scholarly journals The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma

2018 ◽  
Vol 52 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Yangkyu Lee ◽  
Hyunjin Park ◽  
Hyejung Lee ◽  
Jai Young Cho ◽  
Yoo-Seok Yoon ◽  
...  
2020 ◽  
Author(s):  
Hongzhi Liu ◽  
Yuan Yang ◽  
Chuanchun Chen ◽  
Lei Wang ◽  
Qizhen Huang ◽  
...  

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary HBV-related HCC. Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm intervals. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). Results There are 8 dichotomy, 8 trichotomy and 14 inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. After reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), Microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fuqun Wei ◽  
Qizhen Huang ◽  
Yang Zhou ◽  
Liuping Luo ◽  
Yongyi Zeng

Abstract Background Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial. Methods A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3. Results There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group. Conclusion Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ji Li ◽  
Chen Zhu ◽  
Peipei Yue ◽  
Tianyu Zheng ◽  
Yan Li ◽  
...  

Abstract Background Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms. Methods Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently. Results High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop. Conclusions Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism–signaling target combined therapy.


Author(s):  
Andreas Schmidt ◽  
Angela Armento ◽  
Ovidio Bussolati ◽  
Martina Chiu ◽  
Verena Ellerkamp ◽  
...  

Abstract Purpose Glutamine plays an important role in cell viability and growth of various tumors. For the fetal subtype of hepatoblastoma, growth inhibition through glutamine depletion was shown. We studied glutamine depletion in embryonal cell lines of hepatoblastoma carrying different mutations. Since asparagine synthetase was identified as a prognostic factor and potential therapeutic target in adult hepatocellular carcinoma, we investigated the expression of its gene ASNS and of the gene GLUL, encoding for glutamine synthetase, in hepatoblastoma specimens and cell lines and investigated the correlation with overall survival. Methods We correlated GLUL and ASNS expression with overall survival using publicly available microarray and clinical data. We examined GLUL and ASNS expression by RT-qPCR and by Western blot analysis in the embryonal cell lines Huh-6 and HepT1, and in five hepatoblastoma specimens. In the same cell lines, we investigated the effects of glutamine depletion. Hepatoblastoma biopsies were examined for histology and CTNNB1 mutations. Results High GLUL expression was associated with a higher median survival time. Independent of mutations and histology, hepatoblastoma samples showed strong GLUL expression and glutamine synthesis. Glutamine depletion resulted in the inhibition of proliferation and of cell viability in both embryonal hepatoblastoma cell lines. ASNS expression did not correlate with overall survival. Conclusion Growth inhibition resulting from glutamine depletion, as described for the hepatoblastoma fetal subtype, is also detected in established embryonal hepatoblastoma cell lines carrying different mutations. At variance with adult hepatocellular carcinoma, in hepatoblastoma asparagine synthetase has no prognostic significance.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1615
Author(s):  
Ines P. Nearchou ◽  
Hideki Ueno ◽  
Yoshiki Kajiwara ◽  
Kate Lillard ◽  
Satsuki Mochizuki ◽  
...  

The categorisation of desmoplastic reaction (DR) present at the colorectal cancer (CRC) invasive front into mature, intermediate or immature type has been previously shown to have high prognostic significance. However, the lack of an objective and reproducible assessment methodology for the assessment of DR has been a major hurdle to its clinical translation. In this study, a deep learning algorithm was trained to automatically classify immature DR on haematoxylin and eosin digitised slides of stage II and III CRC cases (n = 41). When assessing the classifier’s performance on a test set of patient samples (n = 40), a Dice score of 0.87 for the segmentation of myxoid stroma was reported. The classifier was then applied to the full cohort of 528 stage II and III CRC cases, which was then divided into a training (n = 396) and a test set (n = 132). Automatically classed DR was shown to have superior prognostic significance over the manually classed DR in both the training and test cohorts. The findings demonstrated that deep learning algorithms could be applied to assist pathologists in the detection and classification of DR in CRC in an objective, standardised and reproducible manner.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liang Hong ◽  
Yu Zhou ◽  
Xiangbang Xie ◽  
Wanrui Wu ◽  
Changsheng Shi ◽  
...  

Abstract Background Cumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear. Methods Molecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature. Results We identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature. Conclusions Findings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.


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