Diagnostic Value For Colorectal Cancer Research Articles

Meta-analysis on the Diagnostic Value of SDC2 Methylation in Colorectal Cancer Screening Among Chinese

To systematically evaluate the diagnostic value of syndecan-2 (SDC2) gene methylation status in the detection of Colorectal cancer (CRC) and advanced adenomas (AA) through meta-analysis. Databases including PubMed, Web of Science were searched from 2020 to June 14, 2024. Relevant studies were selected based on predefined inclusion and exclusion criteria. The true positive (TP), false positive (FP), false negative (FN), and true negative (TN) results were calculated for each study. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A bivariate meta-analysis model was used to pool the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR), and a summary receiver operating characteristic (SROC) curve was constructed. Spearman’s correlation coefficient, Cochran-Q test, and I² test were used to evaluate heterogeneity. Sensitivity analysis was performed to explore the potential sources of heterogeneity. 24 literatures were included for meta-analysis. The pooled sensitivity was 0.77 for CRC and 0.52 for AA, and the pooled specificity was 0.93 for CRC and 0.91 for AA. The pooled PLR was 10.63 for CRC and 5.57 for AA, and the pooled NLR was 0.25 for CRC and 0.53 for AA. The DOR was 43.21 for CRC and 10.47 for AA. The SROC AUC was 0.91 for CRC and 0.83 for AA. The methylation level of the SDC2 gene in stool samples has significant diagnostic value for colorectal cancer and is considered an ideal biomarker for the early detection of this disease.

Discovery and validation of colorectal cancer tissue-specific methylation markers: a dual-center retrospective cohort study

Background and purposeEarly detection, diagnosis, and treatment of colorectal cancer and its precancerous lesions can significantly improve patients’ survival rates. The purpose of this research is to identify methylation markers specific to colorectal cancer tissues and validate their diagnostic capability in colorectal cancer and precancerous changes by measuring the level of DNA methylation in stool samples.MethodWe analyzed samples from six cancer tissues and adjacent normal tissues and fecal samples from 758 participants, including 62 patients with interfering diseases. Bioinformatics databases were used to screen for candidate biomarkers for CRC, and quantitative methylation-specific PCR methods were applied for identification. The methylation levels of the candidate biomarkers in fecal and tissue samples were measured. Logistic regression and random forest models were built and validated using fecal sample data from one of the centers, and the independent or combined diagnostic value of the candidate biomarkers in fecal samples for CRC and precancerous lesions was analyzed. Finally, the diagnostic capability and stability of the model were validated at another medical center.ResultsThis study identified two colorectal cancer CpG sites with tissue specificity. These two biomarkers have certain diagnostic power when used individually, but their diagnostic value for colorectal cancer and colorectal adenoma is more significant when they are used in combination.ConclusionThe results indicate that a DNA methylation biomarker combined diagnostic model based on two CpG sites, cg13096260 and cg12587766, has the potential for screening and diagnosing precancerous lesions and colorectal cancer. Additionally, compared to traditional diagnostic models, machine learning algorithms perform better but may yield more false-positive results, necessitating further investigation.

Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis

BackgroundDespite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening.MethodA comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092.ResultsFrom an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity.ConclusionsAmong the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Value of combined serum CEA, CA72-4, and CA19-9 marker detection in diagnosis of colorectal cancer.

