Published online May 7, 2019. doi: 10.3748/wjg.v25.i17.2086
Peer-review started: January 10, 2019
First decision: February 26, 2019
Revised: March 20, 2019
Accepted: April 10, 2019
Article in press: April 10, 2019
Published online: May 7, 2019
Pancreatic cancer is a malignant tumor with a poor prognosis that has almost equal mortality and morbidity in patients. At present, more and more studies have found that autophagy is closely related to the occurrence, development, differentiation and prognosis of pancreatic cancer. Autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3), as a key protein in the autophagy process, is involved in the formation of the autophagosome. A study by our research group found that high expression of LC3 in pancreatic cancer was positively correlated with neural invasion and poor prognosis. With the development of genomics, gene expression microarray technology, proteomics and bioinformatics, the ability to manipulate and characterize human genes and their products has been acquired. Disease-related genes have been studied at the molecular level to understand the pathogenesis of diseases. On the basis of previous studies and using LC3 as a guidance index, the autophagy gene expression profile of pancreatic cancer was analyzed to guide the functional annotation of differentially expressed genes and to enhance the reliability of bioinformatics prediction and analysis. Thus, to provide a basis for the study of the molecular mechanism of autophagy in pancreatic cancer.
This study focused on the differentially expressed genes based on LC3 to analyze the gene expression profile of autophagy in pancreatic cancer. Thus, to provide a basis for the study of the molecular mechanism of autophagy in pancreatic cancer.
To identify differentially expressed genes in autophagy of pancreatic cancer and to provide a basis for exploring the molecular mechanism of autophagy of pancreatic cancer cells and finding new targets for diagnosis and treatment of pancreatic cancer.
On the basis of previous studies and using LC3 as a guidance index, differentially expressed genes involved in the autophagy of pancreatic cancer were identified by a gene expression microarray technique. Protein interaction networks were constructed and the functional clustering of differentially expressed genes was carried out. Key interacting proteins or genes between modules were screened and evaluated by statistical methods, and the pathogenesis of pancreatic cancer was explored.
After removing genes that are clearly defined in the GENE database, 347 differentially expressed genes were obtained. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed a highly significant new pathway, hsa04216 (ferroptosis), a new cell death pattern associated with iron death. The ubiquitin C (UBC) as a pivot of module interactions, connected several modules related to cancer and autophagy and plays an important role in multiple cell death modules related to autophagy.
In this study, we identified differentially expressed genes based on the LC3 to analyze the gene expression profile of autophagy in pancreatic cancer. Three hundred and forty-seven genes that have no confirmed association with the autophagy process of human pancreatic cancer cells in previous studies were concentrated, and the key pathways involved in autophagy were enriched. Furthermore, a key gene UBC which is closely related to the occurrence of perineural invasion (PNI) was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through UBC.
With the development of genomics, gene expression microarray technology, proteomics and bioinformatics, we have been able to study disease-related genes at the molecular level to understand the pathogenesis of disease, thus to seek new research directions or to find new targets for clinical diagnosis and treatment. In this study, LC3 was used as a target to explore the differential genes related to autophagy in pancreatic cancer cells. Three hundred and forty-seven genes that have no confirmed association with the autophagy process of human pancreatic cancer cells in previous studies were concentrated, it is obviously unrealistic to analyze all the genes interacting with LC3 in vitro. Nevertheless, a key gene UBC which is closely related to the occurrence of PNI was determined. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. Suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through UBC. Therefore, we have planned to supplement some vitro and vivo experiments to further analysis the relationship between them and explore the molecular mechanism of phagocytosis in pancreatic cancer cells.