scholarly journals Identification and validation of AKR1C1/2/3 as hepatocellular carcinoma risk modules via an integrated strategy

2020 ◽  
Author(s):  
Mingxing Xu ◽  
Yuesi Zhong ◽  
Fangji Yang ◽  
Kai Liu ◽  
Baoding Zhuang ◽  
...  

Abstract Background The human aldo-keto reductase 1 (AKR1) C family comprises four enzymes, AKR1C1–AKR1C4. Lots of studies have investigated the function of AKR1Cs in tumors, however little is known in hepatocellular carcinoma (HCC). Methods Public databases were used to explore expression and role of AKR1Cs in HCC. Meanwhile, data of 134 HCC patients from Firebrowse website was used for validation. Results The results revealed that AKR1Cs expression was negatively correlated with the infiltration level of CD4+ T cells. Overexpression of AKR1C1/2/3 was significantly associated with tumor stage and pathological grade. Moreover, higher mRNA expression of AKR1C1/2/3 was related with shorter overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS). Multivariate Cox regression analysis showed that AKR1C1/2/3 could be significant risk factors for HCC patients. Additionally, genetic alterations of AKR1Cs can significantly affect patient OS and PFS, and expression of AKR1Cs was linked to functional networks involving oxidation-reduction process, cellular hormone metabolic process and organic hydroxy compound metabolic process, as well as retinol metabolism, steroid hormone biosynthesis, metabolic pathway and fatty acid degradation pathways. Conclusions In conclusion, we successfully elaborated the relationship between AKR1Cs expression and immune infiltrations, and identified AKR1C1/2/3 could be novel prognostic biomarkers for HCC patients.

2019 ◽  
Author(s):  
Jianyong Lei ◽  
LN Yan ◽  
DJ Li ◽  
WT Wang

Abstract Aim: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 patients with small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, they were divided into the liver resection group (72 patients) and the RFA group (50 patients). Result : In comparison with the RFA group, the resection group had a longer operative time, and greater intra-operative blood loss (P<0.01), more hepatic inflow occlusion , and longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that resection or RFA was not a significant risk factor for overall or tumor-free survival for HCC. Conclusions : For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes, and RFA can be considered for wide application, especially for central cases.


2019 ◽  
Author(s):  
Jianyong Lei ◽  
LN Yan ◽  
DJ Li ◽  
WT Wang

Abstract Background: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 cases of small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, the patients were divided into liver resection (72 patients) and RFA (50 patients) groups. Result: In comparison with the RFA group, the resection group had a longer operative time, greater intraoperative blood loss (P<0.01), more hepatic inflow occlusion, and a longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that neither resection nor RFA was a significant risk factor for overall or tumor-free survival in HCC. Conclusions: For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes than resection and can be considered for wide application, especially for central-location cases.


2019 ◽  
Author(s):  
Jianyong Lei ◽  
LN Yan ◽  
DJ Li ◽  
WT Wang

Abstract Aim: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 patients with small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, they were divided into the liver resection group (72 patients) and the RFA group (50 patients). Result: In comparison with the RFA group, the resection group had a longer operative time, and greater intra-operative blood loss (P<0.01), more hepatic inflow occlusion, and longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that resection or RFA was not a significant risk factor for overall or tumor-free survival for HCC. Conclusions: For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes, and RFA can be considered for wide application, especially for central cases.


2019 ◽  
Author(s):  
Jianyong Lei ◽  
Yan Lunan ◽  
Li Dajiang ◽  
Wang Wentao

Abstract Aim: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 patients with small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, they were divided into the liver resection group (72 patients) and the RFA group (50 patients). Result: In comparison with the RFA group, the resection group had a longer operative time, and greater intra-operative blood loss (P<0.01), more hepatic inflow occlusion , and longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that resection or RFA was not a significant risk factor for overall or tumor-free survival for HCC. Conclusions: For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes, and RFA can be considered for wide application, especially for central cases.


2019 ◽  
Author(s):  
Jianyong Lei ◽  
LN Yan ◽  
DJ Li ◽  
WT Wang

Abstract Aim The goal of this study is to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5cm). Patients and methods We retrospectively collected 122 patients with small solitary HCC treated at our center, with diameters in the range of 3-5cm. According to the treatment program received at our center, they are divided into the liver resection group (72 cases) and the RFA group (50 cases). Result In comparison with the RFA group, the resection group requires a longer operative time, and the intra-operative blood loss is more (P<0.01); there is also more hepatic inflow occlusion, and the postoperative days of hospital stay are significantly longer (P<0.01). The 1-, 3-, and 5- year expected overall survival rates and tumor-free survival rates are comparable between two groups. Cox regression analysis showed that resection or RFA was not a significant risk factor for overall or tumor-free survival for HCC. Conclusions For solitary HCC of 3-5cm, RFA can achieve better hospital clinical results and similar long-term outcome, and RFA can be considered for wide application especially for central cases.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 444-444
Author(s):  
Dimitrios Makrakis ◽  
Daniel Castellano ◽  
Ivan de Kouchkovsky ◽  
Joseph J. Park ◽  
Mehmet Asim Bilen ◽  
...  

