Biomarker For Colorectal Cancer Research Articles

Multiomics Approach Identifies Key Proteins and Regulatory Pathways in Colorectal Cancer.

The prevalence rate of colorectal cancer (CRC) has dramatically increased in recent decades. However, robust CRC biomarkers with therapeutic value for early diagnosis are still lacking. To comprehensively reveal the molecular characteristics of CRC development, we employed a multiomics strategy to investigate eight different types of CRC samples. Proteomic analysis revealed 2022 and 599 differentially expressed tissue proteins between CRC and control groups in CRC patients and CRC mice, respectively. In patients with colorectal precancerous lesions, 25 and 34 significantly changed proteins were found between patients and healthy controls in plasma and white blood cells, respectively. Notably, vesicle-associated membrane protein-associated protein A (VAPA) was found to be consistently and significantly decreased in most types of CRC samples, and its level was also significantly correlated with increased overall survival of CRC patients. Furthermore, 37 significantly enriched pathways in CRC were further validated via metabolomics analysis. Ten VAPA-related pathways were found to be significantly enriched in CRC samples, among which PI3K-Akt signaling, central carbon metabolism in cancer, cholesterol metabolism, and ABC transporter pathways were also enriched in the premalignant stage. Our study identified VAPA and its associated pathways as key regulators, suggesting their potential applications in the early diagnosis and prognosis of CRC.

Dysregulation of saliva and fecal microbiota as novel biomarkers of colorectal cancer

The aim of this study was to investigate the biomarkers of salivary and fecal microbiota in Colorectal cancer (CRC). Initially, the study scrutinized the microbial community composition disparities among groups. Utilizing Lasso analysis, it sifted through operational taxonomic units (OTUs) to pinpoint distinctive features. Subsequently, by intersecting feature OTUs across groups, it curated a set of core-shared OTUs and devised a corresponding network. Concluding with functional enrichment analysis, the research delved into the divergent biological functions of these microbial communities within the studied groups. Analysis revealed higher bacterial diversity in saliva compared to feces, with distinct differences at both phylum and genus levels. Feces primarily contained Firmicutes, while saliva was dominated by Bacteroidetes and Proteobacteria. Notably, Escherichia-Shigella and Fusobacterium in feces and Streptococcus in saliva showed increasing abundance from average to adenoma to colorectal cancer. Specific dominant flora was identified within and between groups, including CRC and adenomas across different stages. Seventeen core shared OTUs were identified, and networks of shared OTUs were constructed for each group. Functional enrichment analysis highlighted distinct microbial community functions among the groups. This study’s findings on characteristic OTUs in saliva and fecal samples offer valuable insights for distinguishing between healthy individuals, adenoma patients, and those with colorectal cancer. This study identified distinctive OTUs in saliva and feces to distinguish between healthy individuals, adenoma patients, and those with CRC, offering a valuable diagnostic reference.

The Role of Leukocyte Immunoglobulin Receptor B2 Overexpression as a Novel Biomarker and Potential Therapeutic Agent for Colorectal Cancer

The Role of Leukocyte Immunoglobulin Receptor B2 Overexpression as a Novel Biomarker and Potential Therapeutic Agent for Colorectal Cancer

Identification and Validation of Serum Biomarkers to Improve Colorectal Cancer Diagnosis.

