Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients

Aung, Tin May; Ciin, Mang Ngaih; Silsirivanit, Atit; Jusakul, Apinya; Lert-itthiporn, Worachart; Proungvitaya, Tanakorn; Roytrakul, Sittiruk; Proungvitaya, Siriporn

doi:10.3389/fpubh.2022.836985

Cited by 4 publications

(4 citation statements)

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“…Moreover, ANGPTL4 can participate in tumor energy metabolism in different NSCLC cells and affect cell proliferation through this process [82]. High expression of ANGPTL4 predicts adverse clinical outcomes in tumors, such as renal clear cell carcinoma, cholangiocarcinoma, melanoma, bladder cancer, and oral cancer [83][84][85][86][87]. In this study, ANGPTL4 was a high-risk gene that increased with tumor progression, suggesting a reduced survival rate and poor prognosis in LUAD patients.…”

Section: Discussionmentioning

confidence: 57%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 57%

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

et al. 2022

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“…cervical (14), colorectal (15), gastric (16), and breast (36) cancer. We previously reported overexpression of ANGPTL4 in CCA tissues and serum from patients, suggesting that it may be a marker for poor prognosis of CCA (17). San et al demonstrated that knockdown of ANGPTL4 reduced the death of CCA cells (18).…”

Section: Figure 4 Correlation Of Gene-expression Levels Between Angio...mentioning

confidence: 94%

“…In-solution tryptic digestion. Five micrograms of total protein isolated from cell lysates of ANGPTL4-silenced and scrambletreated control cells were digested according to the method developed by the Functional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Thailand (17). Briefly, samples were completely dissolved in 10 mM ammonium bicarbonate then 5 mM dithiothreitol in 10 mM ammonium bicarbonate was used to reduce disulfide bonds at 60˚C for 1 h and 15 mM iodoacetamide in 10 mM ammonium bicarbonate was used for alkylation of sulfhydryl groups at room temperature for 45 min in the dark.…”

Section: Methodsmentioning

confidence: 99%

“…ANGPTL4 expression is higher in several cancer types, such as esophageal squamous cell carcinoma (13), cervical cancer (14), colorectal cancer (15) and gastric cancer (16). Recently, we found higher ANGPTL4 expression in the sera and cancer tissues of patients with CCA, particularly, those with lymph node metastasis and advanced tumor stage (17). Related to this, San et al showed that ANGPTL4 was markedly up-regulated in anchorageindependently cultured CCA cells, and its knockdown tended to sensitize these cells to cell death and chemotherapy (18).…”

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Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells

Aung

Silsirivanit

Jusakul

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional signaling protein implicated in carbohydrate metabolism, inflammation, cancer growth and progression, anoikis resistance, angiogenesis, and metastasis. However, signaling pathways of ANGPTL4 in cholangiocarcinoma (CCA) remain unknown. The aim of this study was to explore ANGPTL4-related signaling proteins and pathways associated with CCA biology. Materials and Methods: ANGPTL4 of CCA cells was silenced by small interfering RNA (siRNA) with scramble control and ANGPTL4-related signaling proteins were investigated using mass spectrometry, bioinformatics tools and molecular docking. Results: Among the 321 differentially expressed proteins, 151 were downregulated. Among them, bioinformatic analyses revealed that ANGPTL4 interacts with DNA-dependent protein kinase catalytic subunit (PRKDC) and 60S ribosomal protein L21 (RPL21) via AKT serine/threonine kinase 1 (AKT1), mechanistic target of rapamycin kinase (MTOR) and ribosomal protein L5 (RPL5). Online database analysis showed that mRNA and protein expression levels of ANGPTL4-related signaling proteins were significantly higher in CCA than in normal tissues. Moreover, a high mRNA expression level was associated with high tumor grade (p<0.0001) and lymph node metastasis (p<0.0001). Conclusion: The signaling pathway of ANGPTL4 in CCA progression might be regulated by PRKDC and RPL21. Furthermore, high expression of ANGPTL4-related signaling proteins has potential to be used in clinical prognosis.Cholangiocarcinoma (CCA) is a type of highly aggressive cancer that can develop anywhere in the biliary tree or within the liver parenchyma (1). It is a rare cancer worldwide, but it is highly prevalent in Thailand, with the highest prevalence of 85/100,000 population being recorded in northeast Thailand and in association with the high prevalence of infection with the oncogenic liver fluke (Opisthorchis viverrini) (2-4). Although complete surgical resection is the only curative treatment for CCA, the postoperative 5-year survival rate of patients remains low (11.2%) due to late presentation of clinical symptoms (5, 6). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are currently used tumor markers for clinical diagnosis/prognosis of CCA. However, elevation of these markers has also been found in benign biliary diseases, pancreatic cancer, and colorectal cancer, amongst others (7-9). Hence, developing reliable biomarkers and exploring the mechanisms underlying CCA progression are essential to improve the outcomes of patients with CCA.Angiopoietin-like protein 4 (ANGPTL4) is a secreted protein with a highly hydrophobic signal peptide and has an N-terminal coiled-coil domain and a C-terminal fibrinogen-like fragment (10). It has a variety of biological roles in both normal and 490

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An auxiliary diagnostic approach based on traditional Chinese medicine constitutions for older patients with frailty

Gu,

Wang,

Yang

et al. 2024

Clinical and Translational Dis

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IntroductionAs global population ages, frailty has surfaced as a major public health challenge. Given the heterogeneity of frailty in the clinical presentation, it is imperative to develop personalised diagnostic and treatment strategies. The traditional Chinese medicine (TCM) constitution offers notable advantages in discerning individual differences. This study aims to elucidate the association between TCM constitutions and frailty, providing insights into the application of TCM for the frailty management.MethodsAn observational study was conducted at Huadong hospital from July 2022 to November 2023. A total of 241 older patients were recruited. Each patient underwent assessments for the TCM constitution and frailty status. Comprehensive data collection encompassed medical history, biochemical indicators, bone mineral density (BMD), body composition and physical performance metrics. Plasma samples were also collected to detect levels of inflammatory factors and lymphogenesis‐related factors, including IL‐1β, TNF‐α, VEGF‐C, ANGPTL4 and ACV‐A. Multi‐level statistical analysis was used to establish the relationship of TCM constitutions with frailty.ResultsAmongst all participants, 54 individuals were classified as non‐frail, 90 individuals as pre‐frail and 97 individuals as frail. Regression analysis indicated that frailty was closely associated with four imbalanced TCM constitutions: Qi deficiency, phlegm dampness, blood stasis and Qi depression. Subsequent analysis demonstrated that Qi deficiency was associated with decreased BMD, phlegm dampness with elevated high‐density lipoprotein levels, Blood stasis with elevated blood glucose levels, and Qi depression with both decreased BMD and elevated low‐density lipoprotein levels. Furthermore, individuals characterised by imbalanced TCM constitutions exhibited inferior handgrip strength, walking pace, lower limb strength and higher levels of inflammatory factors and lymphogenesis‐related factors compared to those with balanced TCM constitution.ConclusionFrailty is independently associated with Qi deficiency, phlegm dampness, blood stasis and Qi depression. Personalised diagnostic approaches based on the TCM constitution may offer valuable insights for directing treatment for older patients with frailty.

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Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients

Cited by 4 publications

References 43 publications

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

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

Prediction of Angiopoietin-like Protein 4-related Signaling Pathways in Cholangiocarcinoma Cells

An auxiliary diagnostic approach based on traditional Chinese medicine constitutions for older patients with frailty

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