While BRAF- and KRAS-mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS-mutation(+) CRC, including association with DNA methylation, remain unclear.
Two unsupervised cluster analyses revealed that CRCs form three distinct DNA methylation subsets, which are referred to as the high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME, respectively).A recent study by Yagi et al. found a fairly sensitive and specific identification of HME, IME, and LME using two marker panels analyzed by MALDI-TOF mass spectrometry (MassARRAY).
Overexpression of matrix metalloproteinase (MMP)-1, -3, -7, -9, and plasminogen activator inhibitor-1 (PAI-1) are implicated in the invasion and metastasis of colorectal cancer, while MMP-12 provides a protective role against colorectal cancer.
These findings demonstrate that the HME gene plays an important role in the inhibition of tumor progression in patients with colorectal carcinoma and that its overexpression is correlated closely with a better prognosis.