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Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation
Oleh:
Leong, K.J.
;
Beggs, A.
;
James, J.
;
Morton, D.G.
Jenis:
Article from Article - diterbitkan di jurnal ilmiah internasional
Dalam koleksi:
BJS: British Journal of Surgery vol. 101 no. 10 (Sep. 2014)
,
page 1299-1309.
Topik:
rectal cancer
;
rectum
;
tumor
;
endoscopic microsurgery
;
colorectal cancer
;
kanker usus besar
;
rectal tumour
Ketersediaan
Perpustakaan FK
Nomor Panggil:
B15.K
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
Background Total mesorectal excision (TME) remains commonplace for T1–2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated. Methods Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model. Results Methylation of the retinoic acid receptor ß 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). Predictive models for nodal metastasis and LVI achieved sensitivities of 91·1 and 85·0 per cent, and specificities of 55·3 and 45·3 per cent, respectively. Conclusion This methylation biomarker panel provides a step towards accurate discrimination of indolent and aggressive rectal cancer subtypes. This could offer an improvement over the current standard of care, whereby fit patients are offered radical surgery.
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