Immune Landscape of Gastric Carcinoma Tumor Microenvironment Identifies a Peritoneal Relapse Relevant Immune Signature.
Adult
Aged
Aged, 80 and over
Carcinoma
/ epidemiology
Chemotherapy, Adjuvant
Female
Follow-Up Studies
Gastrectomy
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
/ immunology
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Nomograms
Peritoneal Neoplasms
/ epidemiology
Progression-Free Survival
ROC Curve
Retrospective Studies
Risk Assessment
/ methods
Stomach
/ immunology
Stomach Neoplasms
/ genetics
Tumor Microenvironment
/ genetics
Young Adult
LASSO
TME
gastric cancer
immune signature
peritoneal relapse
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
01
2021
accepted:
20
04
2021
entrez:
31
5
2021
pubmed:
1
6
2021
medline:
25
9
2021
Statut:
epublish
Résumé
Gastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC. In this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated A peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively. Overall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.
Sections du résumé
Background
Gastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.
Methods
In this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated
Results
A peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.
Conclusion
Overall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.
Identifiants
pubmed: 34054812
doi: 10.3389/fimmu.2021.651033
pmc: PMC8155484
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
651033Informations de copyright
Copyright © 2021 Zhang, Li, Yu, Li, Song, Chen, Fan, Liu and Qu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Nature. 2019 Jul;571(7763):E2
pubmed: 31227820
Recent Pat Anticancer Drug Discov. 2016;11(2):236-44
pubmed: 26817615
Front Cell Dev Biol. 2017 Mar 07;5:18
pubmed: 28326306
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Immune Netw. 2015 Dec;15(6):269-77
pubmed: 26770181
Oncol Rep. 2015 Aug;34(2):639-47
pubmed: 26081040
Cancer Res. 2011 May 15;71(10):3540-51
pubmed: 21430066
Science. 2015 Nov 20;350(6263):985-90
pubmed: 26494174
Cancer Res. 2015 Nov 1;75(21):4517-26
pubmed: 26329536
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
Nat Rev Immunol. 2016 Feb;16(2):112-23
pubmed: 26806484
Blood. 2011 Apr 28;117(17):4501-10
pubmed: 21385853
Ann Oncol. 2016 Sep;27(suppl 5):v38-v49
pubmed: 27664260
Cochrane Database Syst Rev. 2015 Feb 06;(2):CD009944
pubmed: 25914908
Nat Med. 2015 May;21(5):449-56
pubmed: 25894828
Oncol Rep. 2018 Sep;40(3):1287-1296
pubmed: 30015970
Br J Cancer. 2008 Nov 18;99(10):1704-11
pubmed: 18941457
Oncology. 2020;98(7):501-511
pubmed: 32380498
Oncol Lett. 2020 Dec;20(6):360
pubmed: 33133260
World J Surg Oncol. 2011 Jul 14;9:75
pubmed: 21752303
J Exp Clin Cancer Res. 2020 Oct 20;39(1):221
pubmed: 33081836
J Immunol Res. 2015;2015:308574
pubmed: 26579545
Abdom Imaging. 2015 Jun;40(5):1213-22
pubmed: 25348732
Gut Liver. 2014 Mar;8(2):131-9
pubmed: 24672653
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Ann Oncol. 2016 Apr;27(4):687-92
pubmed: 26787231
Clin Transl Oncol. 2014 Mar;16(3):257-65
pubmed: 23793812
