Leveraging Fecal Bacterial Survey Data to Predict Colorectal Tumors.

Bangzhou Zhang,Wei Xu,Qiongyun Chen,Jianlin Ren,Chuanxing Xiao,Zhangran Chen,Hongzhi Xu,Jie Yang,Qi Liu,Jinfeng Yang,Huangkai Zhang,Yanyun Fan,Shuangbin Xu,Changsheng Yan

doi:10.3389/fgene.2019.00447

Abstract

Colorectal cancer (CRC) ranks second in cancer-associated mortality and third in the incidence worldwide. Most of CRC follow adenoma-carcinoma sequence, and have more than 90% chance of survival if diagnosed at early stage. But the recommended screening by colonoscopy is invasive, expensive, and poorly adhered to. Recently, several studies reported that the fecal bacteria might provide non-invasive biomarkers for CRC and precancerous tumors. Therefore, we collected and uniformly re-analyzed these published fecal 16S rDNA sequencing datasets to verify the association and identify biomarkers to classify and predict colorectal tumors by random forest method. A total of 1674 samples (330 CRC, 357 advanced adenoma, 141 adenoma, and 846 control) from 7 studies were analyzed in this study. By random effects model and fixed effects model, we observed significant differences in alpha-diversity and beta-diversity between individuals with CRC and the normal colon, but not between adenoma and the normal. We identified various bacterial genera with significant odds ratios for colorectal tumors at different stages. Through building random forest model with 10-fold cross-validation as well as new test datasets, we classified individuals with CRC, advanced adenoma, adenoma and normal colon. All approaches obtained comparable performance at entire OTU level, entire genus level, and the common genus level as measured using AUC. When combined all samples, the AUC of random forest model based on 12 common genera reached 0.846 for CRC, although the predication performed poorly for advance adenoma and adenoma.

Highlights

Colorectal cancer (CRC) ranks second in term of cancer-associated mortality and third in term of incidence, with an estimation of 881000 deaths and over 1.8 million new cases in 2018 in both sexes globally (Bray et al, 2018)
We conducted a comprehensive meta-analysis on a diverse collection of 16S rDNA sequencing studies with relatively higher sequencing depth from 6 countries to reveal the great differences in fecal bacterial communities in individuals with colorectal tumors and normal colons
By analyzing all datasets in a uniform manner, we further identified and validated fecal bacterial biomarkers and their important roles in classifying subjects with colorectal tumors, especially the CRC and the normal control

Summary

Introduction

Colorectal cancer (CRC) ranks second in term of cancer-associated mortality and third in term of incidence, with an estimation of 881000 deaths and over 1.8 million new cases in 2018 in both sexes globally (Bray et al, 2018). CRC incidence rates are about 3-fold higher in developed countries than developing ones. The incidence and mortality rates showed an increasing trend in China in the past decades. The age-standardized incidence and mortality rates by world standard population are 17.52 and 7.91 per 100000 in 2014, respectively (Chen W. et al, 2018). Predicting Colorectal Tumors exceeds 90% if the cancer is detected at early stage, but decreases to 13% with advanced metastatic disease (Shah et al, 2018). Targeting the CRC by early screening and treatment, especially as early to the adenoma stage, would have profound clinical and socioeconomic significances

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Conclusion