Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation.
Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation.
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DOI：
10.1016/j.tranon.2016.06.002
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发表时间：
2016-08
影响因子：
5
通讯作者：
Boardman LA
中科院分区：
文献类型：
--
作者：
Druliner BR;Rashtak S;Ruan X;Bae T;Vasmatzis N;O'Brien D;Johnson R;Felmlee-Devine D;Washechek-Aletto J;Basu N;Liu H;Smyrk T;Abyzov A;Boardman LA
大多数结直肠癌(CRC)起源于腺瘤性息肉。在这项研究中，我们试图将未被认识的起源于残留息肉的结直肠癌(CRC RPO+)作为一个实体，作为研究结直肠癌发生的模型。我们确定了所有在明尼苏达州罗切斯特市梅奥诊所接受10年以上评估的经活检证实为CRRPO+的受试者，并将他们的临床和病理特征与无残留息肉的结直肠癌(CRCRRPO)进行了比较(CRRPO和−)。调整了年龄、分期和分级后，总体生存率和无病生存率与CRRPO+和RPO+−病例之间的等效风险比重叠。通过全基因组测序获得的体细胞基因组图谱和RNA-SEQ技术获得的CRRPO+肿瘤的基因表达谱与癌症基因组图谱评估的年龄和性别匹配的CRRRPO-−进行比较。与CRRPO和−相比，CRRPO+病例更容易发现病情较轻、早期的病例。然而，在相同的疾病分期和分级下，他们的临床病程与CRRPO和−非常相似。结直肠癌中常见突变基因的突变频率在结直肠癌Rpo+和−病例中相似。同样，基因表达模式在Rpo+和−病例中无法区分。我们已经证实，CRRPO+在临床和生物学上与CRCRRPO和−相似，可以作为腺瘤向肿瘤转化的模型。
The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO +) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO + that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO −). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO + and RPO − cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO + tumors were compared with that of age -and gender-matched CRC RPO − evaluated by The Cancer Genome Atlas. CRC RPO + cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO −. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO −. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO + and RPO − cases. Likewise, gene expression patterns are indistinguishable between the RPO + and RPO − cases. We have confirmed that CRC RPO + is clinically and biologically similar to CRC RPO − and may be utilized as a model of the adenoma to carcinoma transition.