肌少症预测肺癌患者预后的研究进展北大核心

肺癌是我国死亡率最高的恶性肿瘤。肌少症在肺癌患者中发病率较高,且近年来越来越多的研究显示肌少症对肺癌患者预后预测具有一定价值。本文就肌少症的诊断、肺癌与肌少症的关系以及肌少症对肺癌患者预后预测、干预治疗等方面的研究进行综述。     

肌少症对食管鳞癌术后复发患者放化疗不良反应及预后影响

目的 探讨基于定位CT分析肌少症对食管鳞癌术后复发患者放化疗期间不良反应及预后的影响。方法 回顾性分析2016—2017年于淮安市第一人民医院行放化疗的147例食管鳞癌术后局部复发患者,依据模拟定位CT勾画计算主动脉弓上缘水平横断面双侧胸肌面积（PMA）。PMA身高校正（PMA/身高²）得出胸肌指数（PMI）。将男女患者分别依据PMI三分位数分组,其中低PMI者（男性<11.55 cm²/m²,女性<8.69 cm²/m²）为肌少症组。比较肌少症组与非肌少症组患者治疗期间不良反应发生率及1年和3年总生存（OS）率的差异。结果 147例患者中49例（33.3%）存在肌肉减少,该类患者3‐4级不良反应发生率显著高于非肌少症患者（40.8%∶18.4%,P=0.005）。肌少症患者1年和3年OS（61.2%和10.2%）显著低于非肌少症患者（82.7%和28.6%）,差异具有统计学意义（P<0.001）,多因素分析证实肌少症是预测不良预后的独立危险因素（P<0.001）。结论 基于定位CT获得的PMI在诊断肌少症方面具有较好的临床价值,可能可以作为诊断肌少症的新工具。     

肌少症对老年肝癌术后恢复及预后的影响

目的:肌少症对老年肝癌术后恢复及预后的影响。方法:选取2015年1月至2017年12月收治的114例老年肝癌，根据有无合并肌少症，分为肌少症组（n=35）和非肌少症组（n=79）。比较两组患者的术后恢复及生存情况。结果:肌少症组总并发症发生率、住院时间和30 d再入院率均高于对照组，差异均有统计学意义（P＜0.05）。肌少症组中位生存时间为25.9个月，1年、2年、3年累积总生存率为74.3%、51.1%、24.5%，而非肌少症组中位生存时间为35.7个月，1年、2年、3年累积总生存率为87.3%、75.6%、49.4%，差异有统计学意义（P=0.004）。单因素分析结果显示，老年肝癌术后预后与Charlson合并症指数（CCI）、肌少症、巴塞罗那分期（BCLC）、甲胎蛋白、肿瘤大小、肿瘤个数、肿瘤分化程度、微血管侵犯（MVI）相关（P＜0.05）。Cox多因素分析结果显示，CCI、肌少症、BCLC分期、肿瘤个数、MVI是老年肝癌术后预后的独立危险因素（P＜0.05）。结论:肌少症会增加老年肝癌患者术后并发症发生率，延长住院时间，影响术后恢复，同时也会降低总生存率。     

肝细胞肝癌骨转移的研究进展

肝细胞肝癌（HCC）是我国发病率较高的恶性肿瘤,骨骼是HCC常见的肝外转移部位。HCC骨转移不仅严重影响患者生命质量且缩短生存时间,但其发生机制尚未完全明确。文章从HCC骨转移的临床特征、发生机制、预后影响因素及诊疗进展等方面进行综述,以期为临床诊疗提供新思路。     

驱动蛋白超家族在肝细胞癌中的作用及其机制和临床意义的研究进展

肝细胞癌（HCC）是转移性极高、预后极差的恶性肿瘤之一,寻找与其发生与发展密切相关的预后标志物和治疗靶点是提高HCC预后监测和治疗的关键。驱动蛋白超家族（KIF）在HCC组织中特异性高表达,并且这种异常表达可通过激活上皮间质转化（EMT）促进HCC转移,影响HCC的预后和药物治疗的疗效,提示KIF可能是HCC预后监测和治疗中极具前景的预后标志物和分子治疗靶点。阐明KIF在HCC转移、预后和治疗中的作用及其机制,以及其作为HCC预后标志物和分子治疗靶点的临床意义,对开发HCC的预后监测及靶向治疗新策略至关重要。     

循环肿瘤细胞在肝癌中的研究及应用进展

肝细胞癌（hepatocellular carcinoma，HCC）是全球范围内最常见的恶性肿瘤之一，发病率及死亡率高，预后差。影响预后的主要原因为早期诊断困难及术后易复发、转移。因此，HCC的早期诊断及术后监测对改善HCC患者的总体预后尤为重要。循环肿瘤细胞（circulating tumor cell，CTC）是存在于血液循环中的恶性肿瘤细胞，在肿瘤的侵袭、转移中发挥重要作用。CTC检测作为“液体活检”技术，能够实时重复监测外周血中的肿瘤细胞，在肿瘤早期诊断、术后动态监测及预后评价等方面具有巨大的临床应用价值。本文回顾了国内外CTC研究进展，对其检测方法及在HCC患者诊断、预后等方面的研究及临床应用等进行系统综述。      

