GW researchers find connection between microbiome composition and colon cancer

By Katherine Shagoury

A mutant protein found in humans with colon cancer blocks a pathway that regulates proliferation and expansion of cells, increasing amounts of bacterial species associated with the development of colon cancer, according to new research from George Washington University (GW) in Washington, DC and published in the journal Gastroenterology.

Researchers led by Mishra, MD, director of the Center for Translational Medicine at the GW Cancer Center and professor of surgery at the GW School of Medicine and Health Sciences, looked at the interactions among proteins of the carcinoembryonic antigen related cell adhesion molecular (CAECAM) family, which interact with microbes, leading to changes in the growth factor beta (TGFB) signaling pathway.

The team collected data on DNA sequences, mRNA expression levels, and patient survival times from 456 colorectal adenocarcinoma cases, and a separate set of 594 samples of colorectal adenocarcinomas, in The Cancer Genome Atlas. The team then used the GW Genomics Core to perform shotgun metagenomic sequencing analysis of feces from mice with defects in TGFB signaling to identify changes in the microbiome before colon tumors developed.

Researchers also found that the expression of CEACAMs and genes that regulate stem cell features of cells are increased in colon cancer and inversely correlated with expression of TGFB pathway genes. They also found colon cancer to express mutant forms of CEACAM5 that inhibit TGFB signaling and increase proliferation and colony formation.

Colon cancer is increasing in young people, Mishra said. Current guidelines recommend screening those over age 50 for colon cancer, but today we are seeing that 15 percent of those with colon cancer are under the age of 50. The findings could lead to less invasive screening techniques for colon cancer, particularly for younger patients, according to Mishra.  

“We hypothesized that diet and its effects on the microbiome may be big players,” Mishra said.