Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer

Abstract

Background DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC. Methods A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis. Results Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140–3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better. Conclusions RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.

Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis

“…The optimal cut-off points for each marker in each prognostic analysis were determined using a method based on maximally selected rank statistics. 18 Additionally, for validated methylation biomarkers, two sensitivity analyses were performed by using the median as cut-off values or standardized continuous variables, and then repeated the multivariable Cox regression analyses.…”

Loss ofUBE3Aimpacts both neuronal and non-neuronal cells in human cerebral organoids

“…(E) Heatmap of top differentially expressed markers between EN-CL and non EN-CL neurons (EN, IN, Neuron, Neuron/IP, Neuron-HSP). Differentially expressed markers were grouped by cellular function: synapse-related ( SLC24A2 89–92 , LRRC7 93 , ANKS1B 94 , PLXND1 95 , SLC4A10 96 , LRRTM4 97 , KCNQ5 98 , GRIA3 90–92,99 , GRIA1 100 , DLGAP1 101 , CACNA1E 90–92,102 , ABHD6 103,104 , RIMS2 105–108 , LIN7A 109 , EPHA5 110,111 , SDK1 90–92,112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 90–92,117,118 , DAB1 119–121 , NBEA 90–92,122,123 ), axon/dendrite development ( LIN7A 109 , EPHA5 110,111 , SDK1 90–92,112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 90–92,117,118 , NELL2 124 , NFIB 125 , MYO5B 126 , ARPP21 127 , EPHA7 128,129 , NEO1 130 , SHTN1 131–133 , SRGAP1 134 , SOX5 135 , DAB1 119–121 ), cell migration/cortical layering ( LIN7A 109 , FLRT2 90–92,117,118 , NEO1 130 , SHTN1 131–133 , SRGAP1 134 , SOX5 135 , DAB1 119–121 , AFF3 136 , BCL11A 137 , ZBTB18 138,139…”

“…[89][90][91][92] , LRRC7 93 , ANKS1B 94 , PLXND195 , SLC4A1096 , LRRTM4 97 , KCNQ598 , GRIA3 90-92,99 , GRIA1 100 , DLGAP1 101 , CACNA1E 90-92,102 , ABHD6103,104 , RIMS2[105][106][107][108] , LIN7A 109 , EPHA5…”

Loss of ARHGAP40 expression in basal cell carcinoma via CpG island hypermethylation

“…Assessing RIMS2 methylation and KRAS status could predict the prognosis of colorectal cancer patients. 11 BCCs grow slowly, are locally invasive, rarely metastasize and are not fatal; thus, BCC has a good prognosis. To the best of our knowledge, epigenetic alterations have not been investigated in depth in BCC.…”