The pressing need for reliable biomarkers in colorectal cancer (CRC) diagnosis and prognosis is a major global health concern. Current diagnostic methods rely heavily on invasive procedures like colonoscopy, and existing biomarkers such as Carbohydrate Antigen 19-9 (CA19-9) and Carcinoembryonic Antigen (CEA) exhibit limitations in accuracy and specificity. This study aims to identify and validate novel biomarkers that can enhance the early detection and diagnostic precision of CRC while overcoming the shortcomings of conventional biomarkers. Leveraging advancements in genomic and proteomic technologies, gene expression datasets were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We identified differentially expressed genes (DEGs) and conducted further analyses, including Gene Ontology (GO) enrichment and Protein-Protein Interaction (PPI) network construction. Five promising biomarkers-INHBA, MMP7, PSAT1, SLC7A5, and TGFBI-were selected based on their robust performance in Receiver Operating Characteristic (ROC) curve analysis. Serum concentrations of these biomarkers were measured in 200 CRC patients and 100 healthy controls. The study revealed significantly elevated expression levels of the selected biomarkers in CRC tissues compared to normal tissues. Additionally, serum concentrations of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI were notably higher in CRC patients than in healthy individuals, with Area Under the Curve (AUC) values ranging from 0.8361 to 0.9869 indicating high diagnostic accuracy. Optimal cutoff values for diagnosis ranged from 38.9 pg/mL to 280.7 pg/mL, yielding sensitivity and specificity values between 74.5% and 92.9%. The findings underscore the potential of INHBA, MMP7, PSAT1, SLC7A5, and TGFBI as effective non-invasive biomarkers for CRC detection. Their elevated serum concentrations and robust discriminatory abilities highlight their promise in improving diagnostic accuracy and patient outcomes compared to traditional biomarkers. The identification and validation of these novel biomarkers represent a significant advancement in CRC diagnosis and management. Further studies are required to validate their clinical applicability in larger cohorts and to elucidate their functional roles in CRC pathogenesis, ultimately enhancing diagnostic strategies and personalized treatment approaches.

Hsa_circ_0000520 Serves as a Prognostic Biomarker for Colorectal Cancer and Promotes in the Disease Progression.

Colorectal cancer (CRC) constitutes one of the prevalent malignancies within the gastrointestinal tract and serves as a primary contributor to cancer-related mortalities. This investigation sought to investigate the expression and prognostic significance of hsa_circ_0000520 in CRC and to evaluate its impact on the onset of CRC. The levels of hsa_circ_0000520 were measured via quantitative real-time polymerase chain reaction (qRTPCR). To delve into the mechanism through which circ_0000520 impacts CRC and to assess the cellular behavior of CRC cells, a series of experiments including the CCK-8, transwell assay, flow cytometer assay, cell cloning formation, dual-luciferase reporter assay, and bioinformatics method were performed. The expression levels of hsa_circ_0000520 were markedly elevated in CRC cells and tissue specimens, and this elevation was correlated with a low survival rate. hsa_circ_0000520 affected CRC cell function via the miR-542-3p/MYH9 axis, thus exacerbating cancer progression. hsa_circ_0000520 functions as a predictive biomarker for the prognosis of CRC and participates in its progression. hsa_ circ_0000520 emerges as a new treatment strategy for CRC patients.

Impact of obesity and diabetes on colorectal cancer in Saudi Arabia is associated with liver γ‑glutamyl transferase abnormality.

Colorectal cancer (CRC) is a leading global cause of death. In Saudi Arabia, it is the most common cancer among men and the third most common among women. Obesity, diabetes and CRC have become significant health concerns. The present study aimed to explore the connection between liver function markers, obesity and diabetes in patients with CRC. In addition to exploring whether the incidence of CRC had increased in Saudi Arabia. The present study conducted a retrospective chart review based on data from the Saudi Ministry of National Guard Hospitals. Clinical laboratory assays of patients with CRC with obesity and/or diabetes between 2015 and 2021 were analysed, and various factors were considered. This study found that CRC is more prevalent in overweight and obese individuals, primarily aged 50 years and older. Diabetes was more common in patients with CRC (61.76%) compared with non-diabetic individuals (38.24%). Additionally, the protein γ-glutamyl transferase might serve as a potential biomarker for CRC in overweight and obese patients. Notably, the age of CRC diagnosis in Saudi Arabian patients in the present study was lower than previously reported. The present study provided insight into the relationship between obesity, diabetes and liver function markers in Saudi Arabian patients with CRC. It also highlighted the increasing incidence of CRC in Saudi Arabia, emphasizing the need for further attention and research.

