Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma

Suda, Tsuyoshi; Yamashita, Taro; Sunagozaka, Hajime; Okada, Hikari; Nio, Kouki; Sakai, Yoshio; Mizukoshi, Eishiro; Honda, Masao

doi:10.3390/ijms23052801

Cited by 19 publications

(13 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a member of a typical carcinogenic signaling pathway, DKK1 plays an important anticancer role in human cancers [ 51 , 52 ]. Evidence has shown that DKK1 is not only involved in osteogenesis but also plays a central role in promoting tumor bone metastasis [ 53 , 54 ]. In the tumor tissue of thyroid papillary carcinoma (PTC), abnormal nuclear localization of β-catenin is associated with poor prognosis of PTC patients and thus contributes to tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Guidelines on lung adenocarcinoma prognosis based on immuno-glycolysis-related genes

et al. 2022

View full text Add to dashboard Cite

Objectives This study developed a new model for risk assessment of immuno-glycolysis-related genes for lung adenocarcinoma (LUAD) patients to predict prognosis and immunotherapy efficacy. Methods LUAD samples and data obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases are used as training and test columns, respectively. Twenty-two (22) immuno-glycolysis-related genes were screened, the patients diagnosed with LUAD were divided into two molecular subtypes by consensus clustering of these genes. The initial prognosis model was developed using the multiple regression analysis method and Receiver Operating characteristic (ROC) analysis was used to verify its predictive potential. Gene set enrichment analysis (GSEA) showed the immune activities and pathways in different risk populations, we calculated immune checkpoints, immune escape, immune phenomena (IPS), and tumor mutation burden (TMB) based on TCGA datasets. Finally, the relationship between the model and drug sensitivity was analyzed. Results Fifteen (15) key differentially expressed genes (DEGs) with prognostic value were screened and a new prognostic model was constructed. Four hundred and forty-three (443) samples were grouped into two different risk cohorts based on median model risk values. It was observed that survival rates in high-risk groups were significantly low. ROC curves were used to evaluate the model’s accuracy in determining the survival time and clinical outcome of LUAD patients. Cox analysis of various clinical factors proved that the risk score has great potential as an independent prognostic factor. The results of immunological analysis can reveal the immune infiltration and the activity of related functions in different pathways in the two risk groups, and immunotherapy was more effective in low-risk patients. Most chemotherapeutic agents are more sensitive to low-risk patients, making them more likely to benefit. Conclusion A novel prognostic model for LUAD patients was established based on IGRG, which could more accurately predict the prognosis and an effective immunotherapy approach for patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Guidelines on lung adenocarcinoma prognosis based on immuno-glycolysis-related genes

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The most frequent mutations in HCC involve CTNNB1 (15.9–30%), AXIN1 (4.5–8%), and APC (0.8–3%) [ 263 , 283 , 340 ]. DKK1 is considered as an early-stage HCC biomarker [ 341 , 342 ], and CTNNB1 is enriched in proteomic subclass 3 [ 64 ]. CTNNB1 mutations are significantly associated with telomerase reverse-transcriptase promoter (TERT) mutations [ 343 ].…”

Section: Review Of Established and Novel Potential Targets In Hccmentioning

confidence: 99%

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets

Pessino,

Scotti,

Maggi

2024

Cancers

View full text Add to dashboard Cite

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint inhibitors, such as atezolizumab and pembrolizumab, show efficacy, and combination therapies enhance clinical responses. Despite this, the treatment of hepatocellular carcinoma (HCC) remains a challenge, as the complex tumor ecosystem and the immunosuppressive microenvironment associated with it hamper the efficacy of the available therapeutic approaches. This review explores current and advanced approaches to treat HCC, considering both known and new potential targets, especially derived from proteomic analysis, which is today considered as the most promising approach. Exploring novel strategies, this review discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), and engineered antibodies. It then reports a systematic analysis of the main ligand/receptor pairs and molecular pathways reported to be overexpressed in tumor cells, highlighting their potential and limitations. Finally, it discusses TGFβ, one of the most promising targets of the HCC microenvironment.

show abstract

“…Additionally, activation of the Wnt signaling pathway reportedly controls the stemness of CSCs in different types of cancers including hepatocellular carcinoma (HCC), and colon, lung, and other cancers. [144][145][146][147][148] According to clinical practice, targeted treatment using MEKi (selumetinib, trametinib, and PD318088) inadvertently increased Wnt activity and led to enhanced stemness and tumor relapse in colorectal cancer. 149 Similarly, valproic acid, which was originally regarded as a histone deacetylase (HDAC) inhibitor in breast cancer treatment, can activate Wnt signaling pathway and promote the pool of mammary CSCs, leading to tumor progression.…”

Section: Epigenetic Mechanismsmentioning

confidence: 99%

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Pang

Yang

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity. Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employ combination treatments. In this review, we delineate the formation of tumor cell plasticity and its manipulation of tumor evasion from targeted therapy. We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types of tumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance. New therapeutic strategies such as inhibition or reversal of tumor cell plasticity are also presented. We also discuss the multitude of clinical trials that are ongoing worldwide with the intention of improving clinical outcomes. These advances provide a direction for developing novel therapeutic strategies and combination therapy regimens that target tumor cell plasticity.

show abstract

Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma

Cited by 19 publications

References 51 publications

Guidelines on lung adenocarcinoma prognosis based on immuno-glycolysis-related genes

Guidelines on lung adenocarcinoma prognosis based on immuno-glycolysis-related genes

Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets

Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies

Contact Info

Product

Resources

About