Research paves way for improved colorectal cancer test

April 19, 2017

The type of bacteria in your gut may help diagnose colorectal cancer. Researchers at Baylor College of Medicine and other institutions have identified specific types of bacteria that seem to be abundant in individuals with colorectal cancer. Using a combination of markers specific for these fecal microbes, scientists anticipate that a noninvasive, sensitive clinical diagnostic test potentially can be developed. The study is published in Gut.

Colorectal cancer is the second-leading cause of cancer-associated death in the United States. Individuals diagnosed early have a 90 percent chance of survival; however, more than 30 percent of individuals 50 years old or older, the high-risk group, indicate never having been screened for the disease. Currently, recommended screening methods include an invasive procedure - colonoscopy - and noninvasive tests, such as home-based fecal occult blood tests, and Cologuard for detecting colorectal cancer DNA markers and blood in stools. Each of these methods has its shortcomings, so to meet the need for a sensitive, noninvasive diagnostic test for colorectal cancer, the team of researchers looked at gut microbes as indicators of the disease.

"A number of studies have shown an association between fecal microbes and colorectal cancer; however, there is limited agreement in the types of microbes reported," said first author Dr. Manasi Shah, who was a graduate student at the University of Texas School of Public Health during the course of this project. "I was interested in finding a microbial marker for the disease. One way to do this is by carrying out a single-institution study, but this takes a long time for sample collection, involves sequencing the microbes' DNA and is expensive. I noticed that some of the published studies provided the means for accessing the raw microbial DNA sequencing data of the samples. How great it would be, I thought, if I could leverage existing raw data across multiple cohorts and come up with a generalizable marker for the disease." Shah realized that to take this approach, in addition to her biostatistical training, she would need to learn the bioinformatics tools necessary for analyzing next generation sequencing data. She approached senior author Dr. Emily Hollister, assistant professor of pathology at Baylor and Texas Children's Hospital and director of microbial ecology for the Texas Children's Microbiome Center, proposed her idea and expressed interest in learning the tools required to reprocess microbial sequence data from its original format.

"Manasi had the interest, and we had the expertise," Hollister said. "In our center, we had been planning to compare a series of different statistical tools to analyze large amounts of microbiome data. Manasi's proposal fit very well with our goals."

Researchers reanalyzed raw bacterial DNA sequence data from several studies and confirmed previously reported types of bacteria associated with colorectal cancer and identified other bacteria not previously associated with the disease.

Easier said than done

"In our experience, collecting the raw data from the published studies was an uphill task," Shah said. "Some studies shared all the sample-associated microbial DNA sequences and clinical data, others only shared partial data or did not share any data at all. After much effort, I was able to gather data from nine of 12 published studies. This highlights the need for an initiative to encourage investigators to share their data upon publication, which will help wider dissemination and reproducibility in the field."

The researchers also had to overcome the difficulties posed by the diversity of technological approaches used by different laboratories analyzing the samples.

"This was an incredibly large, complex multinational study," said co-author Todd DeSantis, co-founder and vice president of informatics at Second Genome Inc. "We saw many differences between medical centers in the way each collected and stored stool samples and in the methods used to process the bacterial DNA in stools. These differences can be problematic for identifying the bacterial strains that proliferate in cancer patients, but our Second Genome KnowlegeBase Team, led by co-author Thomas Weinmaier, found ways to enhance our software platform to address these differences along the way. The findings that emerged from this challenging data set helped validate our platform, and in the process we were able to deliver high-quality insights to advance our collaboration with Dr. Hollister."

After reanalyzing large amounts of raw bacterial DNA sequence data from several studies uniformly using a variety of statistical tools, the scientists confirmed previously reported types of bacteria associated with colorectal cancer and identified other bacteria not previously associated with the disease.

"The fact that even when we combined several different studies we could correctly classify a sample as a colorectal cancer case or control with 80 percent accuracy solely based on microbial abundances was very encouraging," Shah said. "This is a promising first step to develop a noninvasive test that might be used in the detection of colorectal cancer, supplementing colonoscopy or fecal occult blood tests," Hollister said.

"The same strategy could be applied for developing diagnostic tests or therapeutics for other diseases such as inflammatory bowel disease, nonalcoholic steatohepatitis (a form of non-alcoholic fatty liver disease), type 2 diabetes and Alzheimer's disease, among others for which the microbiome is currently being investigated," Shah said.
Other contributors to this work include Paul J McMurdie, Julia L Cope, Adam Altrichter and José-Miguel Yamal. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the University of Texas School of Public Health, Texas Children's Hospital, Second Genome Inc, Whole Biome Inc and Diversigen Inc.

Baylor College of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to