Researchers have identified microbiota signatures that are associated with KRAS mutations in patients with colorectal cancer, according to a recent study published by Huang et al in Microbiology Spectrum. The findings suggest that gut microbes may serve as a noninvasive biomarker for subtypes of colorectal cancer and may inform personalized treatment approaches.
Background
Colorectal cancer is the third most common cancer type and the second leading cause of cancer mortality. Each year, nearly 2 million patients are diagnosed with colorectal cancer and over 900,000 die from the disease globally, according to the World Health Organization. Previous studies have demonstrated that gut bacterial imbalances may be connected to the formation and spread of colorectal cancer, suggesting that a closer examination of the gut microbial populations in the context of colorectal cancer could yield new insights about diagnosis and treatment.
About 40% of all colorectal cancer tumors carry KRAS mutations, which have been linked to shorter survival and more aggressive disease. The onset and growth of colorectal cancer has also been associated with imbalances in the gut microbiome; however, the interplay between gut dysbiosis and KRAS mutations remains poorly understood.
“Understanding the specific associations between different types of KRAS mutations and [colorectal cancer] is vital for several reasons,” emphasized lead study author Zigui Huang, a medical student at the Guangxi Medical University Cancer Hospital. For instance, the associations can help researchers elucidate the molecular mechanisms that drive the development of colorectal cancer and identify biomarkers for diagnosis and disease progression.
Study Methods and Results
In the recent study, the researchers used 16s rRNA sequencing to analyze the stool samples of 94 patients with colorectal cancer—24 of whom had KRAS-mutated tumors and 70 of whom had nonmutated tumors. The researchers identified 26 different types of gut microbiota that were present in the KRAS-mutated colorectal cancer group of patients but not in the nonmutated colorectal cancer group. Bacteria of the genera Fusobacterium—which has been previously correlated with the development of colorectal cancer—Clostridium, and Shewanella were all abundant in the patients with KRAS-mutated disease. They noted that all three types of bacteria could be used as noninvasive biomarkers to determine patients’ KRAS status.
Additionally, the genera Bifidobacterium and Akkermansia were abundant in the patients without KRAS mutations and have shown probiotic activities in prior research—including suppression of proinflammatory factors in the colon. The researchers hypothesized that the presence of these bacteria may reduce a patient’s risk of developing a KRAS mutation and slow the progression of colorectal cancer.
The investigators also introduced a machine learning model that could use the data from their study to guide personalized treatment recommendations based on microbiota signatures. Nonetheless, they stressed that the model may require data from a larger group of patients to improve its efficacy.
Conclusions
The researchers plan to conduct larger studies to validate their recent findings, better understand the significance of gut microbiota, and improve treatment options in patients with colorectal cancer.
“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” highlighted co–study author Tang Weizhong, MD, an oncologist at the Guangxi Medical University Cancer Hospital. “This study aligns with our broader research focus on understanding the intricate interplay between genetic mutations, the tumor microenvironment, and gut microbiota in colorectal cancer,” he concluded.
Disclosure: For full disclosures of the study authors, visit journals.asm.org.
