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http://hdl.handle.net/10397/78219
Title: | Hotspot KRAS exon 2 mutations in CD166 positive colorectal cancer and colorectal adenoma cells | Authors: | Wong, HL Ng, LPW Koh, SP Chan, LWC Wong, EYK Xue, VW Tsang, HFA Chan, AKC Chiu, KY Cheuk, W Wong, SCC |
Issue Date: | 2018 | Source: | Oncotarget, 2018, v. 9, no. 29, p. 20426-20438 | Abstract: | Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Recent studies have shown that cancer stem cells (CSCs) are an important cause of tumor recurrence and metastasis. We hypothesized that CSCs marker CD166-positive CRC and colorectal adenoma (CAD) cells consist of more hotspot mutations than CD166-negative CRC and colorectal adenoma cells. To verify this, formalin fixed paraffin embedded tissue specimens from 42 patients each with CRC and CAD were recruited and CD166 immunohistochemical (IHC) staining followed by macrodissection was performed. DNA extracted was used for quantitative polymerase chain reaction detection on a somatic mutation array. Results showed that the immunoreactivity of CD166 protein had significant difference among CRC, CAD, and normal colorectal epithelial tissues (NCET) (P < 0.0001, Kruskal-Wallis test). Moreover, nucleotide changes were found in APC, KRAS, P53, PIK3CA, FBXW7 and SRC genes. Among those genes, KRAS exon 2 mutations were validated in another cohort of 70 CRC and 72 CAD specimens. Results showed that the difference in percentage of KRAS exon 2 mutations between CD166 positive and CD166 negative CRC specimens was significant (P < 0.05, chi-square test). Long term follow-up of the CRC patients showed that CD166-positive KRAS exon 2 mutations was useful in discriminating CRC patients with worse outcome. This study has provided evidence that KRAS exon 2 mutations are concentrated in CD166-positive cancer cells, with prognostic significance in CRC, and those mutations are also detected in CAD. | Keywords: | CD166 Colorectal adenoma Colorectal cancer Immunohistochemical staining KRAS exon 2 mutations |
Publisher: | Impact Journals LLC | Journal: | Oncotarget | ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.24921 | Rights: | Copyright: Wong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The following publication Wong, H. L., Ng, L. P. W., Koh, S. P., Chan, L. W. C., Wong, E. Y. K., Xue, V. W., ... & Wong, S. C. C. (2018). Hotspot KRAS exon 2 mutations in CD166 positive colorectal cancer and colorectal adenoma cells. Oncotarget, 9(29), 20426-20438 is available at https://doi.org/10.18632/oncotarget.24921 |
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