白蛋白‐胆红素分级评估肝癌患者疗效和预后的 研究进展

肝细胞癌（HCC）是全球最常见的恶性肿瘤之一，而我国肝癌的发病率和死亡率均居世界首位。目前 HCC的治疗 手段多样，其中包括外科手术治疗（肝切除、肝移植）、局部消融治疗、介入治疗、放射治疗、免疫治疗、靶向治疗以及化疗等。但 这些治疗措施对患者的肝功能均有一定要求，因为各类治疗均可能对肝癌患者的肝功能带来损伤，而部分肝癌患者发现时已 处于晚期，本身即存在肝功能不全。因此，建立一个简单有效的可评估HCC患者肝功能的模型，以指导其临床疗效及预后是 非常必要的。Child⁃Pugh评分是目前临床上最常用的评估肝功能的方法，并被纳入BCLC分期系统指导HCC患者的临床治疗 和评估预后。但其包含的5个指标，白蛋白、总胆红素、肝性脑病、腹水和凝血酶原时间未区分权重大小，且腹水、肝性脑病的 主观性较强，此外白蛋白和腹水也是互相影响的因素，从而降低了评分的客观性和精确性。白蛋白⁃胆红素（ALBI）分级是近年 来提出的评估肝功能的新方法，仅包含白蛋白和胆红素两项客观指标，更简单客观。具体计算公式为 ALBI=（log10胆红素× 0.66）+（白蛋白×⁃0.085），根据得分将 HCC患者分为 3个等级，ALBI 1级：ALBI≤⁃2.60，ALBI 2级：⁃2.60⁃1.39，分级越高，肝功能越差。近年来，ALBI在评估HCC患者疗效和预后方面的作用已得到普遍验证。本文就ALBI分 级分别在经肝移植、肝切除、肝射频消融、肝动脉化疗栓塞及靶向、免疫治疗的HCC患者疗效和预后评估中的应用，以及ALBI 分级与其他分期系统联合评估HCC患者的预后等方面进行了综述。     

免疫检查点抑制剂治疗肝细胞癌的研究进展

肝癌的发病率及死亡率在全球恶性肿瘤中均位居前列。初诊的肝细胞癌（hepatocellular carcinoma，HCC）患者大多已处于晚期，失去手术根治的机会，全身治疗成为主要的治疗手段。随着免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）的出现，多种ICIs被批准用于晚期HCC患者，ICIs联合抗血管生成药物为主的靶向药物的治疗方案也被证实比ICIs单药效果更佳。但是，无论是单药ICIs还是联合治疗方案，多数患者仍不能从中获益。根据患者治疗的不同目标，通过肿瘤标记物选择不同的治疗方案是目前临床面临的挑战。本文对目前ICIs以及联合不同药物和局部治疗在HCC的临床研究进展、预测疗效和预后的生物标记物以及耐药性相关问题进行综述。      

环氧合酶-2与肝癌关系的研究进展

肝癌（HCC）是世界性疾病，其发病率和死亡率分别位居恶性肿瘤的第5位和第3位。2000年全球肝癌发病人数为56，4万，死亡54．9万；我国肝癌发病人数为30．6万，死亡30．0万。近几十年来全世界肝癌发病率、死亡率呈上升趋势。因此人们越来越重视对HCC的研究。但有限的治疗手段和治疗效果不理想及预后差促使人们寻找更有效的治疗方法。在这些研究中，近年来国外学者研究发现环氧合酶-2（COX-2）在肝癌及直肠癌中呈高表达，     

晚期肝细胞癌的系统治疗现状及研究进展

摘 要：肝细胞癌（hepatocellular carcinoma，HCC），是一种发病率和死亡率高、预后差且易复发和转移的消化系统恶性肿瘤。以靶向治疗和免疫治疗为主的系统治疗在晚期HCC一线治疗中疗效肯定。靶向治疗联合免疫治疗可有效延长患者生存期，改善预后，中药辅助治疗也在综合抗肿瘤治疗中发挥作用。病因治疗和新的抗HCC作用靶点也是肝细胞癌领域的研究热点。全文主要围绕晚期HCC的靶向治疗、免疫治疗等系统治疗以及病因和新作用靶点研究的现状及进展进行综述。     

黑色素瘤抗原A家族与肝细胞癌

黑色素瘤抗原A (MAGE-A)是一组肿瘤相关性抗原,主要表达于以黑色素瘤为主的多种恶性肿瘤组织中.肝细胞癌(HCC)是发生于肝脏的上皮性恶性肿瘤,患病率高,寻找有效的诊断和治疗方法成为极其迫切的任务.目前已证实MAGE-A基因在HCC组织中高表达,对HCC诊治及预后判断具有重要意义.     

