Diagnostic Biomarker For Colorectal Cancer Research Articles

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.

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.

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.

Gut Microbiota Signatures in Colorectal Cancer as a Potential Diagnostic Biomarker in the Future: A Systematic Review.

The gut microbiota has acquired significant attention in recent years for its potential as a diagnostic biomarker for colorectal cancer (CRC). In this literature review, we looked at the studies exploring alterations in gut microbiota composition associated with CRC, the potential mechanisms linking gut dysbiosis to CRC development, and the diagnostic approaches utilizing gut microbiota analysis. Our research has led to the conclusion that individuals with CRC often display alterations in their gut microbiota composition compared to healthy individuals. These alterations can include changes in the diversity, abundance, and type of bacteria present in the gut. While the use of gut microbiota as a diagnostic biomarker for CRC holds promise, further research is needed to validate its effectiveness and standardize testing protocols. Additionally, considerations such as variability in the microbiota composition among individuals and potential factors must be addressed before microbiota-based tests can be widely implemented in clinical practice.

The roles and mechanisms of APOL1 in the development of colorectal cancer.

Research has demonstrated that apolipoprotein L1 (APOL1) has a role in the emergence and progression of a number of malignant cancers. It is unclear, however, how APOL1 functions in colorectal cancer (CRC). In this study, we examined the possible molecular processes underlying APOL1's biological role in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to identify APOL1 expression in patients with CRC and the cell line of cancer tissue. Following transfection of human colon carcinoma cells (HCT116) and human colon adenocarcinoma cells (SW1116) with sh-APOL1, the effects of APOL1 on the biological behavior of CRC cell lines were examined. In nude mice, the effect of APOL1 on tumor growth was noted. The protein interaction between APOL1 and RUNX1 was detected via coimmunoprecipitation. The expression of relevant proteins and cell biological behaviors were examined to confirm the APOL1-RUNX1 pathway in CRC cell lines. The CRC tissues and cells exhibited elevated expression of APOL1. HCT116 and SW1116 cells' proliferation, migration, and invasion were suppressed by sh-APOL1, and sh-APOL1 also increased the expression of E-cadherin and decreased the expression of RUNX1, cyclin D1, β-catenin, N-cadherin, and vimentin. APOL1 bound to the RUNX1 protein and regulated its protein levels. The counteractive effect of sh-APOL1 epithelial-mesenchymal transition (EMT), proliferation, migration, and invasion of CRC cells was counteracted by the overexpression of RUNX1. By silencing APOL1, the Wnt-β-catenin pathway was able to restrain EMT and regulate the biological behavior processes in CRC cells. APOL1 has potential as a diagnostic biomarker for CRC. By preventing the Wnt-β-catenin pathway from being activated, the sh-APOL1-binding protein RUNX1 inhibited the EMT and biological behavior of CRC cells.

Detection of caudal type homeobox 1 (CDX1) gene methylated DNA, as a stool-based diagnostic biomarker in colorectal cancer

Detection of caudal type homeobox 1 (CDX1) gene methylated DNA, as a stool-based diagnostic biomarker in colorectal cancer

Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study.

The absence of non-invasive biomarkers for the early diagnosis of colorectal cancer (CRC) has contributed to poor prognosis. Extracellular vesicles (EVs) have emerged as promising candidates for cancer monitoring using liquid biopsy. However, the complexity of EVs isolation procedures and the absence of clear targets for detecting serum-derived EVs have hindered the clinical application of EVs in early CRC diagnosis. In the discovery phase, we conducted a comprehensive 4D-DIA proteomic analysis of serum-derived EVs samples from 37 individuals, performing an initial screening of EVs surface proteins. In the technical validation phase, we developed an extraction-free CRC-EVArray microarray to assess the expression of these potential EVs surface proteins in a multi-centre study comprising 404 individuals. In the application phase, the authors evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms. Through 4D-DIA proteomic analysis, the authors identified seven potential EVs surface proteins showing significantly differential expression in CRC patients compared to healthy controls. Utilizing our developed high-throughput CRC-EVArray microarray, we further confirmed the differential expression of three EVs surface proteins, FIBG, PDGF-β and TGF-β, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an area under the curve (AUC) of 0.882 in the train set and 0.937 in the test set. Additionally, we predicted the functions and potential origins of these EVs-derived proteins through a series of multi-omics approaches. Our systematic exploration of surface protein expression profiles on serum-derived EVs has identified FIBG, PDGF-β, and TGF-β as novel diagnostic biomarkers for CRC. The development of CRC-EVArray diagnostic model based on these findings provided an effective tool for the large-scale CRC screening, thus facilitating its translation into clinical practice.