Novel surfactant-free electro-nanofabricating strategy for highly sensitive and selective colorectal cancer MicroRNA analysis

A label-free nanostructured electrochemical biosensor utilizing graphene quantum dot (GQD) decorated with gold nanoparticles (AuNPs), known as Au-GQD-NS, is presented to colorectal cancer (CRC) biomarker early detection, micro RNA-223 (miR-223). Thiolated DNA probes (Cap-223) are immobilized onto a fabricated and highly conductive nanostructure platform, which improves accessibility and miR-223 recognition. To analyze the nanostructured surface, various sophisticated techniques such as FESEM, EDAX, AFM, and electrochemical approaches are employed. Electrochemical approaches including DPV, EIS, and CV are applied to investigate the electroactivity of substrate, immobilization of Cap-223 on Au-GQD-NPs and subsequent hybridization with the miR-223. The electro-nanofabricated biosensor showcases a wide linear detection range (zepto M to nano M) with an impressively suitable LOD (0.024 atto M). The biosensor selectivity is demonstrated through discrimination studies between target and mismatched miRNA sequences (miR-9 and miR-21). This biosensor also exhibits significant potential for quantitative evaluation of miR-223 in real samples, enabling its applications in point-of-care (POC) detection of CRC. In addition, the Au-GQD-NS substrate is nano-fabricated in absent of surfactants and stabilizers, providing secure anchors for immobilization of cap-223. The well-established strategies for cap-223 immobilization and hybridization with miR, combined with superior electron exchange rate compared to uncovered FTO, upgrade the biosensor’s execution. Significantly, the biosensor demonstrates efficient miR-223 detection in human serum. Overall, this nano-fabricated biosensor shows great promise for miR-based early detection of CRC, and therefore, offering great sensitivity, selectivity, and favorable hydrophilicity for translational medicine investigation and clinical applications.

Detection of genetic determinants of potentially oncogenic representatives of the intestinal microbiota as biomarkers of colorectal cancer

Relevance. Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. Non-invasive diagnostic methods based on the determination of hidden blood in the stool (fecal immunochemical test, guaiac test), which have been proven to be effective in clinical studies, are used for CRC screening. However, a significant disadvantage of the available non-invasive diagnostic methods is the low sensitivity in detecting the oncological process at the early stages. A number of recent studies discuss the relationship between the disease and various potentially oncogenic microorganisms in the human intestinal tract, which can be used to expand the arsenal of non-invasive methods for diagnosing CRC based on molecular genetic examination of a stool sample to identify oncogenic microorganisms. The aim of this study was to evaluate the possibility of using genetic determinants of potentially oncogenic microorganisms as markers for colorectal cancer, based on a comparison of their prevalence in groups of patients with colorectal cancer, facultative precancerous diseases and patients without intestinal pathology. Materials and methods. 215 participants were included in the "case–control" study: 70 patients with newly diagnosed colorectal cancer, 70 patients with inflammatory bowel disease, 75 participants without diagnosed intestinal pathology. Polymerase chain reaction (PCR) was used to identify and detect genes of potentially oncogenic microorganisms. Results and discussion. An association was found between CRC and the presence of the Bacteroides fragilis fragilisin gene (OR 7.00; 95% CI: 2.55–22.50; p 0.001), species-specific genes of the periodontal pathogenic microorganisms Fusobacterium nucleatum (OR 5.61; 95% CI: 2.87–11.30; p 0.001) and Porphyromonas gingivalis (OR 16.3; 95% CI: 4.33–106.00; p 0.001), the clbB gene of pks pathogenicity island of the Enterobacteria (OR 3.44; 95% CI: 1.39–8.51; p = 0.010). Conclusion. The presence of genetic markers of potentially oncogenic bacterial species and genotypes in the gut microbiome is associated with colorectal cancer. The results obtained support the possibility of using molecular genetic detection of the studied potentially oncogenic microorganisms as a method for non-invasive diagnosis of CRC.

Forced Overexpression and Knockout Analysis of SLC30A and SLC39A Family Genes Suggests Their Involvement in Establishing Resistance to Cisplatin in Human Cancer Cells.

