Microenvironment of Adjacent Non-Neoplastic Regions Determines Prognostic Outcomes in Locally Advanced Colorectal Cancer after Surgical Resection: A Multi-Center & Multi-Omics study

Woong-Yang Park, Yeong Hak Bang, Ji Hye Choi, Kyunghee Park, Jinyeong Lim, Boram Lee, Kyung Yeon Han, Dae Hee Pyo, Yong Beom Cho, Tae-You Kim, Kyu Joo Park, Seung-Bum Ryoo, Sung-Bum Kang, Chang Sik Yu, Jaeim Lee, Kil-yong Lee, Kyu-Tae Kim, Jin-Young Lee, Young-Joon Kim
2023 · doi:10.21203/rs.3.rs-3375190/v1
preprint OA: closed CC-BY-4.0
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Abstract

Abstract We aimed to predict postoperative prognosis of stage II/III colorectal cancer (CRC). Tumor-like normal microenvironment (tNME) and healthy normal microenvironment (hNME) groups were created using RNA sequencing (RNA-seq) data derived from 273 tumors and 273 paired normal tissues from margins of resected specimens. With a median follow-up of 58.2 months, the tNME group showed poor 5-year recurrence-free survival (54.7 vs. 73.0%, HR = 1.94, P = 0.002) and 5-year overall survival (78.2 vs. 83.0%, HR = 1.76, P = 0.033). Only the tNME group showed similar microbiome diversity between tumor and normal tissues. scRNA-seq revealed a positive co-occurrence of Th17, GZMKhighCD8+T cells, and IL1Bhigh neutrophils in the tumor and normal tissues of tNME. A high proportion of EMP1high epithelial cells was observed in the tNME group, with upregulated epithelial-mesenchymal transition and leukocyte signaling pathways. In conclusion, the microenvironmental status of normal tissues offers a promising biomarker for stage II/III CRC.

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License: CC-BY-4.0