A transcribed ultraconserved noncoding RNA, uc.285+, promotes colorectal cancer proliferation through dual targeting of CDC42 by directly binding mRNA and protein

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.

N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer

BackgroundN6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC.MethodsWe collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model.ResultsPB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased.ConclusionsPB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

Upregulation of Long Noncoding RNA PCAT1 in Iranian Patients with Colorectal Cancer and Its Performance as a Potential Diagnostic Biomarker.

Background: Long noncoding RNAs (lncRNAs) as critical molecules play an essential role in the development of cancers. In colorectal cancer (CRC), various lncRNAs are related to cell proliferation, apoptosis, migration, and invasion. LncRNA prostate cancer-associated transcript 1 (PCAT-1), as an oncogenic factor, is a diagnostic biomarker that regulates cell proliferation, migration, invasion, and apoptosis. Methods: This study evaluated the relationship between PCAT-1, CRC occurrence, and pathological features of Iranian patients. The studied samples included 100 colorectal tumor tissues and 100 adjacent healthy tissues of Iranian CRC patients. RNAs were extracted from cancerous and noncancerous tissues to synthesize complementary DNA. The expression level of PCAT-1 was assessed using the real-time PCR method, and the data analysis was assessed using SPSS software. Results: In this study, expression level of PCAT-1 in tumor tissue was significantly increased in Iranian patients, and pathological studies of the patients had no significant relationship with the PCAT-1 expression profile. Conclusion: Our results suggested that the high expression of PCAT-1 resulted in the occurrence of colorectal tumor tissues in Iranian patients, which can be considered a diagnostic biomarker in CRC.

Evaluation of tumor-educated platelet long non-coding RNAs (lncRNAs) as potential diagnostic biomarkers for colorectal cancer.

Cancer-derived circulating components are increasingly considered as candidate sources for non-invasive diagnostic biomarkers. This study aimed to investigate the expression of tumor-educated platelet (TEP) long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) patients and determine whether it could be served as a potential tool for CRC diagnosis. Relative quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of three cancer-related platelet-derived lncRNAs CCAT1, HOTTIP, and XIST in 75 CRC patients and 42 healthy controls. Quantitative data were analyzed by SPSS (IBM Corp., Armonk, NY, USA) for comparison of cancer and non-cancer individuals. The receiver operating characteristic (ROC) curve analysis was further performed to assess the diagnostic values of lncRNAs within the CRC patients. The expression levels of lncRNAs colon cancer associated transcript 1 (CCAT1) ( P = 0.006) and HOXA transcript at the distal tip (HOTTIP) ( P = 0.049), but not X-inactive specific transcript (XIST) ( P = 0.12), were significantly upregulated in CRC patients compared to healthy individuals. However, there were no significant correlations between platelet lncRNAs and clinicopathological characteristics, including sex, age, tumor location, differentiation, and size (all at P > 0.05). The area under the ROC curve (AUC) of the lncRNA CCAT1 was 0.61 (sensitivity, 71%; specificity, 50%). TEP lncRNA CCAT1 is detectable in the circulation of CRC patients and could be considered as a potential diagnostic biomarker.

Investigation of the potential of miRNA candidates as non-invasive biomarkers for the diagnosis and follow-up of colorectal cancer

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide, and despite advances in treatment, molecular biomarkers are needed for both early diagnosis and prognosis monitoring. It is known that microRNAs (miRNA), one of the epigenetic mechanisms, are effective in the initiation and development of cancer by regulating the activity of tumor suppressors and/or oncogenes. In this study, the potential of the molecules let-7, miRNA125b, and miRNA30a, which are known to play a role in cellular processes, as biomarkers for colorectal cancer and their molecular mechanisms were investigated in this model. The aim was to evaluate the diagnostic, prognostic, and predictive utility of the target miRNAs in colorectal cancer patients. Material and methodsThe expression changes of miRNAs let-7, miRNA125b, and miRNA30a were investigated by miRNAs isolation and cDNA synthesis from the serum samples of 60 patients diagnosed with CRC or from the serum samples of 20 healthy individuals. The calculation was performed using the quantitative real-time polymerase chain reaction method to determine the expression level. The results were compared with clinical parameters. ResultAn 8-fold decrease in the expression of let-7 and miRNA125b and a 60-fold decrease in the expression of miRNA30a were found in the serum samples of patients diagnosed with colorectal cancer (CRC) compared to the healthy group. A decrease in let-7 was observed in 53.3%, miRNA125b in 58.3%, and miRNA30a in 55% of patients. A significant correlation was found between the reduced expression status and the stage, lymph nodes, local recurrence, and metastasis (p < 0.05). The ROC analysis showed that the miRNA30a level could be a diagnostic biomarker for CRC (p < 0.001). No significant impact of target miRNA expression changes on overall disease survival was observed. ConclusionIt is thought that the target miRNA30a can be used for early diagnosis and screening and that the target miRNA let-7, miRNA125b, and miRNA30a can be used as non-invasive biomarkers for disease follow-up, with larger patient studies being conducted on CRC patients.

