Research Paper Volume 11, Issue 19 pp 8587—8603
A molecular sub-cluster of colon cancer cells with low VDR expression is sensitive to chemotherapy, BRAF inhibitors and PI3K-mTOR inhibitors treatment
- 1 Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, FuZhou, FuJian 350001, China
- 2 Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health and Family Planning Commission, FuZhou, FuJian 350001, China
- 3 State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
Received: June 4, 2019 Accepted: September 27, 2019 Published: October 9, 2019https://doi.org/10.18632/aging.102349
How to Cite
Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Gene expression based consensus molecular subtypes (CMS) and non-negative matrix factorization (NMF) sub-clusters are robust colon cancer classification systems. Although, the molecular features are clear, colon cancer subgroups based interventions are limited. To address this problem, we analyze the CMS and NMF subgroup guided drug sensitivity in colon cancer cell lines. CMS3 subtype cells are sensitive to 5-Fluorouracil, while, CMS4 subtype cells are sensitive to cisplatin treatment. In NMF classification, a sub-cluster is specifically sensitive to chemotherapy, BRAF inhibitors, PI3K-mTOR inhibitors and NOTCH inhibitor treatment. This sub-cluster has low frequency of TP53, POLE, PIK3CA and BRAF mutation. Transcriptional analysis demonstrates low NOTCH signaling activity, low CDX2 and VDR expression in this sub-cluster. CDX2 and VDR are significantly associated with the sensitivity of chemotherapy, BRAF inhibitors and PI3K-mTOR inhibitors. Moreover, a positive correlation between VDR and CDX2 is identified. VDR and CDX2 mediated regulatory networks are constructed. At last, three or four sub-clusters classification is validated in colon cancer patients. Overall, our results suggest a molecular sub-cluster of colon cancer cells with low CDX2 and VDR expression is sensitive to chemotherapy, BRAF inhibitors and PI3K-mTOR inhibitors treatment and provide an example of translation of cancer classification to subgroup guided therapies.