Biomarker For Colorectal Cancer Research Articles

Identification of miR-20a as a Diagnostic and Prognostic Biomarker in Colorectal Cancer: MicroRNA Sequencing and Machine Learning Analysis.

The differential expression of miRNAs, a key regulator in many cell signaling pathways, has been studied in various malignancies and may have an important role in cancer progression, including colorectal cancer (CRC). The present study used machine learning and gene interaction study tools to explore the prognostic and diagnostic value of miRNAs in CRC. Integrative analysis of 353 CRC samples and normal tissue data was obtained from the TCGA database and further analyzed by R packages to define the deferentially expressed miRNAs (DEMs). Furthermore, machine learning and Kaplan Meier survival analysis helped better specify the significant prognostic value of miRNAs. A combination of online databases was then used to evaluate the interactions between target genes, their molecular pathways, and the correlation between the DEMs. The results indicated that miR-19b and miR-20a have a significant prognostic role and are associated with CRC progression. The ROC curve analysis discovered that miR-20a alone and combined with other miRNAs, including hsa-mir-21 and hsa-mir-542, are diagnostic biomarkers in CRC. In addition, 12 genes, including NTRK2, CDC42, EGFR, AGO2, PRKCA, HSP90AA1, TLR4, IGF1, ESR1, SMAD2, SMAD4, and NEDD4L, were found to be the highest score targets for these miRNAs. Pathway analysis identified the two correlated tyrosine kinase and MAPK signaling pathways with the key interaction genes, i.e., EGFR, CDC42, and HSP90AA1. To better define the role of these miRNAs, the ceRNA network, including lncRNAs, was also prepared. In conclusion, the combination of R data analysis and machine learning provides a robust approach to resolving complicated interactions between miRNAs and their targets.

Advancements and Challenges in Biomarkers for Colorectal Cancer Detection: A Comprehensive Review

This study provides an overview of the current landscape of biomarkers for colorectal cancer (CRC) detection, focusing on genetic, proteomic, circulating microRNA (miRNA), and metabolomic biomarkers. CRC remains a significant global health challenge, ranking among the most prevalent cancers worldwide and being a leading cause of cancer-related deaths. Despite advancements in screening methods such as colonoscopy, sigmoidoscopy, and fecal occult blood tests (FOBT), the asymptomatic nature of early-stage CRC often results in late diagnoses, negatively impacting patient outcomes. Genetic biomarkers like APC, KRAS, TP53, and microsatellite instability (MSI) play critical roles in CRC pathogenesis and progression. These biomarkers, detectable through polymerase chain reaction, next-generation sequencing, and other advanced techniques, guide early detection and personalized treatment decisions. Proteomic biomarkers such as CEA, CA 19-9, and novel signatures offer insights into CRC’s physiological changes and disease status, aiding prognosis and treatment response assessments through enzyme-linked immunosorbent assay and mass spectrometry. Circulating miRNAs, including miR-21 and miR-92a, present promising non-invasive biomarkers that can be detected in blood and stool samples, reflecting CRC presence, progression, and therapeutic response. Metabolomic biomarkers, encompassing amino acids, lipids, and TCA cycle intermediates, provide further insights into CRC-associated metabolic alterations, which are crucial for early detection and treatment monitoring using mass spectrometry and nuclear magnetic resonance. Despite these advancements, challenges such as biomarker validation, standardization, and clinical utility remain. Future research directions include integrating multi-omics approaches and leveraging technologies like liquid biopsies and AI for enhanced biomarker discovery and clinical application. By addressing these challenges and advancing research in biomarker development, CRC screening and management could potentially be revolutionized, improving patient outcomes and reducing the global burden of this disease.