The metabolism of zinc and manganese plays a pivotal role in cancer progression by mediating cancer cell growth and metastasis. The SLC30A family proteins SLC30A3 and SLC30A10 mediate the efflux of zinc, manganese, and probably other transition element ions outside the cytoplasm to the extracellular space or into intracellular membrane compartments. The SLC39A family members SLC39A8 and SLC39A14 are their functional antagonists that transfer these ions into the cytoplasm. Recently, the SLC30A10 gene was suggested as a promising methylation biomarker of colorectal cancer. Here, we investigated whether forced overexpression or inactivation of SLC30A and SLC39A family genes has an impact on the phenotype of cancer cells and their sensitivity to cancer therapeutics. In the human colon adenocarcinoma HCT-15 and duodenal adenocarcinoma HuTu80 cell lines, we generated clones with knockouts of the SLC39A8 and SLC39A14 genes and forced overexpression of the SLC30A3, SLC30A10, and SLC39A8 genes. Gene expression in the mutant and control cells was assessed by RNA sequencing. The cell growth rate, mitochondrial activity, zinc accumulation, and sensitivity to the drugs cetuximab and cisplatin were investigated in functional tests. Overexpression or depletion of SLC30A or SLC39A family genes resulted in the deep reshaping of intracellular signaling and provoked hyperactivation of mitochondrial respiration. Variation in the expression of the SLC30A/SLC39A genes did not increase the sensitivity to cetuximab but significantly altered the sensitivity to cisplatin: overexpression of SLC30A10 resulted in an ~2.7-4 times increased IC50 of cisplatin, and overexpression of SLC30A3 resulted in an ~3.3 times decreased IC50 of cisplatin. The SLC30A/SLC39A genes should be considered as potential cancer drug resistance biomarkers and putative therapeutic targets.

Establishment of liquid biopsy procedure for the analysis of circulating cell free DNA, exosomes, RNA and proteins in colorectal cancer and adenoma patients

Liquid biopsy has an underexplored diagnostic potential in colorectal cancer (CRC). Sufficient quantity and quality of its elements (circulating cell-free DNA (ccfDNA), exosomes and exosomal RNA) are essential for accurate results. The present study aims to establish the optimal protocol for handling liquid biopsy samples. Samples were obtained by collecting peripheral blood from colorectal adenoma patients in CellSave tubes. Plasma was separated within six hours using differential centrifugation and aliquots stored at – 20/– 80 °C until further processing. Three methods for isolation of ccfDNA, and two combinations of kits for isolation of exosomes and exosomal RNA were tested. The quality and quantity of ccfDNA isolates were evaluated. Exosomes were characterised by determining size, concentration, and total and specific protein content. Expression of chosen microRNAs, miR-19a-3p and miR-92-3p, which have been implicated in CRC progression, were determined. The vacuum-column-based kit showed the highest quantities of isolated ccfDNA (P-value < 0.001). Kits for exosome isolation significantly differed in size (P-value = 0.016), concentration (P-value = 0.016) and protein content (P-value = 0.016). There was no significant difference in expressions of miR-19a-3p (P-value = 0.219) and miR-92a-3p (P-value = 0.094) between the two isolation kits. The new, adapted protocol described, enables simultaneous analysis of multiple elements when investigating potential biomarkers of CRC.

The ketogenic diet modulates tumor-associated neutrophil polarization via the AMOT-YAP/TAZ axis to inhibit colorectal cancer progression

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), the prognosis for late-stage patients remains poor, highlighting the urgent need for new preventive and therapeutic strategies. Recent studies have focused on the ketogenic diet (KD) and its metabolite, β-hydroxybutyrate (BHB), for their tumor-suppressive effects and modulation of inflammatory responses. Using the azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced mouse CRC model, we found that the ketogenic diet and BHB inhibit pro-tumor N2-type tumor-associated neutrophils (TANs) while promoting the polarization of TANs towards the anti-tumor N1 type. This shift in TANs polarization affects tumor growth and metastasis. The underlying mechanism involves BHB acting on the intracellular receptor histone deacetylases 3 (HDAC3), which modulates the activation of the AMOT-YAP/TAZ axis, leading to the inhibition of pro-carcinogenic factor transcription and release. Moreover, clinical cohort data corroborate these findings, showing that CRC patients with elevated BHB levels have significantly lower rates of lymph node involvement, which is associated with a higher infiltration ratio of anti-carcinogenic N1-type TANs in the tumor microenvironment (TME). These results suggest that BHB levels could serve as a prognostic biomarker for CRC. In conclusion, our findings indicate that BHB derived from KD regulates TANs polarization in CRC via the HDAC3-AMOT-YAP/TAZ axis, effectively inhibiting tumor growth and metastasis. These insights establish a novel theoretical basis for employing the KD in the treatment of CRC and for developing cancer adjuvant immunotherapy strategy based on the polarization of neutrophils.

