CEACAM5 overexpression is a reliable characteristic of CD133-positive colorectal cancer stem cells

Gisina, A. M.; Novikova, Svetlana; Ys, Kim; Сидоров, Д. В.; Bykasov, S. A.; Волченко, Н. Н.; Каприн, А. Д.; Zgoda, Victor G.; Yarygin, K N; Lupatov, A. Yu.

doi:10.3233/cbm-203187

Cited by 16 publications

(8 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the cell lines did not express the plasma membrane CD133 at all, including three other tested colorectal cell lines. These data appear to contradict our clinical observations showing that just one among 30 colon cancer patients’ samples lacked CD133-positive cells [ 30 ]. Like in cell lines, in individual tumor samples, the CD133-positive share varied in broad limits: from 1 to 65%.…”

Section: Discussioncontrasting

confidence: 92%

TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype

Potashnikova

Gisina

et al. 2022

IJMS

View full text Add to dashboard Cite

CD133 is an extensively studied marker of the most malignant tumor cell population, designated as cancer stem cells (CSCs). However, the function of this glycoprotein and its involvement in cell regulatory cascades are still poorly understood. Here we show a positive correlation between the level of CD133 plasma membrane expression and the proliferative activity of cells of the Caco-2, HT-29, and HUH7 cancer cell lines. Despite a substantial difference in the proliferative activities of cell populations with different levels of CD133 expression, transcriptomic and proteomic profiling revealed only minor distinctions between them. Nonetheless, a further in silico assessment of the differentially expressed transcripts and proteins revealed 16 proteins that could be involved in the regulation of CD133 expression; these were assigned ranks reflecting the apparent extent of their involvement. Among them, the TRIM28 transcription factor had the highest rank. The prominent role of TRIM28 in CD133 expression modulation was confirmed experimentally in the Caco2 cell line clones: the knockout, though not the knockdown, of the TRIM28 gene downregulated CD133. These results for the first time highlight an important role of the TRIM28 transcription factor in the regulation of CD133-associated cancer cell heterogeneity.

show abstract

Section: Discussioncontrasting

confidence: 92%

TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype

Potashnikova

Gisina

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…2 A). Based on the marker genes expressed by different cells (CSCs (TFF3 31 , AGR2 32 , KRT8 33 , KRT18 34 , 35 ), cancer cells (EPCAM 36 , PIGR 37 , CEACAM5 38 ), CD4 + T cells (IL7R 39 , SARAF 40 , LTB 41 ), CD8 + T cells (CCL5 42 , RORA 43 , GZMA 44 ), fibroblasts (COL1A1 45 , COL3A1 45 , DCN 46 ), B cells (CD79A 47 , MS4A1 48 , CD37 49 ), macrophages (C1QA 50 , LYZ 51 , CD68 52 ), mast cells (KIT 53 , CPA3 54 , TPSAB1 55 ), plasma cells (JCHAIN 42 , MZB1 42 ), neutrophils (S100A8 56 , S100A9 57 , CXCL8 58 ), mesenchymal stem cells (STMN1 59 , PTTG1 60 , HMGB2 61 ), endothelial cells (PLVAP 62 , VWF 63 , PECAM1 64 ), smooth muscle cells (TAGLN 65 , RGS5 66 , ACTA2 67 ), we identified 13 cell types in the CRC samples (Fig. 2 B), with the expression of their marker genes as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells

Wu,

Li,

et al. 2024

Sci Rep

View full text Add to dashboard Cite

The prognosis for patients with colorectal cancer (CRC) remains worse than expected due to metastasis, recurrence, and resistance to chemotherapy. Colorectal cancer stem cells (CRCSCs) play a vital role in tumor metastasis, recurrence, and chemotherapy resistance. However, there are currently no prognostic markers based on CRCSCs-related genes available for clinical use. In this study, single-cell transcriptome sequencing was employed to distinguish cancer stem cells (CSCs) in the CRC microenvironment and analyze their properties at the single-cell level. Subsequently, data from TCGA and GEO databases were utilized to develop a prognostic risk model for CRCSCs-related genes and validate its diagnostic performance. Additionally, functional enrichment, immune response, and chemotherapeutic drug sensitivity of the relevant genes in the risk model were investigated. Lastly, the key gene RPS17 in the risk model was identified as a potential prognostic marker and therapeutic target for further comprehensive studies. Our findings provide new insights into the prognostic treatment of CRC and offer novel perspectives for a systematic and comprehensive understanding of CRC development.