The aim of this study was to examine whether the combination of serum tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA]72-4, CA19-9) improves sensitivity and accuracy in the diagnosis of colorectal cancer and precancerous lesion tubular adenoma. An automatic electrochemiluminescence immunoassay with matched kits (ECLIA) was performed on a Roche Cobas e411 analyzer to determine the levels of serum CEA, CA72-4, and CA19-9 in 35 patients with early colorectal cancer, 87 patients with tubular adenoma, and 58healthy people undergoing colonoscopy after positive fecal immunochemical test (FIT) in a colorectal cancer screening program 2021 January to April. The values of these three tumor markers in the diagnosis of colorectal cancer and tubular adenoma were analyzed. 180 patients (92 female and 88 male) were included into the study. We compared serum CEA, CA72-4 and CA19-9 markers among 3 groups: healthy people (mean age 64,0 ±8,6), patients with tubular adenoma (mean age 62,7 ± 6,4) and colorectal cancer (mean age 59,2 ±6,2). The levels of serum CEA, CA72-4, and CA19-9 were higher in the colorectal cancer group than in the tubular adenoma group and healthy subjects, and these differences were significant (p < 0.05). The combination of CEA, CA72-4, and CA19-9had a higher diagnostic value for colorectal cancer compared to single markers, and the positive detection rate was 54.3%. The diagnostic power when using all three markers was the best, and applied for colorectal cancer and tubular adenoma. The combination of CA72-4, CEA, and CA19-9 markers increases the sensitivity and accuracy in the diagnosis of colorectal cancer and can thus be considered an important tool for early colorectal diagnosis.

Comparative detection of syndecan-2 methylation in preoperative and postoperative stool DNA in patients with colorectal cancer.

Early detection of colorectal cancer (CRC) is essential to reduce cancer-related morbidity and mortality. Stool DNA (sDNA) testing is an emerging method for early CRC detection. Syndecan-2 (SDC2) methylation is a potential biomarker for the sDNA testing. Aberrant DNA methylation is an early epigenetic event during tumorigenesis and can occur in the normal colonic mucosa during aging, which can compromise the sDNA test results. To determine whether methylated SDC2 in sDNA normalizes after surgical resection of CRC. In this prospective study, we enrolled 151 patients with CRC who underwent curative surgical resection between September 2016 and May 2020. Preoperative stool samples were collected from 123 patients and postoperative samples were collected from 122 patients. A total of 104 samples were collected from both preoperative and postoperative patients. Aberrant promoter methylation of SDC2 in sDNA was assessed using linear target enrichment quantitative methylation-specific real-time polymerase chain reaction. Clinicopathological parameters were analyzed using the results of SDC2 methylation. Detection rates of SDC2 methylation in the preoperative and postoperative stool samples were 88.6% and 19.7%, respectively. Large tumor size (3 cm, P = 0.019) and advanced T stage (T3-T4, P = 0.033) were positively associated with the detection rate of SDC2 methylation before surgery. Female sex was associated with false positives after surgery (P = 0.030). Cycle threshold (CT) values were significantly decreased postoperatively compared with preoperative values (P < 0.001). The postoperative negative conversion rate for preoperatively methylated SDC2 was 79.3% (73/92). Our results suggested that the SDC2 methylation test for sDNA has acceptable sensitivity and specificity. However, small size and early T stage tumors are associated with a low detection rate of SDC2 methylation. As the cycle threshold values significantly decreased after surgery, SDC2 methylation test for sDNA might have a diagnostic value for CRC.

PRELIMINARY RESULTS OF lncRNAs AS BIOMARKERS FOR COLORECTAL CANCER DIAGNOSIS

Abstract Introduction lncRNAs are strands larger than 200 nucleotides that do not encode proteins. They have regulatory functions in cell proliferation, apoptosis and migration. They are stable over a long period and may have diagnostic value in colorectal cancer (CRC). Their availability as effective biomarkers for CRC screening would represent a substantial advance, as tests could be performed with minimal risk and wide acceptance. The aim of this study is to evaluate selected lncRNAs in plasma as potential diagnostic biomarkers in CRC. Methods Prospective cohort study between patients operated on for CRC (cases) and healthy patients (controls). Blood samples were processed in the biobank to obtain plasma by centrifugation. Subsequently, the levels of three CRC-related lncRNAs (HOTAIR, CCAT2 and PVT1) were determined in the laboratory of the Electroanalysis Group of the University of Oviedo (GEUO). Results In the initial results, an overexpression of the three genes (HOTAIR, CCAT2 and PVT1) was observed in CRC patients, with HOTAIR being the one that best differentiates between CRC and healthy patients. In addition, the combined determination of the three lncRNAs could obtain better results than the individual determination of each of them. Conclusions The lncRNAs studied are overexpressed in the CRC patient sample. The sample size needs to be increased to confirm this trend. It is logical to postulate that molecular technologies will lead to the development of better screening modalities and individualised treatments.

