Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 11 2022
09 11 2022
Historique:
received:
16
03
2022
accepted:
18
10
2022
entrez:
9
11
2022
pubmed:
10
11
2022
medline:
15
11
2022
Statut:
epublish
Résumé
Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.
Identifiants
pubmed: 36351995
doi: 10.1038/s41598-022-22685-0
pii: 10.1038/s41598-022-22685-0
pmc: PMC9646713
doi:
Substances chimiques
CD274 protein, human
0
B7-H1 Antigen
0
Keratin-7
0
Biomarkers, Tumor
0
SATB2 protein, human
0
Transcription Factors
0
Matrix Attachment Region Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19152Subventions
Organisme : Agentura Pro Zdravotnický Výzkum České Republiky
ID : NU21J-03-00019
Organisme : Grantová Agentura České Republiky
ID : 21-27902S
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : VFN, 00064165
Informations de copyright
© 2022. The Author(s).
Références
Virchows Arch. 2015 Apr;466(4):383-91
pubmed: 25665656
Mod Pathol. 2016 Nov;29(11):1433-1442
pubmed: 27443512
Br J Cancer. 2019 Oct;121(7):593-599
pubmed: 31474758
EMBO Rep. 2010 Oct;11(10):777-83
pubmed: 20829881
Mod Pathol. 2021 Sep;34(9):1719-1727
pubmed: 34002009
Crit Rev Oncol Hematol. 2021 Jan;157:103147
pubmed: 33278675
J Cancer Res Clin Oncol. 2019 Jul;145(7):1785-1794
pubmed: 31129768
Mod Pathol. 2008 Nov;21(11):1403-12
pubmed: 18587323
Hum Mol Genet. 2003 Oct 1;12(19):2491-501
pubmed: 12915443
Am J Surg Pathol. 2018 Feb;42(2):160-171
pubmed: 28914716
Oncoimmunology. 2018 Jun 11;7(8):e1465165
pubmed: 30221062
Acta Oncol. 2020 Mar;59(3):284-290
pubmed: 31769323
Anticancer Res. 2015 Oct;35(10):5369-76
pubmed: 26408698
Cancer Sci. 2016 Jun;107(6):726-33
pubmed: 27015293
Am J Surg Pathol. 2011 Jul;35(7):937-48
pubmed: 21677534
Breast. 2021 Dec;60:238-244
pubmed: 34768219
Cancer Immunol Immunother. 2017 May;66(5):551-564
pubmed: 28213726
Hum Pathol. 2014 Aug;45(8):1704-12
pubmed: 24908142
Diagn Pathol. 2012 Jan 23;7:9
pubmed: 22268990
Int J Colorectal Dis. 2012 Feb;27(2):143-50
pubmed: 21870058
Histopathology. 2013 Jul;63(1):36-49
pubmed: 23701429
Mod Pathol. 2016 Sep;29(9):1104-12
pubmed: 27198569
Cancer Res Treat. 2020 Jul;52(3):661-670
pubmed: 32019283
Br J Cancer. 2002 Jun 17;86(12):1884-7
pubmed: 12085180
Virchows Arch. 2001 Oct;439(4):512-22
pubmed: 11710638
Histopathology. 2011 Aug;59(2):225-34
pubmed: 21884201
J Cancer. 2018 Oct 21;9(23):4325-4333
pubmed: 30519336
PLoS One. 2013 Oct 04;8(10):e76012
pubmed: 24124529
Int J Clin Exp Pathol. 2015 Sep 01;8(9):11084-91
pubmed: 26617827
J Immunother Cancer. 2018 Jan 23;6(1):8
pubmed: 29357948
Ann Surg. 2019 Mar;269(3):471-478
pubmed: 29206673
Nature. 2008 Mar 13;452(7184):187-93
pubmed: 18337816
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Arch Pathol Lab Med. 2014 Aug;138(8):1015-26
pubmed: 24437456
BMC Cancer. 2019 Feb 12;19(1):142
pubmed: 30755167
Sci Rep. 2021 Sep 9;11(1):17863
