Molecular profiling of colon tumors: the search for clinically relevant biomarkers of progression, prognosis, therapeutics, and predisposition.
Molecular profiling of colon tumors: the search for clinically relevant biomarkers of progression, prognosis, therapeutics, and predisposition.
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DOI：
10.1245/s10434-011-1615-5
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发表时间：
2011-12
影响因子：
3.7
通讯作者：
Barany F
中科院分区：
文献类型：
--
作者：
Bacolod MD;Barany F
如果适当地转化为临床应用，我们关于生物标志物的知识可能会导致更有效的方法来对抗结直肠癌（CRC）。生物标志物是指示疾病进展、易感性、预后或治疗选择的生物分子、遗传或细胞遗传学属性。对于CRC，这些包括染色体不稳定性，KRAS和TP53突变，18q丢失和癌胚抗原（CEA）水平升高，这些都与不良预后相关。18q丢失的预后意义可以归因于SMAD4或DCC表达的减少，尽管染色体臂实际上大量存在下调与更差生存相关的基因。潜在地，预后生物标志物的鉴定可以帮助肿瘤学家决定手术后是否需要辅助化疗。如果正在考虑靶向治疗，则可能需要检测治疗性生物标志物。识别高渗透性易感性标志物（如APC和MLH1突变）可以挽救携带者的生命，他们将不得不在更早的年龄接受结肠镜检查。根据最近的研究，即使是散发的CRCs也可能有一些遗传成分。全基因组关联研究（使用SNP阵列）表明，某些基因的多态性可能对CRC易感性有微妙的影响。我们自己的基于SNP阵列的分析表明，长时间的生殖系纯合性（同源性），表明血缘关系，也可能是CRC易感性的因素。
If properly translated to clinical use, our knowledge about biomarkers may lead to a more effective way of combating colorectal cancer (CRC). Biomarkers are biomolecular, genetic, or cytogenetic attributes indicative of the disease’s progression, predisposition, prognosis, or therapeutic options. For CRC, these include chromosomal instability, mutations in KRAS and TP53, loss of 18q, and elevated level of carcinoembryonic antigen (CEA), which are all associated with poor prognosis. The prognostic significance of 18q loss can be attributed to reduced expression of SMAD4, or DCC, although the chromosomal arm is actually heavily populated by genes whose downregulation correlate to worse survival. Potentially, identification of prognostic biomarkers can help the oncologist decide whether adjuvant chemotherapy is necessary after surgery. Testing for therapeutic biomarkers can be necessary if targeted therapeutics are being considered. The identification of highly penetrant predisposition markers (such as mutations in APC and MLH1) can be a lifesaver for carrier individuals, who would then have to undergo colonoscopy at an earlier age. Even sporadic CRCs may have some hereditary components, according to recent studies. Genome-wide association studies (using SNP arrays) showed that polymorphisms of certain genes can have subtle influence on CRC predisposition. Our own SNP array-based analysis suggested that long stretches of germline homozygosity (autozygosity), indicative of consanguinity, may also factor in CRC predisposition.
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影响因子：
11.2
作者：
Bacolod MD;Schemmann GS;Giardina SF;Paty P;Notterman DA;Barany F
通讯作者：
Barany F
影响因子：
3
作者：
Kim, Seung Tae;Lee, Jeeyun;Park, Young Suk
通讯作者：
Park, Young Suk
影响因子：
4.7
作者：
Andersen, Claus Lindbjerg;Wiuf, Carsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
7.5
作者：
Al-Mulla, F;Behbehani, AI;Going, JJ
通讯作者：
Going, JJ
影响因子：
168.9
作者：
Gray, Richard;Barnwell, Jennifer;Kerr, David J.
通讯作者：
Kerr, David J.