Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity in tumor‑related genes in gastric cancer

Abstract

Microsatellite instability (MSI) detection is widely used in the diagnosis and prognosis evaluation of colorectal cancer. However, for gastric cancer (GC), there is no standard panel of microsatellites (MSs) used in clinical guidance. The present study aimed to identify useful predictors of the clinical features and for the prognosis of GC, based on an investigation of MSI and loss of heterozygosity (LOH) in tumor-related genes. First, from 20 tumor-related genes which were proven to be important to the development of GC, 91 MSs were identified, and PCR amplification, short tandem repeat scanning analysis and TA clone sequencing were used to analyze MSI and LOH in the first set of 90 GC samples. Subsequently, the same method was used to detect the MSI/LOH of the optimized loci in the second set of 136 GC samples. MSI/LOH in the mismatch repair genes was highly consistent with that in oncogenes and tumor suppressor genes, respectively. The length of the core sequence was a main factor for the MSI/LOH rate. The MSI of 12 single loci was significantly associated with lymph node metastasis. The MSI in TP53-1 and the LOH in MGMT-10 were significantly associated with early stages of tumor infiltration depth. The LOH in MGMT-10, PTN-2 and MCC-17 was significantly associated with TNM stage. The LOH in TP53-1 and ERBB2-12 was associated with adenocarcinoma. The MSI/LOH in 6 single loci of 5 tumor-related genes was associated with poor prognosis of GC. The present study demonstrated that the MSI/LOH of loci in tumor-associated genes was associated with 4 clinicopathological characteristics and outcomes of GC. These results may provide potential specific biomarkers for the clinical prediction and treatment of GC.

Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study

“…Based on the obtained results, a frequency of 7.5% (4 out of 53 GC patients) exhibited MSI-H phenotype. Although this incidence is relatively lower than the reported prevalence of MSI-H in GC patients by ACRG and TCGA, it is consistent with those reporting a prevalence of less than 10% (Table 2 ) in other populations worldwide 4 , 23 – 29 . As for the Middle Eastern countries, a prevalence of 11.6% has been reported in Turkey 30 .…”

“… # MSI-H Samples Clinicopathological Variables Refs. Older Ages Female Sex Intestinal Subtype TNM Stage Less Lymph Node Involvement Differentiation Distal Location Bigger Size 1 7.5% 226 0.074 NA NA NA 0.0036 NA NA NA 4 2 5.6% 414 0.010 NA 0.028 Increased T stage (0.009) NA NA NA 0.014 23 3 8.5% 1990 0.001 < 0.001 < 0.001 Lower tumor stage (0.001) NA Differentiated histological type (0.001) 0.001 NA 26 4 8.1% 310 0.008 - 0.003 NA – – – – 27 5 …”

“…This aligns with similar results presented in previous studies. For instance, Huo et al 4 reported a significant association between MSI-H and the absence of lymph node involvement (p-value = 0.0036). Additionally, Lee et al 44 demonstrated a significant association between MSI-H and a lower prevalence of lymph node metastasis (p-value = 0.004).…”

“…Furthermore, GC has been identified as a complex and heterogeneous disease. Evidence indicates that GC prognosis and treatment outcomes depend not only on the tumor stage, but also on the molecular and genetic features 4 , 5 . Different classifications have been introduced for GC.…”

Concordance between microsatellite instability testing and immunohistochemistry for mismatch repair proteins and efficient screening of mismatch repair deficient gastric cancer

“…Mononucleotide markers are generally more sensitive in the West (21,22). However, compared with data from Western countries, several reports from Asia suggest that the dinucleotide region is often unstable in GCs and that D2S123 is particularly sensitive (33,34). Although the involvement of Helicobacter pylori is suspected as a hallmark of GC in East Asia, its status as a causative factor remains uncertain because some reports have shown no relationship between H. pylori and MSI (35).…”