Investigation of GNB1 derivative circular RNAs hsa_circ_0009361 and hsa_circ_0009362 expressions in colorectal cancer patients: potential new diagnostic factors.

We aim to investigate the relationship between hsa_circ_0009361 plus hsa_circ_0009362 expression levels and the clinicopathological features of colorectal cancer (CRC) patients. Circular RNAs (circRNAs) are implicated in the progression and development of CRC. CircRNAs have been recognized as diagnostic and prognostic biomarkers, opening up a new window to comprehend the molecular basis of CRC. Given the significance of circRNAs and the G protein subunit b1 (GNB1) gene in malignancies, the goal of the current investigation was to determine the expression levels of GNB1 derivative circular RNAs circGNB1 (hsa_circ_0009361 and hsa_circ_0009362) in CRC and adjacent control tissues. The expression levels of the GNB1 derivative circular RNAs (hsa_circ_0009361 and hsa_circ_0009362) were evaluated using the quantitative real-time PCR (qRT-PCR) method in 45 CRC tissues and adjacent control tissues. Furthermore, we analyzed the diagnostic power of the mentioned circRNAs by plotting the receiver operating characteristic (ROC) curve. The association between the expression levels of hsa_circ_0009361 and hsa_circ_0009362 was evaluated using correlation analysis. Our results revealed that the expression levels of hsa_circ_0009361 and hsa_circ_0009362 were significantly down-regulated in CRC tissues compared to the adjacent control group. Analysis of patients' clinicopathological features indicated that expressions of hsa_circ_0009361 and hsa_circ_0009362 were differently related to lymph vascular invasion (P<0.001). ROC curve results showed that these circRNAs are good candidate diagnostic biomarkers in CRCs. Pearson's correlation test revealed a positive correlation between hsa_circ_0009361 and hsa_circ_0009362 expression levels (P<0.0001). These results demonstrated that hsa_circ_0009361 and hsa_circ_0009362 expression levels may be used as possible diagnostic biomarkers for CRC.

ADAR-mediated RNA editing regulates PVR immune checkpoint in colorectal cancer

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3′-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC.

Evaluating Cytokines and Antimicrobial Peptides as Diagnostic Biomarkers in Colorectal Cancer and Adenomatous Polyps

Evaluating Cytokines and Antimicrobial Peptides as Diagnostic Biomarkers in Colorectal Cancer and Adenomatous Polyps

Novel PBMC LncRNA signatures as diagnostic biomarkers for colorectal cancer

The expression of long non-coding RNAs (LncRNAs) in peripheral blood mononuclear cell (PBMC) and its clinical relevance in colorectal cancer (CRC) remains largely uncharacterized. To address these gaps, we investigated the expression profiles of lncRNAs in PBMC from CRC and healthy controls (HC) by RNA sequencing. The expression level of differentially expressed lncRNAs (DElncRNAs) were evaluated by quantitative PCR in PBMC samples from CRC patients and HC. A total of 447 DElncRNAs were identified, with 178 elevated lncRNAs and 269 decreased lncRNAs in PBMC from CRC patients as compared with that from HC. RT-PCR results supported a significant elevation of NEAT1:11, lnc-PDZD8–1:5 and LINC00910:16 in 98 CRC patients and 82 HC. The clinical implication of NEAT1:11, lnc-PDZD8–1:5 and LINC00910:16 as CRC diagnostic biomarker were determined by receiver operating characteristic (ROC) curve, showing sensitivity 74.5% and specificity 84.5% for joint detection the three lncRNAs. Notably, NEAT1:11 was closely related with the size and extent of primary tumor, with higher relative expression of NEAT1:11 in higher T stage (P = 0.0047). Moreover, NEAT1:11 was related with grade (P = 0.012). Collectively, PBMC from patients with CRC show significantly variable expression profiles of lncRNAs, and detection of these differential expression lncRNAs may provide useful information for basic and clinical research.