Diagnostic Value of Carcinoembryonic Antigen Combined with Multi-Inflammatory Cell Ratios in Colorectal Cancer.

Purpose To evaluate the diagnostic value of carcinoembryonic antigen (CEA) combined with inflammatory cell ratios in colorectal cancer (CRC). Methods This retrospective study compared the data of CRC patients with healthy controls. The CEA levels were measured, and the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection. Spearman's rank correlation test was used to analyze the correlation between CEA and NLR, d-NLR, and PLR. Results Inflammatory cell ratios and CEA were significantly higher in the CRC group. ROC curve analysis showed that NLR, d-NLR, and PLR had good diagnostic efficacy. The threshold showed that NLR, d-NLR, and PLR were all related to TNM stage, not to age, gender, tumor location, and degree of differentiation. CEA combined with NLR, d-NLR, and PLR (CNDNP) had a significant diagnostic value in CRC. Correlation studies showed that CEA was positively correlated with NLR and d-NLR but not with PLR. Conclusion The combination of CEA with CNDNP might be a valuable indicator for CRC diagnosis.

Upregulated Linc01836 in Serum Promisingly Serving as a Diagnostic and Prognostic Biomarker for Colorectal Cancer.

Objectives: Colorectal cancer (CRC) is a common carcinoma of the gastrointestinal tract with high incidence and mortality worldwide. Studies have shown that long noncoding RNAs (lncRNAs) play important roles in CRC. Our purpose is to investigate the potential of serum Linc01836 as a diagnostic and prognostic marker in CRC. Methods: We evaluated the expression of Linc01836 via quantitative real-time polymerase chain reaction (qRT-PCR). The serum CEA, CA19-9, Cyfra21-1, and CA72-4 concentrations were measured by Architect I4000 SR. Receiver operating characteristic (ROC) curves were plotted to estimate the diagnostic value in CRC. Relationship between serum Linc01836 expression and clinicopathological characteristics of CRC cases was analyzed via chi-square test. The underlying mechanism of Linc01836 on the development and prognosis in CRC was predicted by bioinformatic analysis. Results: The method of qRT-PCR for Linc01836 detection was confirmed with high precision and specificity. Serum Linc01836 expression in CRC patients was significantly higher than that in healthy donors (p < 0.0001) and benign patients (p < 0.0001), and declined after resection (p < 0.01). High expression of Linc01836 was associated with histological stage (p = 0.002) and lymph node metastasis (p = 0.006). In addition, serum Linc01836 could effectively differentiate CRC patients from the healthy folks, with favorable area under the curve (AUC) of 0.809 (95% CI: 0.757–0.861, p < 0.001). What is more, the combination of serum Linc01836, CEA, and Cyfra21-1 could improve diagnostic sensitivity (92.0%). Linc01836 was averagely located in the nucleus and cytoplasm, suggesting that it might participate in CRC progression and prognosis through the crosstalk among lncRNAs, miRNAs, and mRNAs. Conclusion: Linc01836 may serve as a valuable noninvasive biomarker for population screening, early detection, and clinical surveillance of CRC.

Investigating the Relationship Between the Expression Level of Mucin Gene Cluster (MUC2, MUC5A, and MUC5B) and Clinicopathological Characterization of Colorectal Cancer

Background: Colorectal cancer (CRC) is one of the most common cancers in the world and has a high mortality rate. It is accepted that dysfunction in the expression of mucins are associated with the occurrence and development of CRC. Therefore, the present study aimed to investigate the expression of MUC2, MUC5A, and MUC5B genes in CRC and their relationship with clinicopathological variables. Materials and Methods: The population included 28 patients after a colonoscopy and confirmation of the results. Tumors and parallel adjacent normal tissues from CRC patients were collected. RNA extraction and cDNA synthesis were performed using the corresponding kits. The gene primer was designed and RT-PCR was used to evaluate gene expression. The t-test and ANOVA were used to examine the differences between the different groups. Data analysis was performed using Prism8 software. Tumors from CRC patients were retrospectively collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Results: The results showed that the expression of MUC2, MUC5A, and MUC5B genes was lower in patients with CRC aged 50 years or younger than was in older patients (P&lt;0.05). Only the MUC5B gene expression was associated with tumor grades, which was higher in poorly differentiated tumors. The expression of MUC5A and MUC2 genes was higher in stage IV of the tumor than in other stages (P&lt;0.05). Conclusion: Among the changes in the expression of MUC secretory genes, including MUC2, MUC5A, and MUC5B and clinicopathological variables, there was a relationship that could have prognostic and diagnostic value in CRC. [GMJ.2021;10:e2030]

