肝癌切除术后的长间隔与短间隔随访:一项回顾性队列研究

背景与目的由于缺乏证据证明肝细胞癌(hepatocellular carcinoma,HCC)切除术后的最佳随访间隔,术后患者接受随访的平均时间间隔不同。我们的目的是比较长间隔随访和短间隔随访与生存和复发的相关性在不同风险分层肝癌患者中的差异。方法我们在2007年至2014年期间进行了一项回顾性队列研究。共有1227例巴塞罗那临床肝癌分期A期或B期的患者接受了根治性切除术。根据最小绝对收缩和选择操作算法为基础的预后因素分析,我们将患者分层为有低风险(n=865)或高风险(n=362)早期复发(切除术后2年内)的2组。根据切除术后2年内的随访情况,患者进一步分为长间隔(每4–6个月)随访和短期间隔(每2–4个月)随访的亚组(低风险,长期vs.短期:n=390 vs. n=475;高风险,长期vs.短期:n=149 vs. n=213)。结果不管在低风险[风险比(hazard ratio,HR)=1.152;95%置信区间(confidenceinterval,CI):0.720–1.843]还是高风险(HR=1.213;95%CI:0.702–2.094)患者中,短间隔随访没有延长患者的总生存期。401例患者出现早期复发。在高风险患者中,与长间隔随访组相比,短间隔组肝内复发肿瘤较小(2.6 cm vs. 3.5 cm,P=0.045)。但是,对于巴塞罗临床肝癌分期0/A期,长间隔与短间隔随访不管在低风险还是高风险患者中复发率(63.1%vs. 68.2%,P=0.580;31.3%vs. 41.5%,P=0.280)差异均无统计学意义。类似的,根治性切除术后,长间隔或短间隔随访分别在低风险和高风险患者中的复发率(34.5%vs. 39.7%,P=0.430;14.6%vs. 20.3%,P=0.388)差异也均无统计学意义。结论对于巴塞罗那临床肝癌分期A期或B期的患者,在接受了根治性切除术后的前2年内,将随访时间从4–6月缩短为2–4个月并不能增加根治性切除术的成功率或延长患者生存时间。

Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif chemokine receptor 4

Background:We previously found that overexpression of the gene known as amplified in breast cancer 1(AIB1)was associated with lymph node metastasis and poor prognosis in patients with lung adenocarcinoma.However,the role of AIB1 in that malignancy remains unknown.The present study aimed to investigate the function of AIB1 in the process of lung adenocarcinoma cell metastasis.Methods:A series of in vivo and in vitro assays were performed to elucidate the function of AIB1,while real-time PCR and Western blotting were utilized to identify the potential downstream targets of AIB1 in the process of lung adenocarcinoma metastasis.Rescue experiments and in vitro assays were performed to investigate whether the invasive-ness of AIB1-induced lung adenocarcinoma was mediated by C-X-C motif chemokine receptor 4(CXCR4).Results:The ectopic overexpression of AIB1 in lung adenocarcinoma cells substantially enhanced cell migration and invasive abilities in vitro and tumor metastasis in vivo,whereas the depletion of AIB1 expression substantially inhibited lung adenocarcinoma cell migration and invasion.CXCR4 was identified as a potential downstream target of AIB1 in lung adenocarcinoma.The knockdown of AIB1 greatly reduced CXCR4 gene expression at both the transcription and protein levels,whereas the knockdown of CXCR4 in cells with AIB1 ectopic overexpression diminished AIB1-induced migration and invasion in vitro and tumor metastasis in vivo.Furthermore,we found a significant positive association between the expression of AIB1 and CXCR4 in lung adenocarcinoma patients(183 cases),and the co-overexpression of AIB1 and CXCR4 predicted the poorest prognosis.Conclusions:These findings suggest that AIB1 promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by upregulating CXCR4 and that it might be usable as a novel prognostic marker and/or therapeutic target for this disease.

不可切除肝内胆管细胞癌的转化治疗

肝内胆管细胞癌(ICC)是常见的肝脏原发恶性肿瘤之一,起源于肝内胆管分支衬覆上皮细胞,以腺癌最为多见。2020年统计约有906000例新发原发性肝癌,其中ICC占10%~15%,即9.1~13.6万例[1]。ICC的发病率在全球范围内呈上升趋势,欧美国家的发病率较低,但在泰国和中国等地区发病较高[2]。ICC的危险因素包括肝硬化、乙型/丙型病毒性肝炎、饮酒、糖尿病、肥胖、吸烟、非酒精性脂肪性肝炎和肝吸虫感染,以及胆道疾病,如原发性硬化性胆管炎、肝内胆管结石、先天性胆管扩张症、Caroli病和炎症性肠病等[3]。

Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma

Background and Aims:Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma(HCC)patients while the underlying mechanism of metastasis remains elusive.In our study,procollagen-lysine,2-oxoglutarate 5-dioxygenase 2(PLOD2)was shown to be involved in the process of metastasis in HCC.Methods:The Cancer Genome Atlas(TCGA)database and HCC tissue microarrays were used to evaluate the expression of genes.In vitro migration,invasion,in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC.RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells.A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5(IRF5).Results:The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues,and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients.In vitro experiments,knockdown of PLOD2 reduced the migration and invasion of human HCC cells.Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model.Baculoviral IAP repeat containing 3(BIRC3)was proven to be the downstream factor of PLOD2 in human HCC cells.In addition,PLOD2 was transcriptionally regulated by IRF5 in HCC cells.Conclusions:High expression of PLOD2 was regulated by IRF5,which was correlated with the poor survival of HCC patients.PLOD2 enhanced HCC metastasis via BIRC3,suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.

Long- versus short-interval follow-up after resection of hepatocellular carcinoma: a retrospective cohort study

Background:Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma(HCC)resection because of limited evidence regarding the optimal interval.We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients.Methods:We performed a retrospective cohort study between 2007 and 2014.In total,1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low(n=865)or high(n=362)risk of early recurrence(within the first 2 years after resection)based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm.Patients were further classified into long-interval(every 4-6 months)and short-interval(every 2-4 months)follow-up subgroups based on follow-up within 2 years after resection(low risk,long vs.short:n=390 vs.n=475;high-risk,long vs.short:n=149 vs.n=213).Results:The short-interval follow-up did not prolong overall survival in either the low-risk(hazard ratio[HR]=1.152;95%confidence interval[CI]0.720-1.843)or high-risk(HR=1.213;95%CI 0.702-2.094)patients.Early recurrence occurred in 401 patients.For high-risk patients,the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group(2.6 vs.3.5 cm,respectively,P=0.045).However,no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long-and short-interval follow-up groups in either low-or high-risk patients(63.1%vs.68.2%,respectively,P=0.580;31.3%vs.41.5%,respec-tively,P=0.280).The rate of curative intent treatment for recurrence(34.5%vs.39.7%,respectively,P=0.430;14.6%vs.20.3%,respectively,P=0.388)was also similar between the follow-up groups for low-and high-risk patients.Conclusions:Shortening the postoperative follow-up interval from every 4-6 months to every 2-4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC.