4.7 Article

Identification of Key mRNAs as Prediction Models for Early Metastasis of Pancreatic Cancer Based on LASSO

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2021.701039

Keywords

pancreatic cancer; metastasis; EMT; bioinformatics; precision medicine

Funding

  1. Basic Public Welfare Research Program of Zhejiang Province [LGF20H180004, GSE23952, 2020C03057]
  2. Zhejiang Province Key Research and Development Projects [GSE23952, 2020C03057]
  3. [GSE21654]
  4. [2021C03145]
  5. [BXPC-3-M8]

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By analyzing data from metastatic pancreatic cancer samples and cell lines, this study identified six genes associated with metastasis risk and constructed a risk-scoring model. The risk score based on the expression of these genes could better predict the risk of metastasis and serve as an important predictor for pancreatic cancer.
Pancreatic cancer is a highly malignant and metastatic tumor of the digestive system. Even after surgical removal of the tumor, most patients are still at risk of metastasis. Therefore, screening for metastatic biomarkers can identify precise therapeutic intervention targets. In this study, we analyzed 96 pancreatic cancer samples from The Cancer Genome Atlas (TCGA) without metastasis or with metastasis after R0 resection. We also retrieved data from metastatic pancreatic cancer cell lines from Gene Expression Omnibus (GEO), as well as collected sequencing data from our own cell lines, BxPC-3 and BxPC-3-M8. Finally, we analyzed the expression of metastasis-related genes in different datasets by the Limma and edgeR packages in R software, and enrichment analysis of differential gene expression was used to gain insight into the mechanism of pancreatic cancer metastasis. Our analysis identified six genes as risk factors for predicting metastatic status by LASSO regression, including zinc finger BED-Type Containing 2 (ZBED2), S100 calcium-binding protein A2 (S100A2), Jagged canonical Notch ligand 1 (JAG1), laminin subunit gamma 2 (LAMC2), transglutaminase 2 (TGM2), and the transcription factor hepatic leukemia factor (HLF). We used these six EMT-related genes to construct a risk-scoring model. The receiver operating characteristic (ROC) curve showed that the risk score could better predict the risk of metastasis. Univariate and multivariate Cox regression analyses revealed that the risk score was also an important predictor of pancreatic cancer. In conclusion, 6-mRNA expression is a potentially valuable method for predicting pancreatic cancer metastasis, assessing clinical outcomes, and facilitating future personalized treatment for patients with ductal adenocarcinoma of the pancreas (PDAC).

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