Exploring the Role of Escherichia coli K-12 in Reducing MIR17HG Expression as a Poor Prognostic Biomarker in Colorectal Cancer

Background: Long noncoding RNAs (lncRNAs) play significant roles in various cellular processes, and alterations in their expression levels can contribute to the pathogenesis of colorectal cancer (CRC). Objectives: This study aims to identify lncRNAs highly associated with poor prognosis in CRC and determine those that exhibit significant expression changes under the influence of Escherichia coli K-12. Methods: Potentially susceptible lncRNAs to expression modulation in the presence of E. coli K-12 were identified by analyzing GSE50040 datasets. Data from the cancer genome Atlas (TCGA) were utilized to assess E. coli K-12-affected lncRNAs with the most significant impact on CRC pathogenesis. The association between the candidate lncRNA and patient prognosis was investigated using clinical data. The co-expression network was employed to identify pathways related to the identified lncRNA via the MsigDB database. To validate the in silico findings, CRC and adjacent normal samples were examined using the RT-qPCR method. Results: Cox regression analysis demonstrated that MIR17HG is a strong biomarker associated with poor prognosis in CRC patients. Increased expression of MIR17HG in cancer samples was correlated with key pathways involving cell proliferation, anti-apoptosis, and metastasis. RT-qPCR results showed that the expression level of MIR17HG in CRC samples was significantly higher than in normal samples. Further analysis revealed that MIR17HG expression is susceptible to suppression by E. coli K-12. Conclusions: High expression of MIR17HG in cancer samples is associated with an increased probability of mortality in CRC patients. Our study highlights the potential of E. coli K-12 to reduce CRC malignancy by downregulating MIR17HG expression.

SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment.

Despite significant advancements in the field of oncology, cancers still pose one of the greatest challenges of modern healthcare. Given the cytoskeleton's pivotal role in regulating mechanisms critical to cancer development, further studies of the cytoskeletal elements could yield new practical applications. Septins represent a group of relatively well-conserved GTP-binding proteins that constitute the fourth component of the cytoskeleton. Septin 9 (SEPT9) has been linked to a diverse spectrum of malignancies and appears to be the most notable septin member in that category. SEPT9 constitutes a biomarker of colorectal cancer (CRC) and has been positively correlated with a high clinical stage in breast cancer, cervical cancer, and head and neck squamous cell carcinoma. SEPT9_i1 represents the most extensively studied isoform of SEPT9, which substantially contributes to carcinogenesis, metastasis, and treatment resistance. Nevertheless, the mechanistic basis of SEPT9_i1 oncogenicity remains to be fully elucidated. In this review, we highlight SEPT9's and SEPT9_i1's structures and interactions with Hypoxia Inducible Factor α (HIF-1 α) and C-Jun N-Terminal Kinase (JNK), as well as discuss SEPT9_i1's contribution to aneuploidy, cell invasiveness, and taxane resistance-key phenomena in the progression of malignancies. Finally, we emphasize forchlorfenuron and other septin inhibitors as potential chemotherapeutics and migrastatics.

Prognostic value of the postoperative carcinoembryonic antigen level in colorectal cancer: A meta-analysis.

Carcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta-analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator. We conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS)/recurrence-free survival (RFS), were analyzed using a fixed-effects or random-effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. This meta-analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36-3.62, and p<0.000), DFS (HR: 2.81, 95% CI: 2.01-3.94, and p<0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75-3.62, p<0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups. When CEA levels are found to be elevated during postoperative follow-up, more active intervention measures should be implemented to further improve the patient's survival outcomes.

The Effect of C-X-C Motif Chemokine Ligand 12 in Colorectal Cancer Associated with Chemoresistance and Radioresistance as Well as Stemness.

We aimed to explore the role of C-X-C motif chemokine ligand 12 (CXCL12) and cytokinecytokine receptor interaction signaling pathway in the radiotherapy and chemotherapy resistance as well as cell stemness in colorectal cancer (CRC). Bioinformatics analysis was used to identify the differentially expressed mRNAs and signal pathways closely related to differentially expressed mRNAs have also been analyzed in March 2022 at the Jinhua Central Hospital, China. Then, the expression of CXCL12 was detected by qRT-PCR in colorectal cancer cells and testing the effects of transfecting CXCL12 into different CRC-derived cell lines. The effects of CXCL12 on cell proliferation were evaluated by chemosensitivity assay and radiation sensitivity assay. Bioinformatics analysis of DEGs found a total of 2429 differentially expressed genes, THBS3 and CXCL12 genes are two abnormally highly expressed genes in the CRC. KEGG analysis showed the correlative signaling pathway, cytokine-cytokine receptor interaction, which is related to cell stemness. Furthermore, the expression of CXCL12 in CRC cells was detected and an increasing trend was obtained in CRC cells. In addition, the chemosensitivity and radiotherapy tolerance were elevated after transfected with CXCL12. CXCL12 could be a potential promote biomarkers in CRC and also promote the chemosensitivity and radiotherapy tolerance.

