which realizes synergistic performance on cell inhibition.Moreover,sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone,indicating its great promising in hepatoma therapy.

关键词： Cyclodextrin-based star copolymer nanoparticle miR-122 Doxorubicin Sequential release Hepatoma chemotherapy

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Modified Blumgart anastomosis without pancreatic duct-to-jejunum mucosa anastomosis for pancreatoduodenectomy：a feasible and safe novel technique

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Cancer Biology & Medicine 2018年第1期15卷 79-87页

作者： Xiaoqing Wang Yang Bai Mangmang Cui Qingxiang Zhang Wei Zhang Feng Fang Tianqiang Song Department of Hepatobiliary Oncology Tianjin Medical University Cancer Institute and Hospital National Clinical ResearchCenter for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for CancerTianjin 300060 China

Objective:This study proposed a modified Blumgart anastomosis(m-BA)that uses a firm ligation of the main pancreatic duct with a supporting tube to replace the pancreatic duct-to-jejunum mucosa anastomosis,with the aim of simplifying the complicated steps of the conventional BA(c-BA).Thus,we observe if a difference in the risk of postoperative pancreatic fistula(POPF)exists between the two methods.Methods:The m-BA anastomosis method has been used since 2010.From October 2011 to October 2015,147 patients who underwent pancreatoduodenectomy(PD)using BA in Tianjin Medical University Cancer Institute and Hospital were enrolled in this study.According to the type of pancreatojejunostomy(PJ),50 patients underwent m-BA and 97 received c-BA.The two patient cohorts were compared prospectively to some extent but not randomized,and the evaluated variables were operation time,the incidence rate of POPF,and other perioperative complications.Results:The operation time showed no significant difference(P>0.05)between the two groups,but the time of duct-to-mucosa anastomosis in the m-BA group was much shorter than that in the c-BA group(P0.05),which means that the modified anastomosis method did not cause additional pancreatic leakage.The mean length of postoperative hospital stay of the m-BA group was 23 days,and that of the c-BA group was 22 days(P>0.05).Conclusions:Compared with the conventional BA,we suggest that the modified BA is a feasible,safe,and effective operation method for P J of PD with no sacrifice of surgical quality.In the multivariate analysis,we also found that body mass

关键词：胰腺修改技术安全结扎试管手术

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肝癌外科治疗策略的转变与挑战

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中华外科杂志 2021年第6期59卷 447-451页

作者：宋天强国家肿瘤临床医学研究中心天津医科大学肿瘤医院肝癌防治研究中心肝胆肿瘤科300060

肝细胞癌是我国乃至世界上发病率和死亡率较高的常见恶性肿瘤。由于其具有肿瘤异质性且易发生远处播散转移,患者的预后往往较差。目前,以根治性肝切除术为主的外科治疗仍是肝癌患者治疗的首选方案,但术后的高复发转移率仍然阻碍着患者... 详细信息

肝细胞癌是我国乃至世界上发病率和死亡率较高的常见恶性肿瘤。由于其具有肿瘤异质性且易发生远处播散转移,患者的预后往往较差。目前,以根治性肝切除术为主的外科治疗仍是肝癌患者治疗的首选方案,但术后的高复发转移率仍然阻碍着患者生存预后的改善。因此,在靶向免疫治疗时代,肝癌外科治疗策略的转变就显得尤为关键。本文聚焦新辅助治疗的定义、在肝癌中的可行性、评估标准等方面,旨在为今后肝癌外科治疗提供新的视角。

关键词：肝肿瘤外科手术新辅助治疗

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同时性结直肠癌肝转移的治疗策略

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中华肝胆外科杂志 2020年第10期26卷 725-729页

作者：宋天强天津医科大学肿瘤医院肝癌防治研究中心国家肿瘤临床医学研究中心天津市恶性肿瘤临床医学研究中心天津300060

同时性结直肠癌肝转移是指结直肠癌确诊前或确诊时发现的肝转移。与异时性肝转移相比,同时性肝转移患者的预后更差。同时性肝转移因需要面对原发灶和转移灶,所以在治疗方式和手术顺序上具有多样性,故在保证患者生存获益的前提下,合理的... 详细信息

同时性结直肠癌肝转移是指结直肠癌确诊前或确诊时发现的肝转移。与异时性肝转移相比,同时性肝转移患者的预后更差。同时性肝转移因需要面对原发灶和转移灶,所以在治疗方式和手术顺序上具有多样性,故在保证患者生存获益的前提下,合理的选择至关重要。因此本文从同时性结直肠癌肝转移的定义、不同病灶状态的策略选择、手术顺序的选择、最新手术技术的进展等方面做一综述和回顾,同时分享本中心的治疗经验。

关键词：结直肠肿瘤同时性肝转移治疗选择手术策略

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Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma

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Cancer Biology & Medicine 2019年第1期16卷 89-99页

作者： Lu Chen Xiangdong Tian Wenchen Gong Bo Sun Guangtao Li Dongming Liu Piao Guo Yuchao He Ziye Chen Yuren Xia Tianqiang Song Hua Guo Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was discussed.Methods: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by WB.Results: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated markers.Conclusions: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and invasion.Our study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

关键词： Periostin hepatoblastoma EMT MAPK/ERK

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Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2020年第1期5卷 340-358页

作者： Yuqing Cao Xiaoyu Wang tianqiang Jin Yu Tian Chaoliu Dai Crystal Widarma Rui song Feng Xu Department of General Surgery Shengjing Hospital of China Medical University110004 ShenyangChina College of Life and Health Science Northeastern University110819 ShenyangChina Lawrence D.Longo MD Center for Perinatal BiologyDepartment of Basic SciencesLoma Linda University School of MedicineLoma LindaCA 92350USA

Recent studies have demonstrated the potential of natural killer(NK)cells in immunotherapy to treat multiple types of cancer.NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex.The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers.NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy.The effector role of these cells is reliant on the balance of inhibitory and activating signals.Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation.Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment;this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers.Accordingly,this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function,as well as their potential application in tumor immunotherapy.

关键词： immunotherapy killer cancer

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肝癌新辅助治疗的热点与经验分享

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肝癌电子杂志 2023年第1期10卷 53-56页

作者：宋天强天津医科大学肿瘤医院肝胆肿瘤科天津300060

研究显示手术切除超出米兰标准的肝癌可带来更多的生存获益,中国2022版原发性肝癌诊疗规范也推荐手术治疗适用于Ⅰa~Ⅱa期肝癌患者,即便Ⅱb~Ⅲa期也有部分患者适合手术。但是术后复发率高严重影响手术的效果,因此肝癌术后的辅助治疗一... 详细信息

研究显示手术切除超出米兰标准的肝癌可带来更多的生存获益,中国2022版原发性肝癌诊疗规范也推荐手术治疗适用于Ⅰa~Ⅱa期肝癌患者,即便Ⅱb~Ⅲa期也有部分患者适合手术。但是术后复发率高严重影响手术的效果,因此肝癌术后的辅助治疗一直是研究的热点。随着靶向免疫治疗的普及和疗效的进一步确定,肝癌的新辅助治疗逐渐成为研究的热点。从其他癌种的经验借鉴,新辅助治疗理论上是可行的,特别是结合免疫治疗的新辅助治疗较辅助治疗有更大的优势。新辅助治疗的适应人群、方案的选择,疗程的长短、疗效的评价指标等都是目前面临的问题。本文在此逐一进行阐述,以期引起更多学者对肝癌新辅助治疗的关注和研究,为今后肝癌新辅助治疗带来更多的证据。

关键词：肝癌辅助治疗新辅助治疗

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