Innovative molecular subtypes of multiple signaling pathways in colon cancer and validation of FMOD as a prognostic-related marker

结肠癌中多种信号通路的创新分子亚型以及 FMOD 作为预后相关标志物的验证

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作者:Zhujiang Dai #, Xiang Peng #, Xuewei Cui #, Yuegui Guo, Jie Zhang, Xia Shen, Chen-Ying Liu, Yun Liu

Conclusion

The identification of molecular subtypes could provide innovative ideas for immunotherapy of colon cancer.

Methods

According to the enrichment of four dimensions, we performed consensus cluster analysis and identified three robust molecular subtypes for colon cancer, namely immune enriched, immune deficiency, and stroma enriched. We characterized and validated the immune infiltration, gene mutations, copy number variants, methylation, protein expression, and clinical features in different datasets. Finally, we developed an 8-gene risk prognostic model and proposed the innovative RiskScore. In addition, a nomogram model was constructed combining clinical characteristics and RiskScore to validate its excellent clinical predictive power.

Purpose

Colon cancer is highly heterogeneous in terms of the immune and stromal microenvironment, genomic integrity, and oncogenic properties; therefore, molecular subtypes of the four characteristic dimensions are expected to provide novel clues for immunotherapy of colon cancer.

Results

Combining clinical patient tissue samples and histochemical microarray data, we found that high FMOD expression in tumor epithelial cells was associated with poorer patient prognosis, but FMOD expression in the mesenchyme was not associated with prognosis. In pan-cancer, RiskScore, a prognostic model constructed based on characteristic pathway scores, was a poor prognostic factor for malignancy and was negatively associated with immunotherapy response.

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