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 475-475
Author(s):  
Ryo Kanata ◽  
Masato Ozaka ◽  
Seita Kataoka ◽  
Kazunaga Ishigaki ◽  
Ikuhiro Yamada ◽  
...  

475 Background: In Japan, adjuvant chemotherapy with S-1 for 6 months is standard care for resected pancreatic cancer. However, the efficacy of chemotherapy for recurrent pancreatic cancer(RPC) after adjuvant S-1 chemotherapy is not well evaluated. Methods: Medical records were retrospectively reviewed for consecutive patients who had RPC after adjuvant S-1 treatment and received chemotherapy between April 2013 and July 2016. Recurrence free interval (RFI) was defined as the interval from adjuvant S-1 initiation to cancer recurrence. Overall survival (OS) and progression free survival (PFS) after 1st line chemotherapy for RPC were compared between patients with RFIs of shorter than 6 month (Group S) and longer than 6 months (Group L). Results: In the 53 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 5.1 months, and the median RFI was 8.3 months. After recurrence, they received Gemcitabine alone (20 patients), Gemcitabine+nab-paclitaxel (28 patients), modified FOLFIRINOX (one patient), and other regimen (4 patients). In all patients, the median PFS was 7.3 months and the median OS was 14.8 months. When compered in two groups (group S and group L), median OS in group S and group L was 6.7 months (95% confidence interval(CI): 4.2-12.9) and NA (95% CI: 13 months-NA) , respectively (p < 0.001), and median PFS was 3.8 months (95%CI: 2.5-9.1) and 7.3 months (95%CI: 3.9-15.3), respectively (p = 0.11). Multivariate Cox regression analysis revealed CEA < 4.0 mg/dl before chemotherapy and an RFI of ≥ 6 months were significantly associated with longer survival. Conclusions: These data suggest that RFI < 6 months is a surrogate marker for a poor prognosis in patients with RPC.


2020 ◽  
Author(s):  
Xiao-Yan Meng ◽  
Xiu-Ping Zhang ◽  
Hong-Qian Wang ◽  
Weifeng Yu

Abstract Background Whether anesthesia type is associate with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P=0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA has better survival outcomes compare to INHA in HCC patients with PVTT. Future prospective researches are urgent to verify this difference and figure out underlying causes of it.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16574-e16574
Author(s):  
Wei Peng ◽  
Jianhong Liu ◽  
Xiaorong Zhou ◽  
Hong Fan ◽  
Jianwei Lu ◽  
...  

e16574 Background: Emerging reports demonstrated that PIWI-interacting RNAs (piRNAs) played an indispensable role in tumorigenesis. However, it still remains elusive whether piR-1245 in gastric juice specific in stomach could be employed as a biomarker for gastric cancer (GC). The present work is aiming at exploring the possibility of piR-1245 in gastric juice as a potential marker to judge for diagnosis and prognosis of gastric cancer. Methods: Gastric juice was collected from 66 GC patients and 66 healthy individuals. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was employed to measure the levels of piR-1245 expression. Then, the pattern of piR-1245 expression in gastric juice was determined between GC patients and healthy individuals. A receiver operating characteristic (ROC) curve was constructed for distinguishing GC from healthy individuals. Results: Gastric juice piR-1245 levels in GC were higher than those of controls (P < 0.0001). The value of area under ROC (AUC) was 0.885 (sensitivity, 90.9%; specificity, 74.2%; 95% confidence interval, 0.8286 to 0.9414). High gastric juice piR-1245 expression was signally correlated with tumor size (P = 0.013) and TNM stage (P = 0.001). GC patients with high piR-1245 expression in gastric juice exerted a poorer overall survival (OS) (P = 0.0152) and progression-free survival (PFS) (P = 0.013). COX regression analysis verified that gastric juice piR-1245 expression was an independent prognostic risk variable for OS (P < 0.05). Conclusions: The current study suggested that piR-1245 in gastric juice had the potential to be a useful biomarker for GC detection and prognosis prediction.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Zhang ◽  
Lei Yang ◽  
Jia Shi ◽  
Yunfei Lu ◽  
Xiaorong Chen ◽  
...  

Objective. This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. Methods. Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. Results. CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P<0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P<0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P=0.025 and P<0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P=0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P<0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC=0.683). Conclusion. Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.


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