show abstract

“…CEACAM5 is a cell-surface glycoprotein that is normally expressed on epithelial cells in numerous organ systems ( 23 ). The high expression of CEACAM5 in colorectal cancer cells is closely associated with the CD133-positive colorectal cancer stem cell phenotype ( 24 ). ENO2 functions not only as a glycolysis enzyme but also as a critical activator of other oncogenic pathways ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

Liu

Wang

et al. 2022

Front. Med.

View full text Add to dashboard Cite

BackgroundColon adenocarcinoma (COAD) is a frequent malignancy of the digestive system with a poor prognosis and high mortality rate worldwide. Intratumor heterogeneity (ITH) is associated with tumor progression, poor prognosis, immunosuppression, and therapy resistance. However, the relationship between ITH and prognosis, the immune microenvironment, and the chemotherapy response in COAD patients remains unknown, and this knowledge is urgently needed.MethodsWe obtained clinical information and gene expression data for COAD patients from The Cancer Genome Atlas (TCGA) database. The DEPTH2 algorithm was utilized to evaluate the ITH score. X-tile software was used to determine the optimal cutoff value of the ITH score. The COAD patients were divided into high- and low-ITH groups based on the cutoff value. We analyzed prognosis, tumor mutation burden (TMB), gene mutations, and immune checkpoint expression between the high- and low-ITH groups. Differentially expressed genes (DEGs) in the high- and low-ITH groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. We performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to screen the prognosis-related genes for the construction of an ITH-related prognostic signature. The nomogram was used to predict the overall survival (OS) of COAD patients. The protein–protein interaction (PPI) network was constructed by using the GeneMANIA database. Principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were employed to explore the differences in biological pathway activation status between the high- and low-risk groups. The proportion and type of tumor-infiltrating immune cells were evaluated by the CIBERSORT and ESTIMATE algorithms. Additionally, we assessed the chemotherapy response and predicted small-molecule drugs for treatment. Finally, the expression of the prognosis-related genes was validated by using the UALCAN database and Human Protein Atlas (HPA) database.ResultsThe OS of the high-ITH group was worse than that of the low-ITH group. A positive correlation between ITH and TMB was identified. In subgroups stratified by age, gender, and tumor stage, the OS of the low-ITH group remained better than that of the high-ITH group. There were dramatic differences in the mutated genes, single nucleotide variant classes, variant types, immune checkpoints and cooccurring and mutually exclusive mutations of the DEGs between the high- and low-ITH groups. Based on the DEGs between the high- and low-ITH groups, we constructed a five-gene signature consisting of CEACAM5, ENO2, GABBR1, MC1R, and SLC44A4. The COAD patients were divided into high- and low-risk groups according to the median risk score. The OS of the high-risk group was worse than that of the low-risk group. The nomogram was used to accurately predict the 1-, 3- and 5-year OS of COAD patients and showed good calibration and moderate discrimination ability. The stromal score, immune score, and ESTIMATE score of the high-risk group were significantly higher than those of the low-risk group, whereas tumor purity showed the opposite trend. The patients classified by the risk score had distinguishable sensitivity to chemotherapeutic drugs. Finally, two public databases confirmed that CEACAM5 and SLC44A4 were upregulated in normal tissues compared with COAD tissues, and ENO2, GABBR1, and MC1R were upregulated in COAD tissues compared with normal tissues.ConclusionOverall, we identified an ITH-related prognostic signature for COAD that was closely related to the tumor microenvironment and chemotherapy response. This signature may help clinicians make more personalized and precise treatment decisions for COAD patients.

show abstract

CEACAM5 overexpression is a reliable characteristic of CD133-positive colorectal cancer stem cells

Cited by 16 publications

References 44 publications

TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype

TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype

Integration of single-cell sequencing and bulk RNA-seq to identify and develop a prognostic signature related to colorectal cancer stem cells

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma

Contact Info

Product

Resources

About