pubmed: 34504224
Cancer Sci. 2018 Sep;109(9):2957-2969
pubmed: 29949671
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Hum Pathol. 2005 Mar;36(3):275-81
pubmed: 15791572
Cell Stem Cell. 2022 Jan 6;29(1):101-115.e10
pubmed: 34582804
Int J Colorectal Dis. 2021 Jan;36(1):117-130
pubmed: 32910207
J Clin Pathol. 2021 Nov;74(11):735-740
pubmed: 33589532
Appl Immunohistochem Mol Morphol. 2009 May;17(3):196-201
pubmed: 19098678
Cancer Sci. 2017 May;108(5):853-858
pubmed: 28267224
Virchows Arch. 2020 Nov;477(5):687-696
pubmed: 32424767
PLoS One. 2017 Aug 10;12(8):e0182692
pubmed: 28796808
J Cancer Res Clin Oncol. 2019 Apr;145(4):1043-1053
pubmed: 30874889
Hum Pathol. 2002 Nov;33(11):1078-85
pubmed: 12454811
Appl Immunohistochem Mol Morphol. 2003 Dec;11(4):306-10
pubmed: 14663355
J Pathol. 2009 Sep;219(1):114-22
pubmed: 19557828
Biomed Res Int. 2020 Jan 25;2020:9037217
pubmed: 32090113
Cancer Manag Res. 2017 Jun 29;9:249-258
pubmed: 28721097
Cell Biol Int. 2020 May;44(5):1224-1236
pubmed: 32068322
Cell. 2006 Jun 2;125(5):971-86
pubmed: 16751105
Pathol Res Pract. 2012 Mar 15;208(3):163-6
pubmed: 22361037
Clin Colorectal Cancer. 2019 Mar;18(1):e20-e38
pubmed: 30389315
Pathol Res Pract. 2011 Mar 15;207(3):156-60
pubmed: 21282015
Anticancer Res. 2018 Jun;38(6):3367-3373
pubmed: 29848685
Mol Cancer. 2016 Aug 24;15(1):55
pubmed: 27552968
Medicina (Kaunas). 2019 Oct 31;55(11):
pubmed: 31683723
Cancers (Basel). 2021 Dec 07;13(24):
pubmed: 34944797
World J Surg Oncol. 2019 Jan 4;17(1):4
pubmed: 30609938
Am J Hum Genet. 2006 Oct;79(4):668-78
pubmed: 16960803
Arch Pathol Lab Med. 2017 Oct;141(10):1428-1433
pubmed: 28968158
J Gastroenterol Hepatol. 2013 Dec;28(12):1815-22
pubmed: 23808938
Gastric Cancer. 2016 Apr;19(2):466-471
pubmed: 26210691
Cancer Immunol Immunother. 2017 Jul;66(7):927-939
pubmed: 28405764
Hum Pathol. 2018 Nov;81:157-165
pubmed: 30031096
Am J Clin Pathol. 2014 May;141(5):630-8
pubmed: 24713733
Eur J Cancer. 2018 Mar;91:11-20
pubmed: 29328976
Saudi J Gastroenterol. 2018 Mar-Apr;24(2):129-134
pubmed: 29637921
Genes Dev. 2003 Dec 15;17(24):3048-61
pubmed: 14701874
Dent J (Basel). 2021 Dec 30;10(1):
pubmed: 35049602
Br J Cancer. 2012 Feb 28;106(5):931-8
pubmed: 22333599
Am J Surg Pathol. 2018 Dec;42(12):1715-1722
pubmed: 30212392
Lancet Oncol. 2017 Sep;18(9):1182-1191
pubmed: 28734759
JAMA Oncol. 2019 Aug 01;5(8):1195-1204
pubmed: 31318407
Oncologist. 2016 May;21(5):643-50
pubmed: 27026676
Biomed Res Int. 2019 Jun 03;2019:8014627
pubmed: 31275983
J Cancer. 2019 Jun 2;10(11):2510-2519
pubmed: 31258757
Histopathology. 2022 Dec;81(6):732-741
pubmed: 35993150
Virchows Arch. 2003 Aug;443(2):115-21
pubmed: 12802583
Int J Clin Oncol. 2016 Oct;21(5):946-952
pubmed: 26919982
Int J Clin Exp Pathol. 2015 Aug 01;8(8):9351-9
pubmed: 26464688
Am J Surg Pathol. 2004 Jun;28(6):712-8
pubmed: 15166663