Predictive Value of The G1–G6 Transcriptomic Molecular Classification of Hepatocellular Carcinoma for its Biological Behavior and Clinicopathological Features in China

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a large number of genetic alterations are involved in the carcinogenetic process. A G1–G6 transcriptomic classification was previously proposed in a French study, and Korean and Singaporean groups indicated its potential application in Asian HCC patients. However, the genomic profiles of Chinese patients are distinct from patients of other regions, and therefore the suitability of this method in Chinese HCC patients has remained unknown.Materials/Methods: In this study, we tested the transcriptomic group classification from the French cohort on a cohort of HCC patients from China. a total of 107 HCC cases from China were selected for the G1–G6 transcriptomic molecular classification. The correlation between the G1–G6 molecular classification and clinicopathological features were analyzed. RNA sequencing and bioinformatics analysis were performed to screen related targets and molecular signaling pathways.Results: We investigated the G1–G6 signatures in 107 Chinese HCC patients. HCC cases from China (n=107) were distributed as follows: G1 (17.76%), G2 (1.87%), G3 (18.69%), G4 (9.35%), G5 (23.36%), and G6 (28.97%) groups. We observed concordance between the genetic profiles and clinical features of Chinese HCC patients and French HCC patients. We found that the G1–G3 subgroups were associated with high serum alpha-fetoprotein (AFP) level, high copy number of hepatitis B virus (HBV) DNA, complex histopathological structure, macrovascular invasion, negative or weak Hep-Par1 expression, programmed death-ligand 1 expression, and liver cancer stemness. The G1 subgroup was mainly related to liver cancer stemness, and G3 subgroup showed the worst prognosis. The G5 and G6 subgroups were associated with activation of the Wnt/β-catenin pathway. Compared with the G1–G4 group, the G1–G3 group showed significantly higher expression levels of regenerating family member 1 beta (REG1B), regenerating family member 3 gamma (REG3G), and inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), and enriched calcium signaling pathway.Conclusions: Our results clarify the correlation between G1–G6 molecular classification and molecular markers and molecular signaling pathways in the Chinese HCC population and initially established a link between the phenotype and molecular characteristics. This study enhances our understanding of the heterogenicity of China HCC and indicates that the G1–G6 signatures can be used to identify potential therapeutic biomarkers against HCC patients in China.

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High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms20030581 ◽

2019 ◽

Vol 20 (3) ◽

pp. 581 ◽

Cited By ~ 7

Author(s):

Hyuk Moon ◽

Kyungjoo Cho ◽

Sunyeong Shin ◽

Do Kim ◽

Kwang-Hyub Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Fibrosis ◽

Liver Cancer ◽

Signaling Pathways ◽

Signaling Pathway ◽

Genetic Alterations ◽

Molecular Signaling ◽

Fibrotic Liver ◽

Molecular Signaling Pathways ◽

End Stage

Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, making up about 80% of cases. Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for HCC. A fibrotic liver typically shows persistent hepatocyte death and compensatory regeneration, chronic inflammation, and an increase in reactive oxygen species, which collaboratively create a tumor-promoting microenvironment via inducing genetic alterations and chromosomal instability, and activating various oncogenic molecular signaling pathways. In this article, we review recent advances in fields of liver fibrosis and carcinogenesis, and consider several molecular signaling pathways that promote hepato-carcinogenesis under the microenvironment of liver fibrosis. In particular, we pay attention to emerging roles of the Hippo-YAP/TAZ signaling pathway in stromal activation, hepatic fibrosis, and liver cancer.

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Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

Medical Sciences ◽

10.3390/medsci9010016 ◽

2021 ◽

Vol 9 (1) ◽

pp. 16

Author(s):

Renato Francesco Maria Scalise ◽

Rosalba De Sarro ◽

Alessandro Caracciolo ◽

Rita Lauro ◽

Francesco Squadrito ◽

...

