Hotspot KRAS exon 2 mutations in CD166 positive colorectal cancer and colorectal adenoma cells

Hung Lai Wong, Lawrence Po Wah Ng, Su Pin Koh, Lawrence Wing Chi Chan, Evelyn Yin Kwan Wong, Vivian Weiwen Xue, Hin Fung Andy Tsang, Amanda Kit Ching Chan, Ka Yue Chiu, Wah Cheuk, Sze Chuen Cesar Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)20426-20438
Number of pages13
JournalOncotarget
Volume9
Issue number29
DOIs
Publication statusPublished - 17 Apr 2018

Keywords

  • CD166
  • Colorectal adenoma
  • Colorectal cancer
  • Immunohistochemical staining
  • KRAS exon 2 mutations

ASJC Scopus subject areas

  • Oncology

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