SAN DIEGO – A panel of four fecal bacteria can reliably discriminate between colorectal cancer (CRC) patients and controls. Combining these four biomarkers with the fecal immunochemical test (FIT) further increases the sensitivity and specificity for CRC.
“This study establishes a reliable platform for a convenient translational approach of using new markers identified by a metagenomics approach. This panel, in combination with other modalities, may be useful for a noninvasive method of diagnosing CRC. Our data look most promising for the combination of FIT plus the four biomarkers,” Dr. Jessie Qiaoyi Liang said at a presentation during the annual Digestive Disease Week.
Dr. Jessica Liang
In this study, FIT had a sensitivity of 70.3% and a specificity of 98.3%. Using the four biomarkers led to a sensitivity of 83.8% and a specificity of 83.2%, while combining them with FIT achieved a sensitivity of 92.8% and a specificity of 81.5%.
The four bacteria included Fusobacterium nucleatum (Fn, a previously identified biomarker), as well as three newly described candidates: Bacteroides clarus (Bc), Clostridium hathewayi (Ch), and one undefined species (in-house label ‘m7’).
The study evaluated the utility of fecal bacterial marker candidates by metagenomic sequencing for the diagnosis of CRC using the simple, cost-effective and targeted method of quantitative PCR.
A strong correlation was observed between qPCR assays and the metagenomic approach for these candidate bacteria. The four bacteria were selected from 21 candidate bacteria. Each of the four candidates was analyzed separately and in combination to determine their utility for the diagnosis of CRC.
The four biomarkers were validated in stool samples from two cohorts of patients prior to undergoing colonoscopy: a Hong Kong cohort of 370 patients (170 found to have CRC and 200 controls) and a second cohort of Shanghai patients (total 69, 33 CRC patients and 36 controls).
All four were found to significantly discriminate between CRC and controls in both cohorts of patients
Next, the researchers looked at these four bacteria and compared them with Fn, m7, and Bc in a cohort of 230 subjects from Hong Kong – 111 with CRC and 119 controls. The four-bacteria panel was significantly better than the three-bacteria panel.
In that same cohort of patients, they compared FIT alone, the four bacteria panel alone, and the combination of the two. The four markers had higher sensitivity compared to FIT alone for stage 1 colorectal cancer, but sensitivity was similar to FIT for stages II, III, and IV.
Using both FIT and the four-bacteria panel increased the sensitivity from 70.3% for FIT to 92.8%.
“At this time, we can say this is promising research. The panel cannot be used in the clinical setting. We plan further studies. The combination of FIT plus the four biomarkers looks the most promising,” said Dr. Liang, a research assistant professor at the Chinese University of Hong Kong.
She noted that the panel is not discriminatory enough for adenoma patients. “We are still looking for other markers for adenomas,” she said.
Commenting on the state of the art for biomarkers in gastrointestinal cancer, Dr. Joseph Sung, Chinese University of Hong Kong, said that there are thousands of biomarkers under study.
“Combinations of biomarkers will turn out to be more useful. They should be used in combination with other diagnostic modules. Cancer biomarkers require large validation studies in different populations.
“We are unlikely to find a single magic bullet,” he said. “The list of biomarkers will continue to grow. All are undergoing larger-scale validation in centers in China, but we need to be cognizant that populations around the world will not have the same biomarkers. The real issue in microbiome markers is geographic variation,” he stated.