Keyword(s):

Myocardial Infarction ◽

Signaling Pathways ◽

Ventricular Dysfunction ◽

Healing Process ◽

Molecular Signaling ◽

Cellular Processes ◽

Molecular Signaling Pathways ◽

Fibrotic Scar ◽

Life Threatening

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

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Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis

BMC Gastroenterology ◽

10.1186/s12876-020-01586-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chih-Wen Lin ◽

Tsung-Chin Wu ◽

Hung-Yu Lin ◽

Chao-Ming Hung ◽

Pei-Min Hsieh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Propensity Score ◽

Propensity Score Matching ◽

Surgical Resection ◽

Disease Free Survival ◽

Clinicopathological Features ◽

Free Survival ◽

Before And After ◽

Disease Free

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

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Revealing the molecular signaling pathways of mucus stasis in cystic fibrosis

Journal of Clinical Investigation ◽

10.1172/jci131652 ◽

2019 ◽

Vol 129 (10) ◽

pp. 4089-4090 ◽

Cited By ~ 3

Author(s):

Susan E. Birket ◽

Steven M. Rowe

Keyword(s):

Cystic Fibrosis ◽

Signaling Pathways ◽

Molecular Signaling ◽

Molecular Signaling Pathways

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Knowledge of the Molecular Signaling Pathways Improves the Chances of Treatment of Gastrointestinal Stromal Tumors

Cancer Studies and Molecular Medicine - Open Journal ◽

10.17140/csmmoj-2-109 ◽

2015 ◽

Vol 2 (1) ◽

pp. 69-71

Author(s):

Joana Espiga de Macedo ◽

Keyword(s):

Signaling Pathways ◽

Gastrointestinal Stromal Tumors ◽

Molecular Signaling ◽

Stromal Tumors ◽

Molecular Signaling Pathways

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Transcriptome dynamics in early in vivo developing and in vitro produced porcine embryos

10.21203/rs.3.rs-73275/v2 ◽

2020 ◽

Author(s):

Vera A van der Weijden ◽

Meret Schmidhauser ◽

Mayuko Kurome ◽

Johannes Knubben ◽

Veronika L Flöter ◽

...

Keyword(s):

Signaling Pathways ◽

Early Stage ◽

Developmental Competence ◽

Molecular Signaling ◽

Developmental Potential ◽

Stage Of Development ◽

Molecular Signaling Pathways ◽

Canonical Pathways

Abstract Background: The transcriptional changes around the time of embryonic genome activation in pre-implantation embryos indicate that this process is highly dynamic. In vitro produced porcine blastocysts are known to be less competent than in vivo developed blastocysts. To understand the conditions that compromise developmental competence of in vitro embryos, it is crucial to evaluate the transcriptional profile of porcine embryos during pre-implantation stages. In this study, we investigated the transcriptome dynamics in in vivo developed and in vitro produced 4-cell embryos, morulae and hatched blastocysts.Results: In vivo developed and in vitro produced embryos displayed largely similar transcriptome profiles during development. Enriched canonical pathways from the 4-cell to the morula transition that were shared between in vivo developed and in vitro produced embryos included oxidative phosphorylation, tRNA charging, and EIF2 signaling. The shared canonical pathways from the morula to the hatched blastocyst transition were 14-3-3-mediated signaling, signaling of Rho family GTPases, and NRF2-mediated oxidative stress response. The in vivo developed and in vitro produced hatched blastocysts were compared to identify molecular signaling pathways indicative of lower developmental competence of in vitro produced hatched blastocysts. A higher metabolic rate and expression of the arginine transporter SLC7A1 were found in in vitro produced hatched blastocysts.Conclusions: Our findings suggest that embryos with compromised developmental potential are arrested at an early stage of development, while embryos developing to the hatched blastocyst stage display largely similar transcriptome profiles, irrespective of the embryo source. The hatched blastocysts derived from the in vitro fertilization-pipeline showed an enrichment in molecular signaling pathways associated with lower developmental competence, compared to the in vivo developed embryos.

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