Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation.
Bottom Line: Methylation of the retinoic acid receptor β gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1-2 versus 33·9 per cent for T3-4, P < 0·001; CHFR: 5·5 per cent for T1-2 versus 12·6 per cent for T3-4, P = 0·005).Gene methylation associated with nodal metastasis included RARB (47·1 per cent for N- versus 31·7 per cent for N+; P = 0·008), chemokine ligand 12, CXCL12 (12·3 per cent for N- versus 8·9 per cent for N+; P = 0·021), and death-associated protein kinase 1, DAPK1 (19·3 per cent for N- versus 12·3 per cent for N+; P = 0·022).RARB methylation was also associated with LVI (45·1 per cent for LVI- versus 31·7 per cent for LVI+; P = 0·038).
Affiliation: School of Cancer Sciences, Vincent Drive, University of Birmingham, Birmingham, B15 2TT, UK.Show MeSH
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Mentions: Clinical and pathological data are summarized in Table 1. Gene-specific hypermethylation was observed in rectal cancer, compared with matched adjacent normal mucosa (Figs 1 and 2; Fig. S1, supporting information). As expected, the methylation level of LINE-1, a marker of global methylation, was lower in rectal cancer (Fig. 2). Median percentage methylation was calculated for each of 15 genes for analysis of association with tumour stage and pathology variables (Figs 6). Early-stage (pathological tumour (pT) 1–2) and node-negative tumours had higher median percentage methylation for RARB (Figs 3 and 4). Larger tumours (median diameter 40 mm or more) had higher methylation levels of checkpoint with forkhead and ring finger gene, CHFR (Fig. 6), as did more advanced lesions (pT3–4). Node-negative tumours also exhibited increased methylation levels of chemokine ligand 12 gene (CXCL12) and death-associated protein kinase 1 gene (DAPK1) compared with node-positive tumours (Fig. 4). Tumours with either LVI or distant metastasis were associated with lower methylation values of RARB (Figs 5 and 6). In addition, tumours with organ secondaries were associated with less methylation of cadherin 13 gene, CDH13, and CXCL12 (Fig. 5).
Affiliation: School of Cancer Sciences, Vincent Drive, University of Birmingham, Birmingham, B15 2TT, UK.