Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts.
Breast cancer
Differential expression
Pathway
Somatic mutation
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
21 Jun 2022
21 Jun 2022
Historique:
received:
11
02
2022
accepted:
15
06
2022
entrez:
21
6
2022
pubmed:
22
6
2022
medline:
24
6
2022
Statut:
epublish
Résumé
Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue. We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively. In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA. Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue.
METHODS
METHODS
We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively.
RESULTS
RESULTS
In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA.
CONCLUSION
CONCLUSIONS
Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.
Identifiants
pubmed: 35729536
doi: 10.1186/s12885-022-09779-8
pii: 10.1186/s12885-022-09779-8
pmc: PMC9210628
doi:
Substances chimiques
Adrenergic Agents
0
Biomarkers, Tumor
0
Cholinergic Agents
0
Glucocorticoids
0
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
680Subventions
Organisme : China Scholarship Council
ID : 201806240005
Organisme : Cancerfonden
ID : 20 0846 PjF
Organisme : National Natural Science Foundation of China
ID : 8187111500
Organisme : Vetenskapsrådet
ID : 2018-00648
Informations de copyright
© 2022. The Author(s).
Références
Cancer Epidemiol Biomarkers Prev. 2017 Dec;26(12):1781-1787
pubmed: 28939587
Mar Drugs. 2020 Apr 07;18(4):
pubmed: 32272701
Oncotarget. 2017 May 9;8(19):32101-32116
pubmed: 28404880
Int J Cancer. 2021 Jan 1;148(1):28-37
pubmed: 32621751
Bioinformatics. 2004 Jan 1;20(1):93-9
pubmed: 14693814
Clin Cancer Res. 2020 Jun 1;26(11):2565-2572
pubmed: 32019858
J Oncol. 2021 Feb 27;2021:6610511
pubmed: 33727922
Nature. 2019 Mar;567(7749):540-544
pubmed: 30867597
Sci Rep. 2016 Jan 27;6:19771
pubmed: 26813959
J Cancer Epidemiol. 2014;2014:469251
pubmed: 24955090
Sci Rep. 2019 May 17;9(1):7507
pubmed: 31101846
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Clin Cancer Res. 2016 Feb 1;22(3):765-772
pubmed: 26490316
Int Immunopharmacol. 2020 Jul;84:106514
pubmed: 32311671
J Clin Oncol. 2020 Jul 10;38(20):2310-2320
pubmed: 32442060
Cancer Res. 2011 Oct 15;71(20):6360-70
pubmed: 21868756
Sci Rep. 2017 Apr 04;7:45686
pubmed: 28374823
JAMA Oncol. 2016 Aug 1;2(8):1040-7
pubmed: 27100299
Breast Cancer Res Treat. 2016 Jul;158(1):43-50
pubmed: 27314577
Ann Transl Med. 2019 Nov;7(22):640
pubmed: 31930041
Ann Oncol. 2013 Sep;24(9):2206-23
pubmed: 23917950
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Genome Biol. 2010;11(3):R25
pubmed: 20196867
PLoS One. 2018 Dec 13;13(12):e0208982
pubmed: 30543688
Clin Cancer Res. 2018 Jul 15;24(14):3433-3446
pubmed: 29636357
Oncologist. 2005;10 Suppl 3:20-9
pubmed: 16368868
Stat Med. 2014 Dec 30;33(30):5388-98
pubmed: 24980445
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Ann Oncol. 2015 May;26(5):873-879
pubmed: 25725046
J Biol Chem. 2013 Aug 16;288(33):24020-34
pubmed: 23814048
Commun Biol. 2020 Mar 13;3(1):126
pubmed: 32170217
Int J Gynecol Cancer. 2019 Oct;29(8):1280-1284
pubmed: 31570543
Cell Death Dis. 2017 Mar 23;8(3):e2691
pubmed: 28333147
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Cancer Res. 2019 Sep 1;79(17):4399-4411
pubmed: 31289134
Arch Intern Med. 1983 Jul;143(7):1347-9
pubmed: 6347109
Breast Cancer Res. 2009;11(6):R81
pubmed: 19903352
Gut. 2016 Apr;65(4):635-46
pubmed: 25947013
ACS Nano. 2019 Jun 25;13(6):6396-6408
pubmed: 31187975
Epigenomics. 2019 Nov;11(14):1561-1579
pubmed: 31584294
Eur Rev Med Pharmacol Sci. 2013 Aug;17(16):2159-65
pubmed: 23893181
Comput Struct Biotechnol J. 2021 Jul 18;19:4101-4109
pubmed: 34527184
J Natl Cancer Inst. 2000 Jun 21;92(12):994-1000
pubmed: 10861311
Am Psychol. 2015 Feb-Mar;70(2):186-97
pubmed: 25730724
Clin Cancer Res. 2008 Apr 15;14(8):2502-10
pubmed: 18413843
Cancer Res. 2010 Sep 15;70(18):7042-52
pubmed: 20823155