Enhanced expression of FGF19 predicts poor prognosis in patients with non-small cell lung cancer

Chen, Jia; Shao, Jingjing; Shen, Aiguo; Zhu, Xinghua; Zhang, Xunlei; Sun, Hui; Wei, Sheng; Yang, Lifen

doi:10.21037/jtd-21-126

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…FGF19 can promote the occurrence of colorectal cancer by regulating metabolic biological functions, such as bile acid biosynthesis and insulin resistance ( Peng et al, 2020 ). The expression of FGF19 is significantly up-regulated in non-small cell lung cancer, and is associated with poor prognosis ( Chen et al, 2021a ). FGF19 stimulates cell proliferation and invasion by activating AKT-MAPK signaling pathway ( Hu & Cong, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer

Zhu

Huang

Thakur

et al. 2023

PeerJ

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Background Chemotherapy is one of the primary treatments for ovarian cancer patients. Autophagy has been linked to chemotherapy resistance in tumor cells. Recent studies have suggested that fibroblast growth factor 19 (FGF19) may be involved in the onset and progression of malignancies. However, the relationship between FGF19 and autophagy in ovarian cancer is still unknown. Methods Next-generation sequencing (NGS) was conducted to analyze gene mutation profiles of 62 cases of high grade serous ovarian cancer (HGSOC). Fluorescence in situ hybridization (FISH) was performed to validate the amplification of FGF19 in HGSOC tissues. Quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to analyze the difference of FGF19 in mRNA and protein expression. Meanwhile, bioinformatics techniques were used to analyze the expression profiles of FGF19 and the correlation with prognosis. Besides, immunofluorescence, transmission electron microscopy and Cell Counting Kit 8 (CCK-8) were used to investigate the potential mechanisms. Results In this study, we found that FGF19 promotes cisplatin resistance in ovarian cancer cells by inducing autophagy. NGS analysis of 62 HGSOC cases identified a significantly amplified gene, FGF19. In addition, the expression level of FGF19 in ovarian cancer samples was higher than that in normal samples. FISH results showed a positive correlation between amplification and expression of FGF19. Knockdown of FGF19 inhibited the cell autophagy through decrease in the expression of LC3 and Beclin 1, and increase in the expression of SQSTM1/p62. Furthermore, we observed that p38 MAPK phosphorylation was down-regulated after FGF19 knockdown. IFN-γ, a potential p38 MAPK activator, counteracted the inhibition of cell autophagy and the anti-proliferation effect of cisplatin induced by FGF19 knockdown in ovarian cancer cells. Conclusion FGF19 increases autophagy and chemoresistance in ovarian cancer by activating the p38 MAPK pathway. These results could point to FGF19 being a potential therapeutic target for ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer

Zhu

Huang

Thakur

et al. 2023

PeerJ

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“…S1 ). In order to classify samples into high or low expression groups, we used the cut-off levels of 50% for nuclear and cytoplasmic VDR expression, 28 and 10% for nuclear p21 expression. For cytoplasmic p21, CYP27B1, CYP24A1, and E-cadherin, a score of 0–1 was categorized as negative, and a score of 2–3 was considered as positive ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

Vitamin D Receptor Expression and its Clinical Significance in Papillary Thyroid Cancer

Kim

Koo

et al. 2022

Technol Cancer Res Treat

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Objective: This study aimed to evaluate the association between vitamin D receptor (an essential component in the vitamin D signaling pathway) and serum vitamin D as well as its clinical significance in papillary thyroid cancer. Methods: This prospective cohort study comprised patients with thyroid tumors who visited our hospital, from 2017 to 2018. The level of vitamin D receptor expression from thyroid tissue was measured in patients with thyroid tumor and evaluated for correlation with serum vitamin D levels and clinicopathologic characteristics of papillary thyroid cancer. Data from 501 patients with papillary thyroid cancer from The Cancer Genome Atlas database were analyzed. Results: Increased vitamin D receptor protein and mRNA expression were observed in papillary thyroid cancer compared to those in normal and benign tissues. Lower vitamin D receptor protein expression was associated with high TNM stage papillary thyroid cancer and low p21 protein expression. Lower relative vitamin D receptor mRNA expression in papillary thyroid cancer was associated with low serum 25-hydroxyvitamin D level. The Cancer Genome Atlas database showed a positive correlation among mRNA expression of vitamin D receptor, CYP24A1, and p21. Conclusions: An association between decreased vitamin D receptor protein expression and advanced stage papillary thyroid cancer, and a correlation between low vitamin D receptor mRNA expression with low serum 25-hydroxyvitamin D level was observed. Low vitamin D receptor expression in papillary thyroid cancer was shown to positively correlate with low serum vitamin D level and disease aggressiveness.

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“…A previous study suggested that the occurrence and development of lung cancer are associated with the dysregulated expression and mutation of oncogenes and tumor suppressor genes ( 8 ), and a number of proteins and non-coding RNAs have been demonstrated to be involved in the pathogenesis of the disease ( 9 , 10 ). Previous studies have demonstrated that Musashi 2 and fibroblast growth factor 19 act as independent prognostic biomarkers in non-small cell lung cancer (NSCLC) ( 11 , 12 ). Mitotic spindle organizing protein 2A overexpression promotes NSCLC cell proliferation and invasion, which is associated with poor NSCLC prognosis ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Calponin 3 suppresses proliferation, migration and invasion of non‑small cell lung cancer cells

2021

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Calponin 3 (CNN3) is known to serve a role in certain types of cancer, such as gastric cancer and colorectal cancer. The present study investigated the clinical significance of CNN3 in non-small cell lung cancer (NSCLC) by evaluating its expression profile and relationship with disease prognosis using the Gene Expression Omnibus repository, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier plotter analysis. CNN3 mRNA expression was measured using reverse transcription-quantitative PCR, while the protein expression level was measured using western blot analysis. Cell proliferation, cell cycle and apoptosis, and migration and invasion were analyzed using MTS assay, flow cytometry and Transwell assays, respectively. These results revealed that CNN3 mRNA expression was downregulated in NSCLC tissues compared with that in normal tissues. Additionally, CNN3 expression had a high diagnostic value based on the GSE2514 dataset and the data from The Cancer Genome Atlas and the Genotype Tissue Expression database, whereas it had a low diagnostic value based on the GSE10072 dataset. Furthermore, CNN3 expression was associated with survival in patients with lung adenocarcinoma (LUAD), whereas it was not associated with survival in patients with lung squamous cell carcinoma (LUSC) according to the Kaplan-Meier plotter results. According to the data from GEPIA2, and the GSE72094, GSE41271 and GSE31210 datasets, CNN3 expression was not associated with the prognosis of patients with LUAD and LUSC. The mRNA and protein expression levels of CNN3 were lower in two NSCLC cell lines (A549 and SK-MES-1) than in a human bronchial epithelial cell line (BEAS-2B). CNN3 overexpression suppressed cell proliferation, migration and invasion, induced G 1 -phase arrest, promoted apoptosis and suppressed PI3K/AKT signaling pathway activation in the NSCLC cell lines, whereas CNN3 overexpression had no effect on cell morphology. In conclusion, CNN3 suppressed the proliferation and metastasis of NSCLC cells by downregulating the PI3K/AKT signaling pathway, making it a potential therapeutic target in this disease.

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Enhanced expression of FGF19 predicts poor prognosis in patients with non-small cell lung cancer

Cited by 4 publications

References 30 publications

FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer

FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer

Vitamin D Receptor Expression and its Clinical Significance in Papillary Thyroid Cancer

Calponin 3 suppresses proliferation, migration and invasion of non‑small cell lung cancer cells

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