The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09577-2 |
| _version_ | 1817982338487812096 |
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| author | Hong Luan Ye He Tuo Zhang Yanna Su Liping Zhou |
| author_facet | Hong Luan Ye He Tuo Zhang Yanna Su Liping Zhou |
| author_sort | Hong Luan |
| collection | DOAJ |
| description | Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown. Methods We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein–protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER). Results In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes. Conclusions Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes. |
| first_indexed | 2024-04-13T23:18:31Z |
| format | Article |
| id | doaj.art-7d3f94e10cce4370999a29d24aff3413 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T23:18:31Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7d3f94e10cce4370999a29d24aff34132022-12-22T02:25:18ZengBMCBMC Cancer1471-24072022-04-0122111410.1186/s12885-022-09577-2The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinomaHong Luan0Ye He1Tuo Zhang2Yanna Su3Liping Zhou4Department of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityDepartment of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityDepartment of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityDepartment of Laboratory Medicine, The First Affiliated Hospital of China Medical UniversityDepartment of Post Graduation Training, The First Affiliated Hospital of China Medical UniversityAbstract Background Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown. Methods We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein–protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER). Results In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes. Conclusions Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes.https://doi.org/10.1186/s12885-022-09577-2Liver metastasisBiomarkerPancreatic ductal adenocarcinomaBioinformatics analysisSPARCTPM1 |
| spellingShingle | Hong Luan Ye He Tuo Zhang Yanna Su Liping Zhou The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma BMC Cancer Liver metastasis Biomarker Pancreatic ductal adenocarcinoma Bioinformatics analysis SPARC TPM1 |
| title | The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma |
| title_full | The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma |
| title_fullStr | The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma |
| title_short | The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma |
| title_sort | identification of liver metastasis and prognosis associated genes in pancreatic ductal adenocarcinoma |
| topic | Liver metastasis Biomarker Pancreatic ductal adenocarcinoma Bioinformatics analysis SPARC TPM1 |
| url | https://doi.org/10.1186/s12885-022-09577-2 |
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