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Chen MX, Ge QW, Li XY, Dai WJ, Wang HG. Size-dependent transcriptomic heterogeneity and microbial dysbiosis in Peutz-Jeghers syndrome colorectal polyps: An exploratory self-controlled multi-omics analysis. World J Gastrointest Oncol 2026; 18(12): 124550 [DOI: 10.4251/wjgo.124550]
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 124550 Published online Dec 15, 2026. doi: 10.4251/wjgo.124550
Size-dependent transcriptomic heterogeneity and microbial dysbiosis in Peutz-Jeghers syndrome colorectal polyps: An exploratory self-controlled multi-omics analysis
Meng-Xue Chen, Qian-Wen Ge, Xiang-Yu Li, Wei-Jie Dai, Hong-Gang Wang
Meng-Xue Chen, Qian-Wen Ge, Xiang-Yu Li, Wei-Jie Dai, Hong-Gang Wang, Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China
Author contributions: Chen MX and Ge QW designed and coordinated the study; Chen MX and Li XY performed the experiments, acquired and analyzed the data; Dai WJ contributed to bioinformatics analysis; Wang HG supervised the study and revised the manuscript; and all authors interpreted the data and approved the final version.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by the Jiangsu Provincial Medical Key Discipline Cultivation Unit, No. JSDW202233.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Huai'an First People’s Hospital (No. KY-2026-029-01).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw RNA-sequencing and 16S rRNA sequencing data generated in this study are available from the corresponding author at jgzwhg@njmu.edu.cn upon reasonable request. No other additional data are available.
Corresponding author: Hong-Gang Wang, Department of Gastroenterology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, No. 1 West Huanghe Road, Huaiyin District, Huai'an 223300, Jiangsu Province, China. jgzwhg@njmu.edu.cn
Received: June 18, 2026 Revised: July 11, 2026 Accepted: October 29, 2026 Published online: December 15, 2026 Processing time: 144 Days and 23.8 Hours
Abstract
BACKGROUND
In patients with Peutz-Jeghers syndrome (PJS), larger colorectal polyps carry a higher risk of malignant transformation. However, the molecular changes that occur with lesion growth remain poorly understood.
AIM
To investigate the transcriptomic and microbial differences in polyps of varying size and normal tissues from a single PJS patient.
METHODS
We performed RNA sequencing on three representative polyps of different sizes (small, medium, and large) and three matched normal mucosal tissue samples. For microbiome profiling, we conducted 16S rRNA gene sequencing on the five available polyps and the same three normal tissue samples. We then examined host-microbiome interactions through differential gene expression, functional enrichment, and multi-omics correlation network analyses.
RESULTS
In this patient, transcriptional dysregulation intensified with increasing polyp size. All polyps shared 107 core differentially expressed genes, with disrupted cell adhesion and metabolic reprogramming. Large polyps displayed a complex expression pattern with downregulation of most genes (719 downregulated vs 145 upregulated) but selective enrichment of specific immune-inflammatory pathways, including the nuclear factor kappa B, B-cell receptor, and immunoglobulin A-mediated pathways. The microbiota profiles of small and medium polyps were similar, whereas those of large polyps were distinct.
CONCLUSION
Our preliminary data reveal size-dependent heterogeneity among polyps in a patient with PJS. Small lesions displayed metabolic shifts, while large polyps showed transcriptional repression, immune activation, and dysbiosis. Further validation in a cohort of PJS patients is needed.
Core Tip: Although colorectal polyps in patients with Peutz-Jeghers syndrome are classically regarded as hamartomas, their malignant potential increases with size. Using a self-controlled, multi-omics design to analyze polyps from a single patient, we provide preliminary evidence that small and medium polyps are chiefly metabolic. However, large polyps display widespread transcriptional downregulation coupled with selective enrichment of the nuclear factor kappa B and B-cell receptor pathways, accompanied by distinct microbial dysbiosis. These exploratory findings offer molecular insight for future investigations.
