Correlation between KRAS Mutation and CTLA-4 mRNA Expression in Circulating Tumour Cells: Clinical Implications in Colorectal Cancer.

Combination strategies of inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of in CTCs and matched CRC tissues and compared mRNA expression of and between wild-type and -mutated CTCs and CRC tissues. Clinicopathological correlations were also compared. Six known mutations of were identified at both codon 12 and codon 13 (c.35G>T/G12V, c.35G>A7/G12D, c.35G>C/G12A, c.34G>A/G12S, c.38G>C/G13A, and c.38G>A/G13D). Three CTC samples harboured the identified mutations (16.7%; 3/18), while fifteen matched primary tumour tissues (65.2%, 15/23) showed the mutations. CTCs harbouring the variant were different from matched CRC tissue. All the mutations were heterozygous. Though insignificant, mRNA expression was higher in patients carrying mutations. Patients harbouring mutations in CTCs were more likely to have poorly differentiated tumours ( = 0.039) and with lymph node metastasis ( = 0.027) and perineural invasion ( = 0.014). mutations in CTCs were also significantly correlated with overall pathological stages ( = 0.027). These findings imply the genetic basis of with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient's disease.