Molecular pathogenesis of microsatellite instability-high early-stage colorectal adenocarcinoma in India.
Drug Metab Pers Ther
; 2024 Jul 24.
Article
en En
| MEDLINE
| ID: mdl-39042905
ABSTRACT
OBJECTIVES:
The prevalence of microsatellite instability (MSI) subtype among all colon cancers in India is about 30â¯%, approximately two times more than that of western population suggesting different molecular pathogeneses.METHODS:
A NanoString analysis-based Pan cancer differential expression (DE) profile was determined in a primary cohort of early-stage CRC (tumor=10, normal=7), and correlated against MSI status. Using RT-PCR, tumor-specific DE genes were validated in another cohort of MSI-high CRC (n=15).RESULTS:
Among the most differentially expressed genes, AXIN2, ETV4, and RNF43 were tumor cell-specific signals, while a set of genes including COL11A1, COMP, INHBA, SPP1, MMP3, TLR2, and others were immune cell-specific signals, that had a differential expression between MSI and MSS groups. When overlapped with The Cancer Genome Atlas (TCGA) studies using the Tumor immune estimation resource tool (TIMER), and protein-protein interaction analysis by STRING.db, these genes were segregated to representative tumor cells and immune cells. On validation, the tumor-specific gene signals were inversely associated with TLR4 expression.CONCLUSIONS:
The differential expression distribution of AXIN2, ETV4, and RNF43 among tumor and immune cells, suggests more than one pathological subset in the MSI-H subgroup of early-stage CRC in the Indian population.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Drug Metab Pers Ther
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Alemania