英國研究人員周三表示，嚴(yán)重惡性癌癥患者可以通過檢測干細(xì)胞標(biāo)記蛋白——核纖層蛋白A來及早確認(rèn),。這意味著一種更精確定位惡性腸癌的新方法問世,，改進(jìn)病人存活率的定制療法成為可能。
目前正在研發(fā)中的新測試手段可以幫助醫(yī)生確定如何以及何時(shí)治療不同類型的癌癥,，這一發(fā)現(xiàn)就是最新的一個(gè)例子,。
在腸癌四階段的最早兩個(gè)階段，病人往往進(jìn)行手術(shù)切除腫瘤,，但是很少進(jìn)行化療，因?yàn)檫@種毒性療法可能引起很大傷害,。
盡管如此,，新的研究顯示大約1/3的早期病人擁有核纖層蛋白A干細(xì)胞標(biāo)記,，這表示他們得的是一種更嚴(yán)重的癌癥，因此進(jìn)行化療對他們很可能大有好處,。該研究小組得出結(jié)論指,，核纖層蛋白A檢測呈陽性的病人在手術(shù)之外還應(yīng)該進(jìn)行化療，以便增加他們的存活率,。
達(dá)拉謨大學(xué)(Durham University)和東北英格蘭干細(xì)胞研究所如今準(zhǔn)備開發(fā)一種功能強(qiáng)大的檢測工具，該工具最終可能廣泛用于醫(yī)院中,。
他們的研究發(fā)表在《公共科學(xué)圖書館·綜合》上,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 3(8): e2988. doi:10.1371/journal.pone.0002988 Willis ND, Cox TR, Rahman-Casañs SF, Smits K, Przyborski SA, et al. (2008) Lamin A/C Is a Risk Biomarker in Colorectal Cancer.
Lamin A/C Is a Risk Biomarker in Colorectal Cancer
Naomi D. Willis1, Thomas R. Cox1, Syed F. Rahman-Casañs2, Kim Smits3, Stefan A. Przyborski1, Piet van den Brandt3, Manon van Engeland4, Matty Weijenberg3, Robert G. Wilson2, Adriaan de Bruïne4, Christopher J. Hutchison1*
Background
A-type lamins are type V intermediate filament proteins encoded by the gene LMNA. Mutations in LMNA give rise to diverse degenerative diseases related to premature ageing. A-type lamins also influence the activity of the Retinoblastoma protein (pRb) and oncogenes such a β-catenin. Consequently, it has been speculated that expression of A-type lamins may also influence tumour progression.
Methodology/Principal Findings
An archive of colorectal cancer (CRC) and normal colon tissue was screened for expression of A-type lamins. We used the Cox proportional hazard ratio (HR) method to investigate patient survival. Using CRC cell lines we investigated the effects of lamin A expression on other genes by RT-PCR; on cell growth by FACS analysis; and on invasiveness by cell migration assays and siRNA knockdown of targeted genes. We found that lamin A is expressed in colonic stem cells and that patients with A-type lamin-expressing tumours have significantly worse prognosis than patients with A-type lamin negative tumours (HR = 1.85, p = 0.005). To understand this finding, we established a model system based upon expression of GFP-lamin A in CRC cells. We found that expression of GFP-lamin A in these cells did not affect cell proliferation but did promote greatly increased cell motility and invasiveness. The reason for this increased invasiveness was that expression of lamin A promoted up-regulation of the actin bundling protein T-plastin, leading to down regulation of the cell adhesion molecule E-cadherin.
Conclusions
Expression of A-type lamins increases the risk of death from CRC because its presence gives rise to increased invasiveness and potentially a more stem cell-like phenotype. This report directly links A-type lamin expression to tumour progression and raises the profile of LMNA from one implicated in multiple but rare genetic conditions to a gene involved in one of the commonest diseases in the Western World.
