Gene Expression Analysis of Immune Regulatory Genes in Circulating Tumour Cells and Peripheral Blood Mononuclear Cells in Patients with Colorectal Carcinoma

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 5051
• Main Authors: Aktar, Sharmin, Hamid, Faysal Bin, Gamage, Sujani Madhurika Kodagoda, Cheng, Tracie, Parkneshan, Nahal, Lu, Cu Tai, Islam, Farhadul, Gopalan, Vinod, Lam, Alfred King-Yin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Adenocarcinoma; Adenomatous polyposis coli; Biomarkers, Tumor - genetics; Blood circulation; c-Myc protein; Cancer; Cancer therapies; Carcinoma; circulating tumour cells; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - pathology; CTLA-4; CTLA-4 Antigen - metabolism; CTLA-4 protein; Gene expression; Gene Expression Profiling; Genes; Genes, Regulator; Genetic aspects; Health aspects; Humans; immune checkpoint molecules; immune escape mechanism; Immune system; Immunotherapy; K-Ras protein; KRAS; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Lymph nodes; Medical research; Medicine, Experimental; Metastases; Metastasis; Microenvironments; molecular characterisation; Monitoring; Myc protein; Neoplastic Cells, Circulating - pathology; p53 Protein; PD-L1 protein; Peripheral blood mononuclear cells; Photographic industry; Proto-Oncogene Proteins p21(ras) - genetics; Telemedicine; Therapeutic applications; Therapeutic targets; Tumor Microenvironment; Tumor proteins; Tumors; Australia; Japan; circulating tumour cells; CTLA-4; KRAS; immune escape mechanism; immune checkpoint molecules; molecular characterisation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24055051

Information regarding genetic alterations of driver cancer genes in circulating tumour cells (CTCs) and their surrounding immune microenvironment nowadays can be employed as a real-time monitoring platform for translational applications such as patient response to therapeutic targets, including immunotherapy. This study aimed to investigate the expression profiling of these genes along with immunotherapeutic target molecules in CTCs and peripheral blood mononuclear cells (PBMCs) in patients with colorectal carcinoma (CRC). Expression of , , , , and immunotherapeutic target molecules , , and in CTCs and PBMCs were analysed by qPCR. Their expression in high versus low CTC-positive patients with CRC was compared and clinicopathological correlations between these patient groups were analysed. CTCs were detected in 61% (38 of 62) of patients with CRC. The presence of higher numbers of CTCs was significantly correlated with advanced cancer stages ( = 0.045) and the subtypes of adenocarcinoma (conventional vs. mucinous, = 0.019), while being weakly correlated with tumour size ( = 0.051). Patients with lower numbers of CTCs had higher expression of . Higher expression in CTCs was negatively correlated with tumour perforation ( = 0.029), lymph node status ( = 0.037), distant metastasis ( = 0.046) and overall staging ( = 0.004). was highly expressed in both CTCs and PBMCs. In addition, expression was positively correlated with ( = 0.6878, = 0.002) in the enriched CTC fraction. Dysregulation of in CTCs might evade the immune system by altering the expression of , providing new insights into the selection of therapeutic targets at the onset of the disease. Monitoring CTCs counts, as well as gene expression profiling of PBMCs, can be helpful in predicting tumour progression, patient outcome and treatment.