Tumorspheres as In Vitro Model for Identifying Predictive Chemoresistance and Tumor Aggressiveness Biomarkers in Breast and Colorectal Cancer.

Chemoresistance remains a major challenge in the treatment of breast and colorectal cancer. For this reason, finding reliable predictive biomarkers of response to chemotherapy has become a significant research focus in recent years. However, validating in vitro results may be problematic due to the outcome heterogeneity. In this study, we evaluate the use of tumorspheres as an in vitro model for validating biomarkers of chemoresistance in breast and colorectal cancer. Our investigation highlights the crucial role of inflammation-related pathways in modulating the response to chemotherapy. Using in silico approaches, we identified specific markers elevated in responders versus non-responders patients. These markers were consistently higher in three-dimensional (3D) tumorsphere models compared to traditional adherent cell culture models. Furthermore, the number of tumorspheres from breast and colorectal cancer cells increased in response to cisplatin and oxaliplatin treatment, respectively, whereas cell viability decreased in adherent cell culture. This differential response underscores the importance of the 3D tumorsphere model in mimicking the tumor microenvironment more accurately than adherent cell culture. The enhanced chemoresistance observed in the 3D tumorspheres model and their correlation of data with the in silico study suggest that 3D culture models are a better option to approach the in vivo model and also to validate in silico data. Our findings indicate that tumorspheres are an ideal model for validating chemoresistance biomarkers and exploring the interplay between inflammation and chemoresistance in breast and colon cancer.

Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer

Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC. This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes. Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.

Prognostic value of post-operative iron biomarkers in colorectal cancer: population-based patient cohort

BackgroundPost-operative anaemia is linked to iron deficiency. We investigated the prognostic value of post-operative iron biomarkers in colorectal cancer (CRC).MethodsFerritin, transferrin, iron, and transferrin saturation (TS%) were measured from blood collected at a single time-point post-surgery in 2769 CRC patients. Associations between iron biomarkers with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox regression with hazard ratios (HR), stratified by post-operative time of blood collection (<1-month/≥1-month).ResultsAfter a median follow-up of 9.5 years, 52.6% of patients had died. For iron biomarkers assessed <1-month post-surgery, higher compared to normal TS% was associated with shorter CSS (HR [95% CI] = 2.36 [1.25–4.46]), and higher iron levels with better OS (upper vs. median tertile: HR [95% CI] = 0.79 [0.65–0.97]). When assessed ≥1-month post-surgery, elevated ferritin was associated with poor CSS (high vs. normal: HR [95% CI] = 1.44 [1.10–1.87]), and low TS% with worse CSS (low vs. normal: HR [95% CI] = 1.60 [1.24–2.06]). Similar but weaker associations were observed for OS.ConclusionMonitoring of serum ferritin and TS% beyond 1-month post-surgery may be relevant for risk stratification of patients with operable CRC. Future studies should validate our findings.

Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route.

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.

The prognostic value of programmed death-ligand 1 (PD-L1) expression in resected colorectal cancer without neoadjuvant therapy - differences between antibody clones and cell types

BackgroundProgrammed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones.MethodsPatients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively.ResultsPD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis.ConclusionsThe prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.

Texture analysis of CT colonography to develop a novel imaging biomarker for the management of colorectal cancer

