Down regulation of Cathepsin W is associated with poor prognosis in pancreatic cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 10 2023
04 10 2023
Historique:
received:
20
04
2023
accepted:
16
09
2023
medline:
2
11
2023
pubmed:
5
10
2023
entrez:
4
10
2023
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on identifying new biomarkers for its early diagnosis and the prediction of patient survival. Genome-wide RNA and microRNA sequencing, bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs), followed by validation in an additional cohort of PDAC patients has been undertaken. To identify DEGs, genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA). We used Kaplan-Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest (RF), Max Voting, Adaboost, Gradient boosting machines (GBM), and Extreme Gradient Boosting (XGB) techniques were used, and Gradient boosting machines (GBM) were selected with 100% accuracy for analysis. Moreover, protein-protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs, and a combination of these obtained from machine learning algorithms and survival analysis. The results of Machine learning identified 23 genes with negative regulation, five genes with positive regulation, seven microRNAs with negative regulation, and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of the disease. In addition, the survival analysis showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9, and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in the disease pathogenesis can be used to detect patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.
Identifiants
pubmed: 37794108
doi: 10.1038/s41598-023-42928-y
pii: 10.1038/s41598-023-42928-y
pmc: PMC10551021
doi:
Substances chimiques
Cathepsin W
EC 3.4.22.-
MicroRNAs
0
Biomarkers
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16678Informations de copyright
© 2023. Springer Nature Limited.
Références
J Cancer. 2017 Feb 25;8(4):646-656
pubmed: 28367244
Front Oncol. 2022 May 13;12:708272
pubmed: 35646664
Front Oncol. 2022 Feb 04;11:716831
pubmed: 35186706
Cancer Res. 2012 Jul 1;72(13):3424-36
pubmed: 22564525
J Neural Eng. 2021 Apr 27;18(4):
pubmed: 33780909
Cancers (Basel). 2021 Jan 16;13(2):
pubmed: 33467038
Biochem Genet. 2023 Oct;61(5):1645-1674
pubmed: 36781813
Front Genet. 2020 May 05;11:441
pubmed: 32431729
Tumour Biol. 2013 Dec;34(6):3279-92
pubmed: 23949878
J Cell Commun Signal. 2023 Jul 10;:
pubmed: 37428302
Medicine (Baltimore). 2020 Sep 11;99(37):e22092
pubmed: 32925750
Curr Pharm Des. 2023;29(10):748-765
pubmed: 36892023
Lancet. 2016 Jul 2;388(10039):73-85
pubmed: 26830752
Nat Rev Clin Oncol. 2020 Feb;17(2):108-123
pubmed: 31705130
Rep Biochem Mol Biol. 2022 Jul;11(2):336-343
pubmed: 36164638
BMC Genomics. 2019 Feb 15;20(1):137
pubmed: 30767760
Mol Cell. 2015 May 21;58(4):610-20
pubmed: 26000846
Dig Dis Sci. 2017 Oct;62(10):2719-2727
pubmed: 28836087
Int J Biol Sci. 2022 Feb 7;18(4):1724-1736
pubmed: 35280673
J Biomol Struct Dyn. 2016;34(4):689-704
pubmed: 25990537
Nature. 2015 Feb 26;518(7540):495-501
pubmed: 25719666
Int J Cancer. 2021 Apr 5;:
pubmed: 33818764
Sci Rep. 2021 Nov 11;11(1):22036
pubmed: 34764329
Tumour Biol. 2015 Aug;36(8):6391-9
pubmed: 25861020
Aging (Albany NY). 2020 Feb 19;12(4):3371-3387
pubmed: 32074080
Pancreatology. 2018 Jan;18(1):61-67
pubmed: 29170051
Comb Chem High Throughput Screen. 2022;25(2):211-228
pubmed: 33390101
Cancer Genet. 2013 Jun;206(6):217-21
pubmed: 23933230
Sci Rep. 2023 Apr 15;13(1):6147
pubmed: 37061507
PLoS One. 2017 Feb 9;12(2):e0171759
pubmed: 28182647
BMC Pulm Med. 2021 Dec 20;21(1):420
pubmed: 34923982
Mol Pharm. 2018 Jan 2;15(1):63-71
pubmed: 29179557
Sensors (Basel). 2021 Sep 18;21(18):
pubmed: 34577467
J Hum Genet. 2017 Jan;62(1):33-40
pubmed: 27251005
World J Gastroenterol. 2021 Jul 21;27(27):4298-4321
pubmed: 34366606
Contemp Oncol (Pozn). 2015;19(1A):A68-77
pubmed: 25691825
Pancreatology. 2020 Sep;20(6):1195-1204
pubmed: 32800647
Biochem Genet. 2021 Oct;59(5):1326-1358
pubmed: 33813720
Cell Death Dis. 2017 Aug 3;8(8):e2971
pubmed: 28771225
Biochem Biophys Rep. 2020 Feb 09;22:100747
pubmed: 32072027
Neuron. 2021 Oct 20;109(20):3239-3251.e7
pubmed: 34478631
Neuron. 2021 Oct 20;109(20):3231-3233
pubmed: 34672980
Adv Biol Regul. 2015 Jan;57:1-9
pubmed: 25294678
NPJ Digit Med. 2018 Oct 2;1:52
pubmed: 31304331
Sci Rep. 2018 May 16;8(1):7638
pubmed: 29769534
Mol Cell Biochem. 2021 Dec;476(12):4191-4203
pubmed: 34324119
Cancer Treat Rev. 2021 May;96:102180
pubmed: 33812339
Int J Mol Med. 2016 Nov;38(5):1443-1449
pubmed: 27666346
Science. 2008 Sep 26;321(5897):1801-6
pubmed: 18772397