Oncoimmunology. 2015 Jun 3;5(2):e1054598
pubmed: 27057426
Clin Cancer Res. 2016 Jun 15;22(12):2969-80
pubmed: 26755531
Br J Cancer. 2019 Dec;121(12):1058-1068
pubmed: 31754264
World J Gastroenterol. 2015 Oct 7;21(37):10502-9
pubmed: 26457011
Eur Radiol. 2012 Jul;22(7):1479-87
pubmed: 22358428
Nat Med. 2015 Aug;21(8):938-945
pubmed: 26193342
Appl Microbiol Biotechnol. 2012 Oct;96(1):211-20
pubmed: 22526791
Oncogene. 2008 Oct 6;27(45):5904-12
pubmed: 18836471
Cancer Res. 2021 Feb 15;81(4):986-1000
pubmed: 33310726
Cell Rep. 2016 May 31;15(9):2000-11
pubmed: 27210762
Oncogenesis. 2020 Jul 6;9(7):63
pubmed: 32632106
BMC Cancer. 2020 Oct 20;20(1):1014
pubmed: 33081727
Br J Radiol. 2019 May;92(1097):20181044
pubmed: 30789792
Gut. 2017 May;66(5):794-801
pubmed: 26801886
Br J Surg. 2000 Feb;87(2):236-42
pubmed: 10671934
Ann Surg Oncol. 2010 Sep;17(9):2370-7
pubmed: 20336386
Oncoimmunology. 2020 Jan 30;9(1):1708064
pubmed: 32076578
Cancer Cell. 2016 Aug 8;30(2):243-256
pubmed: 27505671
Nature. 2017 Apr 13;544(7649):250-254
pubmed: 28371798
Gastric Cancer. 2012 Sep;15 Suppl 1:S3-18
pubmed: 21837458
Int J Mol Sci. 2016 Nov 15;17(11):
pubmed: 27854307
J Immunother Cancer. 2020 Jun;8(1):
pubmed: 32601081
J Cancer. 2017 Feb 10;8(3):363-370
pubmed: 28261336
J Cancer. 2019 Aug 29;10(22):5377-5387
pubmed: 31632482
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Oncotarget. 2017 Mar 28;8(13):20741-20750
pubmed: 28186964
J Immunol Res. 2018 May 29;2018:4180517
pubmed: 30003113
Immunol Res. 2014 Jan;58(1):118-24
pubmed: 24402773
Oncoimmunology. 2012 Nov 1;1(8):1323-1343
pubmed: 23243596
Cancer Immunol Res. 2019 May;7(5):737-750
pubmed: 30842092
Gastric Cancer. 2016 Apr;19(2):466-471
pubmed: 26210691
Nat Rev Cancer. 2012 Mar 15;12(4):298-306
pubmed: 22419253
Anticancer Res. 2015 Jun;35(6):3511-8
pubmed: 26026118
Immunity. 2013 Oct 17;39(4):782-95
pubmed: 24138885
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Gastric Cancer. 2012 Jan;15(1):27-33
pubmed: 21626292
Oncoimmunology. 2017 Dec 21;7(3):e1356144
pubmed: 29399387
Cell Death Dis. 2019 Jul 31;10(8):574
pubmed: 31366904
BMC Cancer. 2018 Dec 17;18(1):1261
pubmed: 30558575
Biomater Sci. 2018 Sep 25;6(10):2704-2713
pubmed: 30151505
Br J Surg. 2018 Sep;105(10):1338-1348
pubmed: 29691839
Am J Cancer Res. 2020 Mar 01;10(3):1026-1044
pubmed: 32266108
Cancer Cell. 2017 Aug 14;32(2):135-154
pubmed: 28810142
Nat Rev Immunol. 2011 Aug 26;11(10):645-57
pubmed: 21869816
Ann Surg Oncol. 2019 Mar;26(3):876-883
pubmed: 30565045
J Exp Med. 2010 Sep 27;207(10):2187-94
pubmed: 20819927
Ann Surg Oncol. 2011 Jun;18(6):1575-81
pubmed: 21431408
Nat Rev Immunol. 2016 Oct;16(10):599-611
pubmed: 27526640
J Surg Oncol. 1995 Aug;59(4):226-9
pubmed: 7630168
Mol Cell Biol. 2014 Mar;34(5):888-99
pubmed: 24366546
Stat Med. 1997 Feb 28;16(4):385-95
pubmed: 9044528
Ann Surg. 2018 Mar;267(3):504-513
pubmed: 28002059
J Clin Oncol. 2019 Aug 10;37(23):2028-2040
pubmed: 31084544
Cancer Commun (Lond). 2019 Mar 18;39(1):10
pubmed: 30885279
Gut. 2020 Jan;69(1):18-31
pubmed: 31171626
Cancers (Basel). 2020 May 29;12(6):
pubmed: 32485933