Strategy and mechanism for the prevention of hepatocellular carcinoma: Phosphorylated retinoid X receptor α is a critical target for hepatocellular carcinoma chemoprevention

Hepatocellular carcinoma (HCC) is a major health care problem worldwide. The prognosis of patients with HCC is poor because even in the early stages when surgical treatment might be expected to be curative, the incidence of recurrence in patients with underlying cirrhosis is very high due to multicentric carcinogenesis. Therefore, strategies to prevent recurrence and second primary HCC are required to improve the prognosis. One of the most practical approaches to prevent the multicentric development of HCC is 'clonal deletion' therapy, which is defined as the removal of latent (i.e. invisible) (pre)malignant clones from the liver in a hypercarcinogenic state. Retinoids, a group of structural and functional analogs of vitamin A, exert their biological function primarily through two distinct nuclear receptors, retinoic acid receptors and retinoid X receptors (RXR), and abnormalities in the expression and function of these receptors are highly associated with the development of various cancers, including HCC. In particular, a malfunction of RXRα due to phosphorylation by the Ras–mitogen-activated protein kinase signaling pathway is profoundly associated with the development of HCC and thus may be a critical target for HCC chemoprevention. Acyclic retinoid, which has been clinically shown to reduce the incidence of a post-therapeutic recurrence of HCC, can inhibit Ras activity and phosphorylation of the extracellular signal-regulated kinase and RXRα proteins. In conclusion, the inhibition of RXRα phosphorylation and the restoration of its physiological function as a master regulator for nuclear receptors may be a potentially effective strategy for HCC chemoprevention and clonal deletion. Acyclic retinoid, which targets phosphorylated RXRα, may thus play a critical role in preventing the development of multicentric HCC. ( Cancer Sci 2009; 100: 369–374)     

Ethanol treatment of hepatocellular carcinoma: high potentials of low concentrations

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, which is associated with a very poor prognosis. A curative treatment is difficult to achieve and is only possible in a low number of patients. Therefore, many different therapeutic strategies have been developed as alternative treatment. Among these, percutaneous injection of high concentrations of ethanol (>50 mM) has been proven to be effective for the treatment of small HCC (less than 3 cm in diameter). However, the principal problem with using ethanol is its toxic effects on non-tumor cells adjacent to the tumor area. The objective of this review is to juxtapose the therapeutic potential of high and low concentrations of ethanol in the treatment of HCC, based on experimental studies obtained with the human hepatocellular tumor cell line (HepG2). They have shown that high concentrations of ethanol lead to necrosis, while low concentrations induce apoptosis due to activation of Fas-receptors. Triggering of apoptosis through Fas-receptors represents a mechanism of action different from that observed with high concentrations of ethanol, thus, reducing the complications that follow the inflammatory process due to necrosis. Therefore, the use of low concentrations of ethanol could be an effective treatment for HCC.     

MicroRNA in HCC: Biomarkers and Therapeutic Targets

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. At present, diagnostic methods such as imaging observation, serum testing and tissue biopsy, as well as treatment methods such as surgical resection, radiotherapy, and chemotherapy have certain limitations in clinical interventions for HCC due to the complex pathogenesis and drug resistance of liver cancer, which seriously affect the survival and prognosis of patients. As a large-scale cytokine, microRNA (miRNA) plays an important role in regulating various life activities of cells. Extensive evidence proved that certain miRNAs are specifically expressed in the tissues and blood of HCC patients, and some of them have been confirmed as important factors that can participate in the regulation of key signaling pathways in cancer cells. For this reason, these miRNAs have great potential in clinical diagnosis and treatment of HCC, and can improve the limitations of conventional diagnosis and treatment. Our paper reviews the research on miRNA biomarkers and targets in HCC in recent years, and aims to provide new ideas for the diagnosis and treatment of HCC.     

肝细胞癌根治术后早期复发及其时间点的研究进展

肝细胞癌是我国常见的恶性肿瘤之一,外科手术是目前治疗肝细胞癌最主要的方法,但手术后的高复发率是影响其预后的重要原因,也是目前亟待解决的关键临床问题.按照复发时间,可分为早期复发及远期复发.早期复发患者的预后较远期复发差,因此两种复发的鉴别对于外科决策来说至关重要,本文就肝细胞癌根治术后早期复发时间点的研究进展进行综述.     