Effect of MPP2 and its DNA methylation levels on prognosis of colorectal cancer patients

Colorectal cancer is one of the common malignant tumors with poor prognosis, which is partly due to the lack of an effective biomarker. The purpose of this study is to explore the impact of membrane palmitoylated protein (MPP2) on the prognosis of colorectal cancer patients. We obtained transcriptome data and DNA methylation data of 380 colorectal cancer patients from the Cancer Genome Atlas (TCGA). Then we used a series of bioinformatics analysis methods to reveal the relationship between MPP2 expression, DNA methylation sites, prognosis, immune checkpoint and clinical characteristics of patients. Finally, in vitro experiment and the meta-analysis of thousands of patients further confirmed the impact of MPP2 on the prognosis of colorectal cancer patients and cell migration and proliferation. The expression level of MPP2 is negatively regulated by its DNA methylation sites, which leads to its low expression in colorectal cancer. High expression of MPP2 is an independent prognostic risk factor, which may be a biomarker for colorectal cancer. Moreover, the expression of MPP2 shows a close relationship with immune checkpoint or immune cells infiltration, especially CD4+T cells. In addition, meta-analysis involving 1584 patients from four different data further confirmed that MPP2 was a risk factor for colorectal cancer. Finally, knockdown of MPP2 could significantly inhibit the proliferation of SW480 cells via mTOR signaling pathway. This study was the first to suggest that MPP2 may become a promising biomarker, and has an important role in immune checkpoint or immune cell infiltration in colorectal cancer.

Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.

Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously. We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC. We conducted methyl-CpG binding domain isolated genome sequencing (MiGS) on CpG island methylation phenotype (CIMP)-positive (n=3) and CIMP-negative CRC tissues (n=3) and their corresponding normal adjacent tissues. Subsequently, by utilizing both the aforementioned data and public datasets, we identified a set of promising methylated sDNA markers for CRC. Next, we validated 5 of these genes using pyrosequencing in CRC patients (n=31). Then, we developed a combined diagnostic model (CDM) for CRC based on the methylation status of PRDM12, FOXE1, and SDC2 by a Training cohort (n=231). Finally, the performance of CDM was evaluated in an independent multicenter Validation cohort (n=800). A total of 1062 participants were included in this study. The area under the curve (AUC) of the CDM was 0.979 (95% CI: 0.960-0.997), and the optimal sensitivity and specificity were 97.35% and 99.05%, respectively, in the training cohort (n=231). In the independent validation cohort (n=800), the AUC was 0.950 (95% CI: 0.927-0.973), along with the optimal sensitivity of 92.75% and specificity of 97.21%. When CRC and advanced adenoma (AAD) were used as diagnostic targets, the model AUC was 0.945 (95% CI: 0.922-0.969), with an optimal sensitivity of 91.89% and a specificity of 95.21%. The model sensitivity for nonadvanced adenoma patients was 68.66%. The sDNA diagnostic model CDM, developed from both CIMP-P and CIMP-N, exhibited exceptional performance in CRC and could serve as a potential alternative strategy for CRC screening.

CD248 Cleaved Form in Human Colorectal Cancer Stroma: Implications for Tumor Behavior and Prognosis

CD248 (endosialin/tumor endothelial marker 1) is upregulated in cancer, including colorectal cancer (CRC), but its exact role in tumor progression remains to be elucidated. Previous studies have shown that the extracellular domain of CD248 mediates the interaction between tumor cells and extracellular matrix proteins and that interfering with this interaction may reduce tumor invasion and migration activities. We have examined the expression of CD248 in 117 human CRC samples by immunohistochemistry and investigated the association with various clinicopathologic features, including the occurrence of metastasis intratumoral immune cell density and overall survival. Of the 117 specimens analyzed, 76.1% (89/117) exhibited CD248-high stromal expression, whereas 23.1% (28/117) demonstrated CD248-low stromal expression. Interestingly, we detected the presence of a cleaved form of CD248, which appears to accumulate in the stromal extracellular matrix. A higher metastasis rate (lymph node and distant) was observed in the CD248-low group (21/28, 75.0% vs 44/89, 49.4%; P = .02). In addition, CD248-low tumors had fewer CD163-positive macrophages and FoxP3-positive regulatory T cells (P < .05) with no significant difference in CD8-positive T-cell infiltration and PD-L1 expression between the groups (P > .05). Finally, overall survival was lower in CD248-low tumors than in CD248-high tumors, with 5-year survival rates of 35.7% and 57.3%, respectively (P = .01). In a multivariate analysis, the hazard ratio of CD248-low tumors vs CD248-high tumors was 1.93 (95% CI, 1.09-3.41; P = .02). Our findings suggest that CD248 stromal expression may influence the tumor microenvironment, impacting tumor behavior and prognosis, and can serve as a promising prognostic biomarker in CRC.

