Abstract
Evaluating the risk of colorectal metachronous adenoma (MA), which is a precancerous lesion, is necessary for metachronous colorectal cancer (CRC) precaution among CRC patients who had underwent surgical removal of their primary tumor. Here, discovery cohort (n = 41) and validation cohort (n = 45) of CRC patients were prospectively enrolled in this study. Mucosal and fecal samples were used for gut microbiota analysis by sequencing the 16S rRNA genes. Significant reduction of microbial diversity was noted in MA (P < 0.001). A signature defined by decreased abundance of eight genera and increased abundance of two genera strongly correlated with MA. The microbiota-based random forest (RF) model, established utilizing Escherichia–Shigella, Acinetobacter together with BMI in combination, achieved AUC values of 0.885 and 0.832 for MA, predicting in discovery and validation cohort, respectively. The RF model was performed as well for fecal and tumor adjacent mucosal samples with an AUC of 0.835 and 0.889, respectively. Gut microbiota profile of MA still existed in post-operative cohort patients, but the RF model could not be performed well on this cohort, with an AUC of 0.61. Finally, we introduced a risk score based on Escherichia–Shigella, Acinetobacter and BMI, and synchronous-adenoma achieved AUC values of 0.94 and 0.835 in discovery and validation cohort, respectively. This study presented a comprehensive landscape of gut microbiota in MA, demonstrated that the gut microbiota-based models and scoring system achieved good ability to predict the risk for developing MA after surgical resection. Our study suggests that gut microbiota is a potential predictive biomarker for MA.
Highlights
Colorectal cancer (CRC) is among the leading cause of cancer-related deaths worldwide
Forty-one patients were included for discovery cohort, of which 22 patients developed metachronous adenoma (MA group), and the remaining 19 patients did not have any signs of metachronous adenoma [non-metachronous adenoma group]
The incidence of synchronous adenoma was significantly higher in the MA versus non-metachronous adenoma (nMA) groups (15/22 vs. 7/19; P < 0.05)
Summary
Colorectal cancer (CRC) is among the leading cause of cancer-related deaths worldwide. Despite substantial progress in the early diagnosis and treatment of CRC and the fact that more than two-thirds of CRC patients received surgical resection and adjuvant therapy, nearly 40% of these patients developed CRC recurrence, including local recurrence, metachronous cancer, and distant metastasis (Kahi et al, 2016). It has been well-documented that patients with a history of CRC are at an increased risk of developing metachronous CRC following surgical resection and preoperative clearing (Balleste et al, 2007; Mulder et al, 2012). There is no first-level evidence in support of the optimal total duration of surveillance after treatment for CRC (van der Stok et al, 2016)
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