ABCG2 Gene and ABCG2 Protein Expression in Colorectal Cancer—In Silico and Wet Analysis

Abstract

ABCG2 (ATP-binding cassette superfamily G member 2) is a cell membrane pump encoded by the ABCG2 gene. ABCG2 can protect cells against compounds initiating and/or intensifying neoplasia and is considered a marker of stem cells responsible for cancer growth, drug resistance and recurrence. Expression of the ABCG2 gene or its protein has been shown to be a negative prognostic factor in various malignancies. However, its prognostic significance in colorectal cancer remains unclear. Using publicly available data, ABCG2 was shown to be underexpressed in colon and rectum adenocarcinomas, with lower expression compared to both the adjacent nonmalignant lung tissues and non-tumour lung tissues of healthy individuals. This downregulation could result from the methylation level of some sites of the ABCG2 gene. This was connected with microsatellite instability, weight and age among patients with colon adenocarcinoma, and with tumour localization, population type and age of patients for rectum adenocarcinoma. No association was found between ABCG2 expression level and survival of colorectal cancer patients. In wet analysis of colorectal cancer samples, neither ABCG2 gene expression, analysed by RT-PCR, nor ABCG2 protein level, assessed by immunohistochemistry, was associated with any clinicopathological factors or overall survival. An ABCG2-centered protein–protein interaction network build by STRING showed proteins were found to be involved in leukotriene, organic anion and xenobiotic transport, endodermal cell fate specification, and histone methylation and ubiquitination. Hence, ABCG2 underexpression could be an indicator of the activity of certain signalling pathways or protein interactors essential for colorectal carcinogenesis.

SLC38A3 Promotes the Proliferation and Migration of Tumor Cells and Predicts Poor Prognosis in Colorectal Cancer

“…SLC4A4 and SLC9A3 can transport H + and HCO 3 – , respectively, thus affecting tumor cell PH regulation. SLC15A1 has a significant effect on intestinal peptide transport affects intestinal diseases. ,− SLC38A3 is known for its involvement in amino acid transport and is extensively documented in neurological disorders. − Previous studies have explored the role of SLC38A3 in glutamine metabolism and its effect on tumor progression. Our study identified SLC38A3 as a novel prognostic marker gene in CRC, and the knockdown of SLC38A3 in HCT cells inhibited CRC cell proliferation and migration.…”

“…SLC15A1 has a significant effect on intestinal peptide transport affects intestinal diseases. 19 , 22 − 24 SLC38A3 is known for its involvement in amino acid transport and is extensively documented in neurological disorders. 25 − 27 Previous studies have explored the role of SLC38A3 in glutamine metabolism and its effect on tumor progression.…”

The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995–2022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9

“…The aforementioned studies definitely helped us to guide the construction of our study tenets and we are most grateful to their authors for their guidance and direction. Naturally, as technology advances, other biomarkers will come to the fore and we mention some for our readers' interest in References [48,49]. In a relatively recent comprehensive review [50] of IHC staining methods, Adnab-9 was one of 8 other markers selected (p53, β-catenin, COX2, Ki-67, Cyclin D1, Annexin A10, Aldehyde Dehydrogenase Isoform 1A1).…”

Novel Therapeutic Approaches for Colorectal Cancer Treatment

“…The expression of the ABCG2 gene has demonstrated negative prognostic implications in various malignancies, while in CRC, its prognostic significance remains undefined [25][26][27]. By analyzing publicly available datasets, Sałagacka-Kubiak et al demonstrated that ABCG2 is downregulated in colon and rectum adenocarcinomas, exhibiting lower expression levels compared to both adjacent non-malignant tissues [28]. This deregulation is suggested to be associated with the methylation level of specific sites within the ABCG2 gene and correlated with microsatellite instability (MSI), weight, and age, whilst in rectum adenocarcinoma patients, it was linked to tumor localization, population type, and age.…”