DNA Methylation Module Network-Based Prognosis and Molecular Typing of Cancer.

ABSTRACT

Achieving cancer prognosis and molecular typing is critical for cancer treatment. Previous studies have identified some gene signatures for the prognosis and typing of cancer based on gene expression data. Some studies have shown that DNA methylation is associated with cancer development, progression, and metastasis. In addition, DNA methylation data are more stable than gene expression data in cancer prognosis. Therefore, in this work, we focused on DNA methylation data. Some prior researches have shown that gene modules are more reliable in cancer prognosis than are gene signatures and that gene modules are not isolated. However, few studies have considered cross-talk among the gene modules, which may allow some important gene modules for cancer to be overlooked. Therefore, we constructed a gene co-methylation network based on the DNA methylation data of cancer patients, and detected the gene modules in the co-methylation network. Then, by permutation testing, cross-talk between every two modules was identified; thus, the module network was generated. Next, the core gene modules in the module network of cancer were identified using the K-shell method, and these core gene modules were used as features to study the prognosis and molecular typing of cancer. Our method was applied in three types of cancer (breast invasive carcinoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma). Based on the core gene modules identified by the constructed DNA methylation module networks, we can distinguish not only the prognosis of cancer patients but also use them for molecular typing of cancer. These results indicated that our method has important application value for the diagnosis of cancer and may reveal potential carcinogenic mechanisms.