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Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer

Authors Mao Y, Feng Q, Zheng P, Yang L, Liu T, Xu Y, Zhu D, Chang W, Ji M, Ren L, Wei Y, He G, Xu J

Received 22 April 2018

Accepted for publication 28 June 2018

Published 17 September 2018 Volume 2018:10 Pages 3569—3577

DOI https://doi.org/10.2147/CMAR.S171855

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yihao Mao,1,* Qingyang Feng,1,2,* Peng Zheng,1,* Liangliang Yang,1,* Tianyu Liu,1 Yuqiu Xu,1 Dexiang Zhu,1,2 Wenju Chang,1,2 Meiling Ji,1,2 Li Ren,1,2 Ye Wei,1,2 Guodong He,1,2 Jianmin Xu1,2

1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, China; 2Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai 200030, China

*These authors contributed equally to this work

Purpose: Tumor purity is defined as the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile, and microenvironment has not been thoroughly accessed.
Materials and methods: Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA, were retrospectively collected (n=1,248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Survival-related analyses were performed on microarray dataset containing GSE17536/17537 and GSE39582 (n=794), whereas TCGA dataset was utilized for subsequent genomic analysis (n=454).
Results: Right-sided CC patients showed a significantly lower tumor purity. Low purity CC conferred worse survival, and tumor purity was identified as an independent prognostic factor. Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity, with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Lymphocyte-activation gene 3 [LAG-3] and T-cell immunoglobulin and mucin-domain containing-3 [TIM-3]) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumor purity.
Conclusion: Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.

Keywords: adjuvant chemotherapy, colon cancer, prognosis, tumor microenvironment, tumor purity

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