來(lái)自英國(guó)劍橋大學(xué)癌癥研究中心的研究人員對(duì)90名II期腸癌患者腫瘤樣本的分析發(fā)現(xiàn)：他們可以將這些腫瘤樣品分為三個(gè)不同的亞類(lèi)型.隨后,他們開(kāi)發(fā)了一組（共146個(gè)）能夠區(qū)分這些亞類(lèi)型的基因,并進(jìn)一步對(duì)1100例患者的腫瘤樣本進(jìn)行了分析,結(jié)果證實(shí)確有三個(gè)不同的腸癌亞類(lèi)型.
其中有兩個(gè)亞類(lèi)型是已知的,但超過(guò)四分之一的患者患上一種未知的腸癌亞類(lèi)型,這種新型的腸癌以前從來(lái)沒(méi)有被單獨(dú)分出來(lái)過(guò).并且患上這種腸癌的患者的病況可能會(huì)比其他兩種更為嚴(yán)重.不僅如此,這種腫瘤的侵略性更強(qiáng)且對(duì)西妥昔單抗（Cetuximab）具有更強(qiáng)的耐受性.西妥昔單抗是由英國(guó)癌癥研究中心的科學(xué)家于20世紀(jì)80年代發(fā)現(xiàn)的一種針對(duì)EGFR的單克隆抗體,其與EGFR結(jié)合可以阻斷腫瘤細(xì)胞信號(hào)傳導(dǎo)并促進(jìn)受體內(nèi)部化及降解.
進(jìn)一步的實(shí)驗(yàn)表明,新發(fā)現(xiàn)的這種腸腫瘤亞類(lèi)型以不同于另外兩種的方式進(jìn)行擴(kuò)散,這就解釋了為什么它們具有更強(qiáng)的侵略性.基于此,研究人員迫切的需要對(duì)這種新型腫瘤做進(jìn)一步研究,以了解這個(gè)特定的腸癌亞類(lèi)型并開(kāi)發(fā)出新的治療藥物.
該項(xiàng)研究的領(lǐng)導(dǎo)者Louis Vermeulen博士說(shuō)：“我們是通過(guò)研究腫瘤樣品細(xì)胞的基因的行為發(fā)現(xiàn)這種新的腸癌亞類(lèi)型的,這種方法能使我們快速簡(jiǎn)便檢測(cè)到這種腫瘤.當(dāng)我們進(jìn)一步研究如何區(qū)分這三個(gè)亞類(lèi)型的時(shí)候,我們發(fā)現(xiàn),第三種亞類(lèi)型從癌癥的早期就開(kāi)始擴(kuò)散,而另外兩種腫瘤的擴(kuò)散發(fā)生在晚期,因此,我們推測(cè)不同亞類(lèi)型之間的差異可能源于腫瘤細(xì)胞的來(lái)源而不是特定的突變位點(diǎn).”
英國(guó)癌癥研究中心臨床研究主任Kate Law說(shuō)：“四月是腸癌的高發(fā)期,在過(guò)去的40年里,結(jié)腸癌患者的存活率翻了一番,這主要是由于我們對(duì)腸癌做了大量的研究并對(duì)這種疾病有了更深入地了解,今后,像這樣的揭示癌癥本質(zhì)的研究必不可少的,這樣我們就能采取更加個(gè)性化的方法來(lái)治療癌癥并且更早地開(kāi)發(fā)出治療癌癥的方法.”（生物谷Bioon.com）
doi:10.1038/nm.3174
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Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions
Felipe De Sousa E Melo,Xin Wang,Marnix Jansen,Evelyn Fessler,Anne Trinh,Laura P M H de Rooij,Joan H de Jong,Onno J de Boer,Ronald van Leersum,Maarten F Bijlsma,Hans Rodermond,Maartje van der Heijden,Carel J M van Noesel,Jurriaan B Tuynman,Evelien Dekker,Florian Markowetz,Jan Paul Medema& Louis Vermeulen
Colon cancer is a clinically diverse disease. This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents1. More insight into the biological diversity of colon cancers, especially in relation to clinical features, is therefore needed. We demonstrate, using an unsupervised classification strategy involving over 1,100 individuals with colon cancer, that three main molecularly distinct subtypes can be recognized. Two subtypes have been previously identified and are well characterized (chromosomal-instable and microsatellite-instable cancers)2. The third subtype is largely microsatellite stable and contains relatively more CpG island methylator phenotype–positive carcinomas but cannot be identified on the basis of characteristic mutations. We provide evidence that this subtype relates to sessile-serrated adenomas, which show highly similar gene expression profiles, including upregulation of genes involved in matrix remodeling and epithelial-mesenchymal transition. The identification of this subtype is crucial, as it has a very unfavorable prognosis and, moreover, is refractory to epidermal growth factor receptor–targeted therapy.
