A Transcriptomic Signature for Risk‐Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma

Wada, Yuma; Shimada, Mitsuo; Yamamura, Kensuke; Toshima, Takeo; Banwait, Jasjit K.; Morine, Yuji; Ikemoto, Tetsuya; Saito, Yu; Baba, Hideo; Mori, Masaki; Goel, Ajay

doi:10.1002/hep.31803

Cited by 16 publications

(8 citation statements)

References 55 publications

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“…found and verified that CENPW can be used as one of the gene markers associated with recurrence in patients with intrahepatic CHOL. 36 In liver cancer, knockdown of CENPW inhibited cell proliferation, migration, and invasion and induced G0/G1 phase arrest and apoptosis in liver cancer cells. 37 Overexpression of CENPW is associated with poor prognosis and may be a potential predictive biomarker for hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Yao

Liu

Tian

et al. 2022

Molecular Therapy - Oncolytics

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Section: Discussionmentioning

confidence: 99%

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Yao

Liu

Tian

et al. 2022

Molecular Therapy - Oncolytics

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“…Yuma Wada et al. 's research identified POC1A as a critical marker for predicting intra‐hepatic cholangiocarcinoma recurrence 14 . However, the correlation between POC1A and LUAD has not been extensively explored.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis

Li,

et al. 2024

J Cellular Molecular Medi

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Lung adenocarcinoma (LUAD) is characterized by a high incidence rate and mortality. Recently, POC1 centriolar protein A (POC1A) has emerged as a potential biomarker for various cancers, contributing to cancer onset and development. However, the association between POC1A and LUAD remains unexplored. We extracted The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) data sets to analyse the differential expression of POC1A and its relationship with clinical stage. Additionally, we performed diagnostic receiver operator characteristic (ROC) curve analysis and Kaplan–Meier (KM) survival analysis to assess the diagnostic and prognostic value of POC1A in LUAD. Furthermore, we investigated the correlation between POC1A expression and immune infiltration, tumour mutation burden (TMB), immune checkpoint expression and drug sensitivity. Finally, we verified POC1A expression using real‐time quantitative polymerase chain reaction (RT‐qPCR) and immunohistochemistry (IHC). Cell experiments were conducted to validate the effect of POC1A expression on the proliferation, migration and invasion of lung cancer cells. POC1A exhibited overexpression in most tumour tissues, and its overexpression in LUAD was significantly correlated with late‐stage presentation and poor prognosis. The high POC1A expression group showed lower levels of immune infiltration but higher levels of immune checkpoint expression and TMB. Moreover, the high POC1A expression group demonstrated sensitivity to multiple drugs. In vitro experiments confirmed that POC1A knockdown led to decreased proliferation, migration, and invasion of lung cancer cells. Our findings suggest that POC1A may contribute to tumour development by modulating the cell cycle and immune cell infiltration. It also represents a potential therapeutic target and marker for the diagnosis and prognosis of LUAD.

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“…CCAs are molecularly heterogeneous tumors, and this characteristic extends beyond their anatomical classification. Recent transcriptomic, genomic, proteogenomic and epigenomic analyses have identified different molecular subclasses indicative of potential carcinogenic mechanisms leading to CCA development [ 3 , 4 ]. The complex molecular profile of CCAs may underlie their high resistance to chemotherapy, targeted agents and immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming

Colyn

Álvarez‐Sola

Latasa

et al. 2022

J Exp Clin Cancer Res

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Background Cholangiocarcinoma (CCA) is still a deadly tumour. Histological and molecular aspects of thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats mimic those of human iCCA. Carcinogenic changes and therapeutic vulnerabilities in CCA may be captured by molecular investigations in bile, where we performed bile proteomic and metabolomic analyses that help discovery yet unknown pathways relevant to human iCCA. Methods Cholangiocarcinogenesis was induced in rats (TAA) and mice (JnkΔhepa + CCl4 + DEN model). We performed proteomic and metabolomic analyses in bile from control and CCA-bearing rats. Differential expression was validated in rat and human CCAs. Mechanisms were addressed in human CCA cells, including Huh28-KRASG12D cells. Cell signaling, growth, gene regulation and [U-13C]-D-glucose-serine fluxomics analyses were performed. In vivo studies were performed in the clinically-relevant iCCA mouse model. Results Pathways related to inflammation, oxidative stress and glucose metabolism were identified by proteomic analysis. Oxidative stress and high amounts of the oncogenesis-supporting amino acids serine and glycine were discovered by metabolomic studies. Most relevant hits were confirmed in rat and human CCAs (TCGA). Activation of interleukin-6 (IL6) and epidermal growth factor receptor (EGFR) pathways, and key genes in cancer-related glucose metabolic reprogramming, were validated in TAA-CCAs. In TAA-CCAs, G9a, an epigenetic pro-tumorigenic writer, was also increased. We show that EGFR signaling and mutant KRASG12D can both activate IL6 production in CCA cells. Furthermore, phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating with G9a expression. In a G9a activity-dependent manner, KRASG12D promoted PHGDH expression, glucose flow towards serine synthesis, and increased CCA cell viability. KRASG12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression. Conclusions In CCA, we identified new pro-tumorigenic mechanisms: Activation of EGFR signaling or KRAS mutation drives IL6 expression in tumour cells; Glucose metabolism reprogramming in iCCA includes activation of the serine-glycine pathway; Mutant KRAS drives PHGDH expression in a G9a-dependent manner; PHGDH and G9a emerge as therapeutic targets in iCCA.

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A Transcriptomic Signature for Risk‐Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma

Cited by 16 publications

References 55 publications

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma

Upregulation of POC1A in lung adenocarcinoma promotes tumour progression and predicts poor prognosis

New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming

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