Prognostic analysis of patients with combined hepatocellularcholangiocarcinoma after radical resection:A retrospective multicenter cohort study

BACKGROUND Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma.AIM To investigate overall survival(OS)and recurrence-free survival(RFS)after radical resection in patients with cHCC-CCA,and the clinicopathological factors affecting prognosis in two center hospitals of China.METHODS We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively.Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis.RESULTS Our study included 95 patients who received radical resection.The majority of these patients were male and 82.7%of these patients were infected with HBV.The mean tumor size was 4.5 cm,and approximately 40%of patients had more than one lesion.The median OS was 26.8(95%CI:18.5-43.0)mo,and the median RFS was 7.27(95%CI:5.83-10.3)mo.Independent predictors of OS were CA19-9≥37 U/mL(HR=8.68,P=0.002),Child-Pugh score>5(HR=5.52,P=0.027),tumor number>1(HR=30.85,P=0.002),tumor size and transarterial chemoembolization(TACE)after surgery(HR=0.2,P=0.005).CONCLUSION The overall postoperative survival of cHCC-CCA patients is poor,and most patients experience relapse within a short period of time after surgery.Preoperative tumor biomarker(CA19-9,alphafetoprotein)levels,tumor size,and Child-Pugh score can significantly affect OS.Adjuvant TACE after surgery prolongs RFS,suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.

Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is a malignancy found globally.Accumulating studies have shown that long noncoding RNAs(lncRNAs)play critical roles in HCC.However,the function of lncRNA in HCC remains poorly understood.AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms.METHODS We measured the expression of lncRNA W42 in HCC tissues and cells(Huh7 and SMMC-7721)by quantitative reverse transcriptase polymerase chain reaction.Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression.HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42.Cell functions were detected by cell counting Kit-8(CCK-8),colony formation,flow cytometry and Transwell assays.The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays.An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo.The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC.RESULTS In this study,we identified a novel lncRNA(lncRNA W42),and investigated its biological functions and clinical significance in HCC.LncRNA W42 expression was upregulated in HCC tissues and cells.Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC,and inhibited cell apoptosis.LncRNA W42 directly bound to DBN1 and activated the downstream pathway.LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo.The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times.CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42,which is upregulated in HCC,may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.

Long non-coding ribonucleic acid W5 inhibits progression and predicts favorable prognosis in hepatocellular carcinoma

BACKGROUND Accumulating evidence has revealed that several long non-coding ribonucleic acids(lncRNAs)are crucial in the progress of hepatocellular carcinoma(HCC).AIM To classify a long non-coding RNA,i.e.,lncRNA W5,and to determine the clinical significance and potential roles of lncRNA W5 in HCC.METHODS The results showed that lncRNA W5 expression was significantly downregulated in HCC cell lines and tissues.Analysis of the association between lncRNA W5 expression levels and clinicopathological features suggested that low lncRNA W5 expression was related to large tumor size(P<0.01),poor histological grade(P<0.05)and serious portal vein tumor thrombosis(P<0.05).Furthermore,Kaplan-Meier survival analysis showed that low expression of lncRNA W5 predicts poor overall survival(P=0.016).RESULTS Gain-of-loss function experiments,including cell counting kit8 assays,colony formation assays,and transwell assays,were performed in vitro to investigate thebiological roles of lncRNA W5.In vitro experiments showed that ectopic overexpression of lncRNA W5 suppressed HCC cell proliferation,migration and invasion;conversely,silencing of lncRNA W5 promoted cell proliferation,migration and invasion.In addition,acting as a tumor suppressor gene in HCC,lncRNA W5 inhibited the growth of HCC xenograft tumors in vivo.CONCLUSION These results showed that lncRNA W5 is down-regulated in HCC,and it may suppress HCC progression and predict poor clinical outcomes in patients with HCC.LncRNA W5 may serve as a potential HCC prognostic biomarker in addition to a therapeutic target.

Increased circulating level of interleukin-6 and CD8+T cell exhaustion are associated with progression of COVID-19

Background: Coronavirus disease 2019(COVID-19)is pandemic.It is critical to identify COVID-19 patients who are most likely to develop a severe disease.This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression.Methods:: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing,China from December 27,2019 to March 12,2020 were enrolled in this study and followed-up to March 16,2020.Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by theχ2 test or the Fisher exact test(categorical variables)and independent group t test or Mann–Whitney U test(continuous variables).The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19.Results: The mean incubation was 8.67(95%confidence interval,6.78–10.56)days.Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38(9.86–12.90)days.Compared to pneumonia-free patients,pneumonia patients were 16.5 years older and had higher frequencies of having hypertension,fever,and cough and higher circulating levels of neutrophil proportion,interleukin-6,low count(<190/µl)of CD8+T cells,and neutrophil/lymphocyte ratio.Thirteen patients deteriorated during hospitalization.Cox regression analysis indicated that older age and higher serum levels of interleukin-6,C-reactive protein,procalcitonin,and lactate at admission significantly predicted the progression of COVID-19.During hospitalization,circulating counts of T lymphocytes,CD4+T cells,and CD8+T cells were lower,whereas neutrophil proportion,neutrophil/lymphocyte ratio,and the circulating levels of interleukin-6,C-reactive protein,and procalcitonin were higher,in pneumonia patients than in pneumonia-free patients.CD8+lymphocyte count in pneumonia patients did not recover when discharged.Conclusions: Older age and higher levels of C-reactive protein,procalcitionin,interleukin-6,and lactate might predict COVID-19 progression.T lymphocyte,especially CD8+cell-mediated immunity is critical in recovery of COVID-19.This study may help in predicting disease progression and designing immunotherapy for COVID-19.

A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is the second most common primary hepatic malignancy that causes a poor survival.We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages.Methods:A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled.Subjects were followed for survival status until June 30,2020.A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model,and was then validated in the validation cohort.Results:The median age was 55 years.With a median follow-up of 50.4 months,337 patients died.The median survival was 11.6 months,with 1-,3-and 5-year survival rates of 48.3%,22.7%and 16.2%,respectively.Factors associated with overall survival were multiple tumors,lymph node involvement,vascular invasion,distant metastasis,decreased albumin,elevated lactate dehydrogenase(LDH),decreased iron,elevated fi-brinogen,elevated CA125 and elevated CA19-9.A nomo-gram predicting survival of ICC patients at the time of di-agnosis achieved a Harrel’s c-statistic of 0.758,significantly higher than the 0.582 of the TNM stage alone.Predicted median survivals of those within the low,mid and high-risk subgroups were 35.6,12.1 and 6.2 months,respectively.Conclusions:A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC.Further studies are needed to validate the prognostic capability of our new model.