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Published on: March 10, 2015
MICA-129 Met/Met contributes to the susceptibility of colorectal cancer
Jingxin Ye1,2, Renan Chang3, Jianfeng Zhang4
1Department of Gastroenterology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, Jiangsu Province, China.
Abstract:
The highly polymorphic human major histocompatibility complex class I chain-related gene A (MICA) regulates immune surveillance and destroys tumor cells by activating its receptor, the natural killer group 2D. This study aimed to examine a single nucleotide polymorphism of this gene at codon 129 (MICA-129) in association with colorectal cancer (CRC). Using PCR sequencing, the MICA-129 polymorphism was examined in 104 patients with CRC and 536 healthy controls. Specific MICA-129 single nucleotide polymorphism was analyzed for its association with CRC susceptibility, clinical phenotypes, and selected CRC-associated microsatellite instability, driver gene mutation, immune checkpoint programmed death ligand 1, and diagnostic biomarkers carbohydrate antigen 19-9 and carcinoembryonic antigen. The MICA-129 heterozygous A/G (Met/Val) genotype was associated with less aggressive clinical characteristics, such as a reduced prevalence of the ulcerated subtype (P = .0489, OR = 0.59) and lymph node involvement (P = .0217, OR = 0.46). Conversely, the MICA-129 homozygous allele A/A (Met/Met) variant was related to more advanced clinical characteristics, such as increased tumor invasion depth (T3/4; P = .0261, OR = 2.10), driver gene mutation (P = .0363, OR = 2.65), and KRAS mutation (P = .0392, OR = 2.23). Additionally, patients with carbohydrate antigen 19-9-positive CRC had a lower MICA-129 Met/Val variation, whereas those with carcinoembryonic antigen-positive CRC had a higher MICA-129 Met/Met variant (P = .0330/OR = 0.22 and P = .0034/OR = 2.99, respectively).
Insights
The MICA-129 polymorphism influences colorectal cancer (CRC) aggressiveness. The heterozygous MICA-129 Met/Val genotype correlates with less aggressive CRC, while the homozygous Met/Met variant is linked to more advanced disease characteristics.
Area of Science:
- Immunogenetics
- Cancer Biology
- Molecular Oncology
Background:
- The human major histocompatibility complex class I chain-related gene A (MICA) is crucial for immune surveillance and tumor cell destruction via the natural killer group 2D receptor.
- MICA exhibits high polymorphism, with single nucleotide polymorphisms (SNPs) potentially influencing cancer susceptibility and progression.
Purpose of the Study:
- To investigate the association between a specific MICA single nucleotide polymorphism at codon 129 (MICA-129) and colorectal cancer (CRC).
- To analyze the relationship between MICA-129 polymorphism and CRC susceptibility, clinical phenotypes, and relevant molecular/diagnostic markers.
Main Methods:
- PCR sequencing was employed to genotype the MICA-129 polymorphism in 104 CRC patients and 536 healthy controls.
- Statistical analyses were performed to assess associations with CRC susceptibility, clinical characteristics, microsatellite instability, driver gene mutations (including KRAS), programmed death ligand 1 expression, and tumor biomarkers (carbohydrate antigen 19-9 and carcinoembryonic antigen).
Main Results:
- The MICA-129 heterozygous Met/Val genotype was associated with less aggressive clinical features, including reduced ulcerated subtype prevalence and lymph node involvement.
- The homozygous Met/Met variant correlated with more advanced characteristics, such as increased tumor invasion depth, overall driver gene mutations, and KRAS mutations.
- MICA-129 Met/Val variation was lower in carbohydrate antigen 19-9-positive CRC, while the Met/Met variant was higher in carcinoembryonic antigen-positive CRC.
Conclusions:
- The MICA-129 polymorphism plays a significant role in modulating colorectal cancer aggressiveness and clinical presentation.
- Specific MICA-129 genotypes may serve as potential indicators for CRC progression and response to certain biomarkers.