肝癌新辅助治疗可行性的探讨

肝癌是我国乃至世界上发病率和病死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,肝癌患者的预后往往较差,但传统的干预治疗选择却较为有限。目前,以根治性肝切除术和肝移植术为首的外科治疗策略仍是肝癌患者治疗的首选方案,然而随着区域性、系统性治疗的发展,一定程度上增加了可行外科治疗的患者比例以及延长部分患者的生存预后。因此,在新时代下,肝癌外科治疗策略的转变就显得尤为关键。为了实施这种治疗概念并充分利用新辅助治疗策略的潜力,我们需要使用更多高级别的循证医学证据以指导治疗决策。     

High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential

We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non‐tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC‐related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis. © 2013 UICC     

Upregulation of phosphatidylinositol glycan anchor biosynthesis class C is associated with unfavorable survival prognosis in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor, and is the second highest cause of cancer-associated mortality, behind lung carcinoma. It is urgent to identify novel genes that can be used to confirm the diagnosis and prognosis of patients with HCC. The present study aimed to investigate the expression pattern of phosphatidylinositol glycan anchor biosynthesis class C (PIGC) in HCC and assess its clinical prognostic significance. Bioinformatics analyses were used to investigate PIGC mRNA expression levels in HCC and adjacent non-cancerous tissue samples. Furthermore, the present study detected the expression levels of PIGC protein in HCC and matched normal tissue samples via immunohistochemistry, and evaluated the prognostic significance of PIGC protein in HCC. The levels of PIGC mRNA and protein were found to be significantly higher in tissue from patients with HCC compared with non-cancerous liver tissue. The survival analysis showed that the expression levels of PIGC mRNA or protein were associated with the survival of patients with HCC. PIGC protein expression was significantly associated with Tumor-Node-Metastasis stage. A negative correlation between PIGC DNA methylation and mRNA expression was observed (Spearman r=−0.453). PIGC is an oncogene that is negatively regulated by DNA methylation, and high levels of PIGC mRNA or protein may predict an unfavorable prognosis in patients with HCC.     

Identification of heterogeneous nuclear ribonucleoprotein as a candidate biomarker for diagnosis and prognosis of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate. However, spliceosomal genes are still lacking in the diagnosis and prognosis of HCC.MethodsIdentification of differentially expressed genes (DEGs) was performed using the limma package in R software. Modules highly related to HCC were obtained by weighted gene co-expression network analysis (WGCNA), and the module genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The biomarker for diagnosing HCC was determined by receiver operating characteristic (ROC) curve analysis, and the effect of the biomarker in the diagnosis of HCC was evaluated by performing five-fold cross-validation with logistic regression. HCC specimens from preoperatively treated patients were tested for biomarker by real-time quantitative polymerase chain reaction (RT-qPCR). Kaplan-Meier analysis was used to assess the relationship between biomarker and patient survival. The role of biomarker was evaluated using ESTIMATE analysis in the tumor microenvironment.ResultsIn this study, 389 DEGs were screened out from three Gene Expression Omnibus (GEO) datasets. We also found that the turquoise module of 123 genes from The Cancer Genome Atlas (TCGA) data was the key module with the highest correlation with HCC traits. Then, 123 genes were analyzed using the KEGG enrichment pathway, and eight genes were found to be most significantly related to the spliceosome pathway. We selected 8 genes and 389 DEGs shared genes, and finally got the only gene, heterogeneous nuclear ribonucleoprotein (hnRNPU). The high expression of hnRNPU was associated with poor prognosis of HCC, and hnRNPU was a biomarker for diagnosing HCC. In the tissues of patients with excellent HCC treatment hnRNPU messenger RNA (mRNA) was lower than in the tissues of patients with poor HCC treatment. High expression of hnRNPU was significantly increased in HCC patients with low stromal (P<0.05), low immune (P<0.05), and low estimation scores (P<0.05), and with high tumor purity (P<0.05) and high malignant progression (P<0.05) of the HCC.ConclusionsThe hnRNPU gene identified in this study may become a new biomarker for the diagnosis and prognosis of HCC.     

索拉非尼治疗国人晚期肝细胞癌的临床研究进展

原发性肝癌, 主要是肝细胞癌（HCC）,是我国高发、常见的恶性肿瘤,晚期患者治疗棘手、预后恶劣。我国的HCC在发病原因、生物学行为、临床特征、治疗选择和预后上,都与西方国家明显不同,积极探索适合我国HCC患者合理规范的治疗具有重要意义。分子靶向药物索拉非尼作为口服多靶点多激酶抑制剂,经国际大型临床研究证实可以延长晚期HCC患者的生存期,在我国上市应用6年多,其疗效和安全性较好,但也存在一些问题。为了合理用药,进一步提高疗效,近年来,国内学者陆续开展了一系列索拉非尼单药、联合其他药物或手段治疗国人晚期HCC的临床研究和观察。本文拟对其相关研究进展进行综述和讨论,以提供临床参考。