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Gastric Cancer Subtypes Found to Have Different Prognoses

NEW YORK (GenomeWeb) – The four subtypes of gastric cancer identified by the Cancer Genome Atlas project are associated with different prognoses, according to a new study.

In 2014, researchers from TCGA reported that they uncovered different molecular types of gastric cancer: one that was associated with Epstein-Barr virus infection, one with microsatellite instability, another with chromosomal instability, and one with genomic stability.

In a new study appearing in Clinical Cancer Research today, researchers from the US and South Korea found that gastric tumors could be classified into these four subtypes based on their gene expression patterns. Additionally, they reported that the EBV subtype was associated with the best prognosis and that the chromosomal instability subtype was the most likely to respond to adjuvant chemotherapy treatment.

"These findings, if confirmed, could provide some information for personalized medicine," senior author Ju-Seog Lee from the University of Texas MD Anderson Cancer Center said in a statement. "As we learn more about the biological characteristics associated with each subtype, it will help determine which patients will benefit from immunotherapy, chemotherapy, or other treatment options."

Lee and his colleagues examined gene expression data generated by TCGA for 262 gastric tumors and developed subtype-specific signatures for each.

In particular, they bundled the top 200 significant genes for the EBV, MSI, and GS subtypes and all 143 significant genes for the CIN subtype into four Bayesian prediction algorithms. The EBV prediction signature had the highest sensitivity and specificity, with an area under the curve of 100 percent, while the CIN prediction signature had the lowest, with an area under the curve of 89.6 percent, the researchers reported.

They applied these gene expression-based prediction models to two cohorts, one of 267 patients from MD Anderson and one of 432 patients from the Samsung Medical Center, and correlated the subtype categorization with prognosis.

In the MD Anderson cohort, the EBV subtype was associated with better recurrence-free survival and overall survival, while the GS subtype was associated with the worst prognosis. The MSI and CIN subtypes fell in the middle, they noted.

Similarly in the Samsung cohort, the EBV subtype was associated with the best prognosis and GS with the worst. Again, MSI was linked to a moderate prognosis, but the prognosis associated with the CIN subtype was markedly worse in this cohort, according to the researchers. They suggested that the CIN subtype might be more heterogeneous.

By combining the four subtype predictors, he and his colleagues developed an integrated risk assessment model they dubbed TCGA Risk Score (TRS). When they applied it to the combined MD Anderson and Samsung cohort, they found that the five-year recurrence-free survival rate was 66.7 percent for low-risk patients, 52.1 percent for intermediate-risk patients, and 37.5 percent for high-risk patients.

Patients with the GS subtype had the highest TRS value, while those with the EBV subtype had the lowest, they noted.

The researchers likewise examined how the subtypes tended to respond to treatment. They reported that patients with the CIN subtype exhibited the greatest benefit from adjuvant chemotherapy treatment and had a three-year recurrence-free survival rate of 58.7 percent for those who received chemotherapy versus 33.5 percent for those who did not.

Patients with the GS subtype, however, appeared to receive no benefit from chemotherapy treatment. "This means that we need to find novel targets and drugs for this subtype," Lee said.