AbstractBackgroundRecent studies have focused on evaluating the biomarker value of textural features in radiological images. Our study investigated whether or not a texture analysis of computed tomographic colonography (CTC) images could be a novel biomarker for colorectal cancer (CRC).MethodsThis retrospective study investigated 263 patients with CRC who underwent contrast‐enhanced CTC (CE‐CTC) before curative surgery between January 2014 and December 2017. Multiple texture analyses (fractal, histogram, and gray‐level co‐occurrence matrix [GLCM] texture analyses) were applied to CE‐CTC (portal‐venous phase), and fractal dimension (FD), skewness, kurtosis, entropy, and GLCM texture parameters, including GLCM‐correlation, GLCM‐autocorrelation, GLCM‐entropy, and GLCM‐homogeneity, of the tumor were calculated. These texture parameters were compared with pathological factors (tumor depth, lymph node metastasis, vascular invasion, and lymphatic invasion) and overall survival (OS).ResultsTumor depth was significantly associated with FD, kurtosis, entropy, GLCM‐correlation, GLCM‐autocorrelation, GLCM‐entropy, and GLCM‐homogeneity (p = 0.001, 0.001, 0.001, 0.001, 0.018, 0.008, and 0.001, respectively); lymph node metastasis was associated with GLCM‐homogeneity (p = 0.004); lymphatic invasion was associated with GLCM‐correlation and GLCM‐homogeneity (p = 0.001 and 0.012, respectively); and venous invasion was associated with FD, entropy, GLCM‐correlation, GLCM‐autocorrelation, and GLCM‐entropy of the tumor (p = 0.001, 0.033, 0.021, 0.046, respectively). In the Kaplan–Meier analysis, patients with high GLCM‐correlation tumors or high GLCM‐homogeneity tumors showed a significantly worse OS than others (p = 0.001 and 0.04, respectively). Multivariate analyses showed that the GLCM correlation was an independent prognostic factor for the OS (p = 0.021).ConclusionCE‐CTC‐derived texture parameters may be clinically useful biomarkers for managing CRC patients.

IFITM10 Enhance Tumor Angiogenesis and Promotes Cancer Progression through STAT3 Activation.

Humankind have been struggling with colorectal cancer (CRC) for long period with its rapid progression and invasive metastasis. By hyperactivating IL-6/STAT3 signaling, CRC facilitates the capacity of angiogenesis to plunder massive nutrients and develops gradually under harsh condition. The Cancer Genome Atlas database was analyzed for acquiring interferon-γ inducible protein 10 (IFITM10) expression levels and their correlation with clinical outcomes. The cell angiogenic ability were assessed by Cell Counting Kit-8 (CCK-8) and tube formation assay. Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA) assay were using to assess potential mechanism. In our study, we find that IFITM10 is upregulated in CRC and is positively related with tumor angiogenesis. We also find that IFITM inhibition decreased STAT3 phosphorylation level and IFITM10-mediated angiogenesis depends on STAT3 activation. Furthermore, our data suggests that IFITM10 may be a key prognostic biomarker in colorectal cancer. Together, our study suggests that IFITM10 enhance angiogenesis through STAT3 activation during CRC progression, which highlighting its potency as a therapeutic target for colorectal cancer.

Converging deep learning and human-observed tumor-adipocyte interaction as a biomarker in colorectal cancer

BackgroundTumor-Adipose-Feature (TAF) as well as SARIFA (Stroma AReactive Invasion Front Areas) are two histologic features/biomarkers linking tumor-associated adipocytes to poor outcomes in colorectal cancer (CRC) patients. Whereas TAF was identified by deep learning (DL) algorithms, SARIFA was established as a human-observed histopathologic biomarker.MethodsTo study the overlap between TAF and SARIFA, we performed a systematic pathological review of TAF based on all published image tiles. Additionally, we analyzed the presence/absence of TAF in SARIFA-negative CRC cases to elucidate the biologic and prognostic role of a direct tumor-adipocyte contact. TCGA-CRC gene expression data is investigated to assess the association of FABP4 (fatty-acid binding protein 4) and CD36 (fatty-acid translocase) with both TAF and CRC prognosis.ResultsBy investigating the TAF/SARIFA overlap, we show that many TAF patches correspond to the recently described SARIFA-phenomenon. Even though there is a pronounced morphological and biological overlap, there are differences in the concepts. The presence of TAF in SARIFA-negative CRCs is not associated with poor outcomes in this cohort, potentially highlighting the importance of a direct tumor-adipocyte interaction. Upregulation of FABP4 and CD36 gene expression seem both linked to a poor prognosis in CRC.ConclusionsBy proving the substantial overlap between human-observed SARIFA and DL-based TAF as morphologic biomarkers, we demonstrate that linking DL-based image features to independently developed histopathologic biomarkers is a promising tool in the identification of clinically and biologically meaningful biomarkers. Adipocyte-tumor-cell interactions seem to be crucial in CRC, which should be considered as biomarkers for further investigations.