Chondroitin polymerizing factor (CHPF) promotes the progression of colorectal cancer through ASB2-mediated ubiquitylation of SMAD9.

Chondroitin polymerizing factor (CHPF) has been reported to play a pivotal role in the progression of multiple cancers, however, the relationship between CHPF and colorectal cancer (CRC) progression has not been fully understood. The current study revealed that CHPF expression was upregulated in patients with CRC and correlated with an unfavorable prognosis. Also, CHPF knockdown effectively suppressed the viability and mobility of CRC cells and the growth of xenograft tumors. Additionally, SMAD9 was identified as a downstream target of CHPF. SMAD9 knockdown successfully abrogated the promotion of CHPF overexpression in CRC progression, indicating that CHPF regulated the development of CRC through SMAD9. Mechanistically, SMAD9 is ubiquitinated by ASB2, and the regulatory effect of CHPF on SMAD9 activity was exerted via its mediation of ASB2. Collectively, CHPF functioned as a promising prognostic biomarker and tumor-promoter of CRC by regulating the ASB2-mediated ubiquitination of SMAD9.

Circ_0089761 accelerates colorectal cancer metastasis and immune escape via miR-27b-3p/PD-L1 axis.

Circular RNAs have been implicated as critical regulators in the initiation and progression of colorectal cancer (CRC). This study was intended to elucidate the functional significance of the circ_0089761/miR-27b-3p/programmed cell death ligand 1 (PD-L1) axis in CRC. Our findings indicated that circ_0089761 expression was significantly elevated in CRC tissues and cell lines. Furthermore, the high expression of circ_0089761 was correlated with TNM stage and tumor size. Silencing circ_0089761 inhibited CRC cell proliferation, migration, and invasion, and increased apoptosis. Mechanistically, circ_0089761 facilitated its biological function by binding to miR-27b-3p to upregulate PD-L1 expression in CRC. Coculture experiments confirmed that low expression of circ_0089761 impeded CD8 + T cell apoptosis and depletion, activated CD8 + T cell function, and increased secretion of the immune effector cytokines IFN-γ, TNF-α, perforin, and granzyme-B. MiR-27b-3p inhibition or PD-L1 overexpression partially impeded CD8 + T cell function. The circ_0089761/miR-27b-3p/PD-L1 axis is postulated to exert pivotal functions in the mechanistic progression of CRC. Furthermore, it holds promising prospects as a feasible biomarker and therapeutic target for CRC.

Comprehensive Analysis and Experimental Validation of HEPACAM2 as a Potential Prognosis Biomarker and Immunotherapy Target in Colorectal Cancer.

The role of HEPACAM family member 2 (HEPACAM2) is unclear in colorectal cancer (CRC). The objective of this study was to perform an extensive examination of HEPACAM2 and validate it experimentally in CRC. This study investigated the significance of HEPACAM2 in CRC and its potential diagnostic utility utilizing data from the Cancer Genome Atlas (TCGA) database. Additionally, the study examined potential regulatory networks involving HEPACAM2, including its associations with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), mRNA expression-based stemness index (mRNAsi), and drug sensitivity in CRC. The expression of HEPACAM2 was further validated using the GSE89076 dataset, and quantitative reverse transcription PCR (qRT-PCR) was employed to confirm HEPACAM2 expression levels in six pairs of CRC tissue samples. HEPACAM2 exhibited abnormal expression patterns in various types of cancer, including CRC. A decrease in HEPACAM2 expression levels in CRC was found to be significantly correlated with the T stage (p < 0.001). Reduced HEPACAM2 expression in CRC patients was also linked to poorer overall survival (OS) (p = 0.007). The expression levels of HEPACAM2 in CRC patients were identified as an independent prognostic factor (p = 0.016). Furthermore, HEPACAM2 was associated with TCF-dependent signaling in response to WNT, G2/M checkpoints, and other pathways. The expression of HEPACAM2 in CRC was found to be associated with immune infiltration, immune checkpoint genes, TMB / MSI, and mRNAsi. Additionally, the expression of HEPACAM2 in CRC was significantly and inversely correlated with the drug sensitivities to gw772405x and 6-phenyl-6h-indeno[1,2-c]isoquinoline-5,11-dione. qRT-PCR confirmed that the expression level of HEPACAM2 was found to be lowly expressed in CRC tissues. These findings suggest that HEPACAM2 may serve as a potential prognostic biomarker and immunotherapeutic target for CRC patients.

