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Poster display session

16P - KRAS and CTLA-4 expression profiling in circulating tumor cells in patients with colorectal cancers

Date

15 Oct 2022

Session

Poster display session

Presenters

Sharmin Aktar

Citation

Annals of Oncology (2022) 33 (suppl_8): S1383-S1430. 10.1016/annonc/annonc1095

Authors

S. Aktar1, T. Cheng1, S. Gamage2, F. Islam3, V. Gopalan1, A.K. Lam1

Author affiliations

  • 1 Griffith University, Gold Coast, Gold Coast/AU
  • 2 Bond University, Gold Coast/AU
  • 3 University of Rajshahi, Rajshahi/BD
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Abstract 16P

Background

Circulating tumour cells (CTCs) could escape the host immune surveillance by altering the expression of immune regulatory molecules (PD-L1, PD-L2, CTLA-4, CD47) in cancer patients. Recent studies suggested that KRAS mutation might promote the immune escape of tumour cells by inducing the upregulation of these molecules. However, the regulatory effects of KRAS on the expression of CTLA-4 in patients with colorectal cancer (CRC) have yet to be explored. This study aimed to investigate KRAS and CTLA-4 mRNA expression profiling in CTCs from patients with CRC.

Methods

Peripheral blood from 50 CRC patients was collected to isolate CTCs using a negative selection (EasySepTM) method. The presence of CTCs was confirmed by immunofluorescence staining using multiple tumor cell surface biomarkers (EpCAM, SNAIL-1, E-cadherin and MMP-9). The mRNA expressions of CTLA-4 and KRAS in CTCs were analysed by RT-qPCR. The association between the presence of CTCs and clinicopathological variables was evaluated.

Results

The cells, which are positive for at least one of the markers (EPCAM, SNAIL-1, E-Cadherin and MMP-9), and enlarged nucleus and cell size >8μm were considered as CTCs. Approximately 66% (n=33/50) of patients with CRC were CTC positive. The majority of patients with zero CTC or low CTC counts (˂10 CTCs) were diagnosed with early stages (stage I or II), while patients with higher CTCs counts (≥10 CTCs) were with advanced stages (stages III or IV) with CRC ((p < 0.0064). The presence of CTC were also significantly correlated with tumour type, size. The expressions of CTLA-4 and KRAS were higher in CTC positive groups compared to CTC negative in patients with CRC. Also, the expression levels of these two molecules were positively correlated to each other (Spearman’s rank test, r = 0. 0.6674; p<0.0001). Additionally, from clinical data analysis, we found that CTLA-4 gene expression weakly correlates with KRAS mutation (p < 0.060).

Conclusions

Our study demonstrated that KRAS gene activation might upregulate CTLA-4 expression in patients with CRC. Thus, understanding the role of the interactions between oncogenes and immune checkpoint molecules is essential to fully uncover the molecular mechanisms involved in immune escape by CTCs in patients with CRC.

Legal entity responsible for the study

The authors.

Funding

School of Medicine and Dentistry, Griffith University.

Disclosure

All authors have declared no conflicts of interest.

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