Identification of Novel Target DCTPP1 for Colorectal Cancer Therapy with the Natural Small-molecule Inhibitors Regulating Metabolic Reprogramming.

Colorectal cancer (CRC) is one of the most common malignant tumours. Identification of new effective drug targets for CRC and exploration of bioactive small-molecules are clinically urgent. The human dCTP pyrophosphatase 1 (DCTPP1) is a newly identified pyrophosphatase regulating the cellular nucleotide pool but remains unexplored as potential target for CRC treatment. Here, twelve unprecedented chemical architectures terpene-nonadride heterodimers (1-12) and their monomers (13-20) were isolated from endophyte Bipolaris victoriae S27. Compounds 1-12 represented the first example of terpene-nonadride heterodimers, in which nonadride monomers of 1 and 2 were also first example of 5/6 bicyclic nonadrides. A series of assays showed that 2 could repress proliferation and induce cell cycle arrest, apoptotic and autophagic CRC cell death in vitro and in vivo. Clinical cancer samples data revealed that DCTPP1 was a novel target associated with poor survival in CRC. DCTPP1 was also identified as a new target protein of 2. Mechanistically, compound 2 bound to DCTPP1, inhibited its enzymatic activity, intervened with amino acid metabolic reprogramming, and exerted anti-CRC activity. Our study demonstrates that DCTPP1 was a novel potential biomarker and therapeutic target in CRC, and 2 was the first natural anti-CRC drug candidate targeting DCTPP1.

Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer.

Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific. Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics. Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053). The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.

BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer

BackgroundDespite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. MethodsUsing quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. ResultsMAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. ConclusionsThis study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.

Recent Technologies towards Diagnostic and Therapeutic Applications of Circulating Nucleic Acids in Colorectal Cancers.

Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation.

Development of an Impedance and QCM-Based Electrochemical Biosensor for the Detection of Colon Cancer-Secreted Protein-2 (CCSP-2), a Potential Colorectal Cancer Biomarker

Research on colon cancer diagnosis is advancing due to the application of electrochemical biosensors. Early screening can significantly reduce the overall mortality rate from colorectal cancer (CRC). Colon cancer-secreted protein-2 (CCSP-2) is specifically overexpressed and secreted by cancerous cells and adenomas found in the colon. Utilizing a cost-effective and non-invasive electrochemical immunosensor for CCSP-2 detection can aid in the early diagnosis of disease recurrences in individuals with colon cancer. In this work, we designed a simplified electrochemical immunosensor consisting of a functionalized gold (Au) electrode using cysteine-modified recombinant protein G (RPGCys) to immobilize the CCSP-2 antibody. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) have been used to analyze the electrochemical response caused by the binding between the target CCSP-2 and anti-CCSP-2, and there are significant changes observed for charge transfer resistance (Rct) in EIS and current density in CV. The quantification of mass changes attributed to binding events within the sensor will be determined through the application of quartz crystal microbalance (QCM). Angle-resolved X-ray photoelectron spectroscopy (ARXPS) and atomic force microscopy (AFM) will be used for the characterization of the sensor surface. The sensor's sensitivity and specificity will be assessed through the determination of the limit of detection and comprehensive testing of the probe with varied proteins and cell lines sourced from both cancerous and non-cancerous patient samples. This electrochemical probe is expected to enable the rapid and direct detection of early-stage colorectal cancer.

Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.

Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors have significantly improved patient outcomes, their effectiveness is mostly limited to tumors with microsatellite instability (MSI-H/dMMR) or an increased tumor mutational burden, which comprise 10% of cases. Advancing personalized medicine in CRC hinges on identifying predictive biomarkers to guide treatment decisions. This comprehensive review examines established tissue markers such as KRAS and HER2, highlighting their roles in resistance to anti-EGFR agents and discussing advances in targeted therapies for these markers. Additionally, this review summarizes encouraging data on promising therapeutic targets and highlights the clinical utility of liquid biopsies. By synthesizing current evidence and identifying knowledge gaps, this review provides clinicians and researchers with a contemporary understanding of the biomarker landscape in CRC. Finally, the review examines future directions and challenges in translating promising biomarkers into clinical practice, with the goal of enhancing personalized medicine approaches for colorectal cancer patients.