GUCA2A dysregulation as a promising biomarker for accurate diagnosis and prognosis of colorectal cancer

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein–Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

Exploring the Therapeutic Potential of Ginkgo biloba Polyphenols in Targeting Biomarkers of Colorectal Cancer: An In-silico Evaluation.

Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide, driving the need for effective anticancer therapies with fewer side effects. The exploration of Ginkgo biloba, a natural source, offers a hopeful avenue for novel treatments targeting key colorectal biomarkers involved in CRC treatment. The aim of this study was to explore the binding affinity of natural molecules derived from G. biloba to essential biomarkers associated with CRC, including Kirsten rat sarcoma virus, neuroblastoma RAS mutations, serine/threonine-protein kinase B-Raf, phosphatidylinositol 3'-kinase, and deleted colorectal cancer, using molecular docking. The focus of this research was to evaluate how effectively these molecules bind to specified targets in order to identify potential inhibitors for the treatment of CRC. A total of 152 polyphenolic compounds from G. biloba were selected and subjected to molecular docking simulations to evaluate their interactions with CRC-related biomarkers. The docking results were analysed to identify ligands exhibiting strong affinities towards the targeted genes, suggesting potential inhibitory effects. Docking simulations unveiled the strong binding affinities between selected polyphenolic compounds derived from G. biloba and genes associated with CRC. The complex glycoside structures that are found in flavonols are of significant importance. These compounds, including derivatives with distinctive arrangements, exhibited promising docking scores, signifying substantial interactions with the targeted biomarkers. The study demonstrates the potential of G. biloba-derived molecules as effective anticancer agents for colorectal cancer. The identified ligands exhibit strong interactions with crucial CRC-related biomarkers, suggesting potential inhibition ability. Further in vitro and in vivo investigations are needed to validate and build upon these promising findings, advancing the development of novel and efficient CRC therapies.

The dysregulation and clinical relevance of lncRNAs MYOSLID and SFTA1P in colorectal cancer patients.

Colorectal cancer (CRC) is a very common cancer worldwide. CRC is characterized by some changes in the expression of oncogenic and tumor suppressor genes. These changes are associated with dysregulation of non-coding RNAs, including long non-coding RNAs (lncRNAs). LncRNAs are heterogeneous non-coding molecules without open reading frames. LncRNAs have been established as regulators in the development of CRC and clinical biomarkers for the CRC detection. In this project, we investigated the expression changes of two new lncRNAs named SFTA1P and MYOSLID in CRC patients. 30 samples of CRC tissue and 30 samples of normal tissue adjacent to the cancer tissue were obtained from patients. RNA extraction from tissue samples was performed using RNAX plus. ExcelRT™ Reverse Transcription Kit (SymBio, Korea) was used for cDNA synthesis. RealQ Plus 2x Master Mix Green Without ROX™ was used to perform a quantitative PCR (qPCR). REST, and SPSS software were used for statistical analysis. Our result demonstrated that lncRNAs MYOSLID and SFTA1P were significantly up-regulated in tumor tissues compared to healthy tissues with a fold change of 13.43 and 5.33 (P < 0.05) respectively. Based on the analysis of ROC curve, MYOSLID (AUC = 0.946, P < 0.0001, SE =0.0035) and SFTA1P (AUC = 0.800, P < 0.0001, SE = 0.059) were indicated as potential clinical hallmarks for CRC patients. According to the results obtained from this research, lncRNAs SFTA1P and MYOSLID can be suggested as molecular biomarkers for the CRC diagnosis.