Identification of Key MRNAs As Prediction Models for Early Metastasis of Pancreatic Cancer Based on LASSO

Overview

Journal Front Bioeng Biotechnol

Date 2021 Sep 6

PMID 34485257

Citations 6

Authors

Ke Xue

Huilin Zheng

Xiaowen Qian

Zheng Chen

Yangjun Gu

Zhenhua Hu

Lei Zhang

Jian Wan

Affiliations

Soon will be listed here.

Abstract

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 . 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).

Citing Articles

Pan-cancer bioinformatics analysis of hepatic leukemia factor and further validation in colorectal cancer.

Lin Y, Xiong Z, Yang Y, Li W, Huang W, Lin M Transl Cancer Res. 2024; 13(7):3299-3317.

PMID: 39145052 PMC: 11319992. DOI: 10.21037/tcr-23-2274.

Gao X, Yang C, Li H, Shao L, Wang M, Su R Sci Rep. 2023; 13(1):20380.

PMID: 37990105 PMC: 10663558. DOI: 10.1038/s41598-023-47886-z.

Multimodal AI for prediction of distant metastasis in carcinoma patients.

Olatunji I, Cui F Front Bioinform. 2023; 3():1131021.

PMID: 37228671 PMC: 10203594. DOI: 10.3389/fbinf.2023.1131021.

An epithelial-mesenchymal transition-related mRNA signature associated with the prognosis, immune infiltration and therapeutic response of colon adenocarcinoma.

Zhang Y, Li Y, Zuo Z, Li T, An Y, Zhang W Pathol Oncol Res. 2023; 29:1611016.

PMID: 36910014 PMC: 9998511. DOI: 10.3389/pore.2023.1611016.

Identifying cancer cell-secreted proteins that activate cancer-associated fibroblasts as prognostic factors for patients with pancreatic cancer.

Luo Q, Liu J, Fu Q, Zhang X, Yu P, Liu P J Cell Mol Med. 2022; 26(22):5657-5669.

PMID: 36282889 PMC: 9667520. DOI: 10.1111/jcmm.17596.

References

Macias N, Sayagues J, Esteban C, Iglesias M, Gonzalez L, Quinones-Sampedro J . Histologic Tumor Grade and Preoperative Bilary Drainage are the Unique Independent Prognostic Factors of Survival in Pancreatic Ductal Adenocarcinoma Patients After Pancreaticoduodenectomy. J Clin Gastroenterol. 2017; 52(2):e11-e17. DOI: 10.1097/MCG.0000000000000793. View

McDonald O, Li X, Saunders T, Tryggvadottir R, Mentch S, Warmoes M . Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat Genet. 2017; 49(3):367-376. PMC: 5695682. DOI: 10.1038/ng.3753. View

Palena C, Fernando R, Hamilton D . An immunotherapeutic intervention against tumor progression: Targeting a driver of the epithelial-to-mesenchymal transition. Oncoimmunology. 2014; 3(1):e27220. PMC: 3929358. DOI: 10.4161/onci.27220. View

Stratford J, Bentrem D, Anderson J, Fan C, Volmar K, Marron J . A six-gene signature predicts survival of patients with localized pancreatic ductal adenocarcinoma. PLoS Med. 2010; 7(7):e1000307. PMC: 2903589. DOI: 10.1371/journal.pmed.1000307. View

Chen Y, Gao S, Chen J, Wang G, Wang Z, Zhou B . Serum CA242, CA199, CA125, CEA, and TSGF are Biomarkers for the Efficacy and Prognosis of Cryoablation in Pancreatic Cancer Patients. Cell Biochem Biophys. 2014; 71(3):1287-91. DOI: 10.1007/s12013-014-0345-2. View

Elinav E, Nowarski R, Thaiss C, Hu B, Jin C, Flavell R . Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013; 13(11):759-71. DOI: 10.1038/nrc3611. View

Zemmour C, Bertucci F, Finetti P, Chetrit B, Birnbaum D, Filleron T . Prediction of early breast cancer metastasis from DNA microarray data using high-dimensional cox regression models. Cancer Inform. 2015; 14(Suppl 2):129-38. PMC: 4426954. DOI: 10.4137/CIN.S17284. View

Tibshirani R . The lasso method for variable selection in the Cox model. Stat Med. 1997; 16(4):385-95. DOI: 10.1002/(sici)1097-0258(19970228)16:4<385::aid-sim380>3.0.co;2-3. View

Ohuchida K, Mizumoto K, Miyasaka Y, Yu J, Cui L, Yamaguchi H . Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis. J Pathol. 2007; 213(3):275-82. DOI: 10.1002/path.2250. View

10.

Chen S, Wang Y, Ni C, Meng G, Sheng X . HLF/miR-132/TTK axis regulates cell proliferation, metastasis and radiosensitivity of glioma cells. Biomed Pharmacother. 2016; 83:898-904. DOI: 10.1016/j.biopha.2016.08.004. View

11.

Birnbaum D, Finetti P, Lopresti A, Gilabert M, Poizat F, Raoul J . A 25-gene classifier predicts overall survival in resectable pancreatic cancer. BMC Med. 2017; 15(1):170. PMC: 5606023. DOI: 10.1186/s12916-017-0936-z. View

12.

Otsuki Y, Saya H, Arima Y . Prospects for new lung cancer treatments that target EMT signaling. Dev Dyn. 2017; 247(3):462-472. DOI: 10.1002/dvdy.24596. View

13.

Chen D, Davis-Yadley A, Huang P, Husain K, Centeno B, Permuth-Wey J . Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma. PLoS One. 2015; 10(8):e0133562. PMC: 4527782. DOI: 10.1371/journal.pone.0133562. View

14.

Zheng X, Carstens J, Kim J, Scheible M, Kaye J, Sugimoto H . Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015; 527(7579):525-530. PMC: 4849281. DOI: 10.1038/nature16064. View

15.

Feng Z, Li K, Lou J, Wu Y, Peng C . An EMT-Related Gene Signature for Predicting Response to Adjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma. Front Cell Dev Biol. 2021; 9:665161. PMC: 8119901. DOI: 10.3389/fcell.2021.665161. View

16.

Li C, Zeng X, Yu H, Gu Y, Zhang W . Identification of hub genes with diagnostic values in pancreatic cancer by bioinformatics analyses and supervised learning methods. World J Surg Oncol. 2018; 16(1):223. PMC: 6237021. DOI: 10.1186/s12957-018-1519-y. View

17.

Jiang W, Bai W, Li J, Liu J, Zhao K, Ren L . Leukemia inhibitory factor is a novel biomarker to predict lymph node and distant metastasis in pancreatic cancer. Int J Cancer. 2020; 148(4):1006-1013. DOI: 10.1002/ijc.33291. View

18.

Barry S, Chelala C, Lines K, Sunamura M, Wang A, Marelli-Berg F . S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells. Clin Exp Metastasis. 2012; 30(3):251-64. DOI: 10.1007/s10585-012-9532-y. View

19.

Luttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Kloppel G . The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000; 191(2):154-61. DOI: 10.1002/(SICI)1096-9896(200006)191:2<154::AID-PATH603>3.0.CO;2-C. View

20.

Lee J, Lee J, Kim J . Association of Jagged1 expression with malignancy and prognosis in human pancreatic cancer. Cell Oncol (Dordr). 2020; 43(5):821-834. DOI: 10.1007/s13402-020-00527-3. View