Oncogene SCARNA12 as a potential diagnostic biomarker for colorectal cancer

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, and represents a severe threat to the life and health of individuals. Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) as critical regulatory gene in cancer development. Small Cajal body-specific RNAs (scaRNAs), a subtype of snoRNAs, are named for their subcellular localization within Cajal bodies. SCARNA12, which located at the intronic region of PHB2 in chromosome 12p13.31 with 270 nucleotides (nt) in length. It has been reported function as a diagnostic marker for cervical cancer. However, its biological functions and molecular mechanisms in CRC have yet to be elucidated. In this study, bioinformatics analysis revealed that SCARNA12 was highly expressed in CRC and positively correlated with poor prognosis in CRC patients. Additionally, SCARNA12 showed upregulated expression in CRC cell lines and clinical CRC tissue samples. Moreover, SCARNA12 overexpression in SW620 cells accelerated cell proliferation, suppressed the apoptosis rate, and enhanced tumorigenesis in vivo. The knockdown of SCARNA12 expression in HCT116 and HT29 cells resulted in contrasting effects. The functioning of SCARNA12 is mechanically independent of its host gene PHB2. Notably, the overexpression of SCARNA12 activated PI3K/AKT pathway in SW620 cells, and the malignancy degree of CRC cells was attenuated after treatment with MK2206 (a specific AKT inhibitor). Our findings demonstrated that SCARNA12 plays an oncogenic role in CRC progression and can be used as a potential diagnostic biomarker for CRC.

Peptostreptococcus anaerobius is a potential diagnostic biomarker of colorectal cancer

Peptostreptococcus anaerobius is a potential diagnostic biomarker of colorectal cancer

Metagenomic analysis reveals gut plasmids as diagnosis markers for colorectal cancer.

Colorectal cancer (CRC) is linked to distinct gut microbiome patterns. The efficacy of gut bacteria as diagnostic biomarkers for CRC has been confirmed. Despite the potential to influence microbiome physiology and evolution, the set of plasmids in the gut microbiome remains understudied. We investigated the essential features of gut plasmid using metagenomic data of 1,242 samples from eight distinct geographic cohorts. We identified 198 plasmid-related sequences that differed in abundance between CRC patients and controls and screened 21 markers for the CRC diagnosis model. We utilize these plasmid markers combined with bacteria to construct a random forest classifier model to diagnose CRC. The plasmid markers were able to distinguish between the CRC patients and controls [mean area under the receiver operating characteristic curve (AUC = 0.70)] and maintained accuracy in two independent cohorts. In comparison to the bacteria-only model, the performance of the composite panel created by combining plasmid and bacteria features was significantly improved in all training cohorts (mean AUCcomposite = 0.804 and mean AUCbacteria = 0.787) and maintained high accuracy in all independent cohorts (mean AUCcomposite = 0.839 and mean AUCbacteria = 0.821). In comparison to controls, we found that the bacteria-plasmid correlation strength was weaker in CRC patients. Additionally, the KEGG orthology (KO) genes in plasmids that are independent of bacteria or plasmids significantly correlated with CRC. We identified plasmid features associated with CRC and showed how plasmid and bacterial markers could be combined to further enhance CRC diagnosis accuracy.

Evaluation of C–reactive protein and fibrinogen in comparison to CEA and CA72–4 as diagnostic biomarkers for colorectal cancer

Carcinoembryonic antigen (CEA) and carbohydrate antigen 72–4 (CA72–4) are commonly used markers for colorectal cancer (CRC) in clinical applications. However, low positivity rate and sensitivity limits their clinical effectiveness. In this study, we explored the potential of C–reactive protein (CRP) and fibrinogen to improve the diagnostic efficiency of traditional biomarkers of CRC. The concentrations of CRP and fibrinogen in plasma were significantly higher in CRC patients compared with benign or healthy controls. The area under the ROC curves (AUCs) showed that the diagnostic efficacy of CRP and fibrinogen was 0.745 (95% CI: 0.712–0.779) and 0.699 (95% CI: 0.663–0.734), respectively. AUC increased to 0.750 (95% CI: 0.716–0.784) when CRP and fibrinogen were combined. It also further improved to 0.889 (95% CI: 0.866–0.913) when CRP and fibrinogen were integrated with CEA and CA72–4. Moreover, this combination increased the maximum area under AUC to 0.857 (95% CI: 0.830–0.883), which effective differentiated CRC from benign disease. Overall, this study found that CRP and fibrinogen were highly expressed in the plasma of CRC patients, suggesting their potential to improve the diagnostic efficiency of traditional biomarkers of CRC.