Associations between colorectal cancer molecular markers and pathways with clinicopathologic features in older women.
Associations between colorectal cancer molecular markers and pathways with clinicopathologic features in older women.
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DOI：
10.1053/j.gastro.2013.05.001
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发表时间：
2013-08
期刊：
影响因子：
29.4
通讯作者：
Limburg PJ
中科院分区：
文献类型：
--
作者：
Samadder NJ;Vierkant RA;Tillmans LS;Wang AH;Weisenberger DJ;Laird PW;Lynch CF;Anderson KE;French AJ;Haile RW;Potter JD;Slager SL;Smyrk TC;Thibodeau SN;Cerhan JR;Limburg PJ
结直肠肿瘤具有很大程度的分子异质性。基于微卫星不稳定性（MSI）、CpG岛甲基化表型（CIMP）以及BRAF和KRAS突变的特定组合，提出了三种综合致癌途径（即传统、交替和锯齿状）。我们使用了基于人群的爱荷华州妇女健康研究（n = 41，836）的资源，将结直肠肿瘤的标志物、整合途径、临床和病理学特征（包括生存时间）联系起来。我们评估了来自732例新发结直肠肿瘤的存档标本，并将其表征为微卫星稳定（MSS）、MSI高或MSI低、CIMP高或CIMP低、CIMP阴性以及BRAF和/或KRAS突变阳性或阴性。从563个肿瘤（77%）中收集了信息性标志物数据，这些肿瘤被分配到以下整合途径：传统的（MSS、CIMP阴性、BRAF突变阴性和KRAS突变阴性; n = 170），交替（MSS，CIMP低，BRAF突变阴性，KRAS突变阳性; n = 58），锯齿状（任何MSI、CIMP高、BRAF突变阳性和KRAS突变阴性; n = 142）或未分配（n = 193）。采用多变量校正的考克斯比例风险回归模型评估相关性。患者的平均年龄（P = 0.03）和肿瘤的解剖亚部位（P = 0.0001）和分级（P = 0.0001）与综合路径分配显著相关。结直肠癌（CRC）死亡率与传统、替代或锯齿状途径无关，但与一部分未分配途径的肿瘤（MSS或MSI低、CIMP阴性、BRAF突变阴性和KRAS突变阳性）相关（与传统途径相比，n = 96例;相对风险= 1.76; 95%置信区间为1.07-2.89）。我们确定了与分子定义的CRC亚型相关的临床和病理学特征。然而，需要更多的研究来确定这些特征如何影响预后。
Colorectal tumors have a large degree of molecular heterogeneity. Three integrated pathways of carcinogenesis (ie, traditional, alternate, and serrated) have been proposed, based on specific combinations of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in BRAF and KRAS. We used resources from the population-based Iowa Women’s Health Study (n = 41,836) to associate markers of colorectal tumors, integrated pathways, and clinical and pathology characteristics, including survival times. We assessed archived specimens from 732 incident colorectal tumors and characterized them as microsatellite stable (MSS), MSI high or MSI low, CIMP high or CIMP low, CIMP negative, and positive or negative for BRAF and/or KRAS mutations. Informative marker data were collected from 563 tumors (77%), which were assigned to the following integrated pathways: traditional (MSS, CIMP negative, BRAF mutation negative, and KRAS mutation negative; n = 170), alternate (MSS, CIMP low, BRAF mutation negative, and KRAS mutation positive; n = 58), serrated (any MSI, CIMP high, BRAF mutation positive, and KRAS mutation negative; n = 142), or unassigned (n = 193). Multivariable-adjusted Cox proportional hazards regression models were used to assess the associations of interest. Patients’ mean age (P = .03) and tumors’ anatomic subsite (P = .0001) and grade (P = .0001) were significantly associated with integrated pathway assignment. Colorectal cancer (CRC) mortality was not associated with the traditional, alternate, or serrated pathways, but was associated with a subset of pathway-unassigned tumors (MSS or MSI low, CIMP negative, BRAF mutation negative, and KRAS mutation positive) (n = 96 cases; relative risk = 1.76; 95% confidence interval, 1.07–2.89, compared with the traditional pathway). We identified clinical and pathology features associated with molecularly defined CRC subtypes. However, additional studies are needed to determine how these features might influence prognosis.
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影响因子：
3.8
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
通讯作者：
Soong R
影响因子：
3.9
作者：
Kalady, Matthew F.;DeJulius, Kathryn L.;Church, James M.
通讯作者：
Church, James M.
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
5
作者：
FOLSOM, AR;KAYE, SA;WALLACE, RB
通讯作者：
WALLACE, RB
影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.