Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Liu, Xiaolong; Ma, Bin; Chen, Mali; Zhang, Yaqing; Ma, Zhen; Chen, Hao

doi:10.3389/fgene.2021.720849

Cited by 6 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy is a process by which cellular material is delivered to lysosomes or vacuoles for degradation and recycling ( Chen et al, 2021b ). Cell autophagy has important regulatory roles on the cancer pathogenesis and therapeutic response ( Liu et al, 2021b ). For instance, Fusobacterium nucleatum has been found to confer chemoresistance in oesophageal squamous cell carcinoma cells by inducing autophagy ( Liu et al, 2021a ).…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

Huang

Thakur

et al. 2023

PeerJ

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Zhu

Huang

Thakur

et al. 2023

PeerJ

View full text Add to dashboard Cite

show abstract

“…BRCA is the predominant malignancy affecting women globally and exhibits the highest fatality rate in female patients. ATGs exert a dual influence on BRCA, as shown in previous studies where certain ATGs have been implicated in inhibiting tumorigenesis, whereas others have been found to promote tumor characteristics in malignant mammary cells (35)(36)(37)(38). Considering the important role of autophagy in BRCA, an autophagy-related prognosis model of BRCA in TCGA dataset was constructed, and it was found that NRG2 served as a hub gene through the PPI network of DEATGs.…”

Section: Discussionmentioning

confidence: 93%

Prognostic biomarker NRG2 correlates with autophagy and epithelial‑mesenchymal transition in breast cancer

Zhou,

Dai,

Zhou

et al. 2024

Oncol Lett

View full text Add to dashboard Cite

Breast cancer (BRCA) is a leading cause of death in women worldwide, accounting for 31% of female cancer. Autophagy plays a crucial role in cancer progression, however, the function of autophagy-related gene neuroregulatory protein 2 (NRG2) in BRCA and its underlying molecular mechanisms remain unclear. In the present study, the expression of the NRG2 gene in BRCA was significantly down-regulated compared with the normal controls. The low expression level of NRG2 was related to poor survival rate of BRCA. The receiver operating characteristic curve of NRG2 showed a good diagnostic value for distinguishing BRCA from normal tissues (AUC=0.932). GO-KEGG analysis and GSEA enrichment analysis showed that NRG2 and its regulated genes were enriched in autophagy-related and immune-related pathways, and NRG2 was positively correlated with a number of immune cells and immune checkpoint genes. In addition, knockdown of NRG2 significantly promoted the proliferation, invasion and migration of BRCA cells. The autophagy marker, LC3-II and epithelial-mesenchymal transition (EMT) marker, vimentin were increased, while P62 and E-cadherin were decreased in response to NRG2 depletion. The findings of the present study demonstrated that NRG2 acts as a tumor suppressor factor that contributes to the immune escape and anti-tumor immunity inhibition by regulating the pathological process of autophagy and EMT, suggesting that NRG2 could be used as a prognostic biomarker and clinical target for BRCA therapy.

show abstract

“…Several studies suggest the vital role of autophagy in cancers, including gastric cancer. A differential expression analysis of autophagy-related genes (ARGs) in gastric cancer was carried out by Li and collaborators [ 31 ], who report a total of seven prognosis-related ARGs, including DLC1, as independent prognostic markers for gastric cancer [ 31 ]. A biomarker-based retrospective study [ 32 ] provides support for the use of the lymphocyte-to-monocyte ratio (LMR) as a novel predictor for colorectal liver cancer (CLC) treated with radiofrequency ablation (RFA).…”

Section: Discussionmentioning

confidence: 99%

DLC1 as Druggable Target for Specific Subsets of Gastric Cancer: An RNA-seq-Based Study

et al. 2023

View full text Add to dashboard Cite

Background: Gastric cancer has been ranked the third leading cause of cancer death worldwide. Its detection at the early stage is difficult because patients mostly experience vague and non-specific symptoms in the early stages. Methods: The RNA-seq datasets of both gastric cancer and normal samples were considered and processed. The obtained differentially expressed genes were then subjected to functional enrichment analysis and pathway analysis. An implicit atomistic molecular dynamics simulation was executed on the selected protein receptor for 50 ns. The electrostatics, surface potential, radius of gyration, and macromolecular energy frustration landscape were computed. Results: We obtained a large number of DEGs; most of them were down-regulated, while few were up-regulated. A DAVID analysis showed that most of the genes were prominent in the KEGG and Reactome pathways. The most prominent GAD disease classes were cancer, metabolic, chemdependency, and infection. After an implicit atomistic molecular dynamics simulation, we observed that DLC1 is electrostatically optimized, stable, and has a reliable energy frustration landscape, with only a few maximum energy frustrations in the loop regions. It has a good functional and binding affinity mechanism. Conclusions: Our study revealed that DLC1 could be used as a potential druggable target for specific subsets of gastric cancer.

show abstract

Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy

Cited by 6 publications

References 47 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

Prognostic biomarker NRG2 correlates with autophagy and epithelial‑mesenchymal transition in breast cancer

DLC1 as Druggable Target for Specific Subsets of Gastric Cancer: An RNA-seq-Based Study

Contact Info

Product

Resources

About