Investigating the Relationship Between the Expression Level of Mucin Gene Cluster (MUC2, MUC5A, and MUC5B) and Clinicopathological Characterization of Colorectal Cancer.

Background:Colorectal cancer (CRC) is one of the most common cancers in the world and has a high mortality rate. It is accepted that dysfunction in the expression of mucins are associated with the occurrence and development of CRC. Therefore, the present study aimed to investigate the expression of MUC2, MUC5A, and MUC5B genes in CRC and their relationship with clinicopathological variables.Materials and Methods:The population included 28 patients after a colonoscopy and confirmation of the results. Tumors and parallel adjacent normal tissues from CRC patients were collected. RNA extraction and cDNA synthesis were performed using the corresponding kits. The gene primer was designed and RT-PCR was used to evaluate gene expression. The t-test and ANOVA were used to examine the differences between the different groups. Data analysis was performed using Prism8 software. Tumors from CRC patients were retrospectively collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Results:The results showed that the expression of MUC2, MUC5A, and MUC5B genes was lower in patients with CRC aged 50 years or younger than was in older patients (P<0.05). Only the MUC5B gene expression was associated with tumor grades, which was higher in poorly differentiated tumors. The expression of MUC5A and MUC2 genes was higher in stage IV of the tumor than in other stages (P<0.05). Conclusion: Among the changes in the expression of MUC secretory genes, including MUC2, MUC5A, and MUC5B and clinicopathological variables, there was a relationship that could have prognostic and diagnostic value in CRC. Conclusion:None.

Can combination of CEA, CA 19-9, and CA242 improve diagnostic sensitivity and diagnostic value for colorectal cancer: A Meta-analysis

Can combination of CEA, CA 19-9, and CA242 improve diagnostic sensitivity and diagnostic value for colorectal cancer: A Meta-analysis

High Expression of Long Noncoding RNA 01410 Serves as a Potential Diagnostic and Prognostic Marker in Patients with Colorectal Cancer.

Long noncoding RNA (lncRNA)-mediated dysregulation is closely associated with various malignant tumors. However, the clinical significance of aberrant lncRNA expression in colorectal cancer (CRC) is still elusive. Differentially expressed LINC01410 in CRC was detected by analyzing the data from The Cancer Genome Atlas (TCGA). The expression level of LINC01410 was identified in 18 pairs of CRC tissues by real-time PCR assay at our center. Real-time PCR was also used to detect the expression of serum LINC01410 in serum obtained from 51 patients with primary CRC, 38 patients with colorectal polyps, and 50 healthy controls. Correlation and receiver operating characteristic curves (ROC) of CRC patients from the TCGA and our center were also carried out to assess the predictive value of LINC01410. The relative expression level of LINC01410 in CRC tissues and matched adjacent normal tissues was 2.268 (1.518, 3.359) and 0.962 (0.661, 1.719) (p < 0.05). Serum LINC01410 in CRC, colorectal polyps, and healthy control groups were 2.191 (1.505, 3.145), 1.665 (1.282, 2.237), and 1.000 (0.787, 1.227), respectively (p < 0.05). LINC01410 expression correlated with lymph node metastasis and TNM stages (p < 0.05). ROC curves revealed its significant diagnostic value in CRC, which was better than CEA and CA199. A new model combining LINC01410, CEA, and CA199 yielded a good diagnostic efficacy for CRC patients, showing the highest sensitivity and AUC. Our study demonstrated that LINC01410 was upregulated in CRC and the high expression of LINC01410 was associated with poor prognosis, suggesting its possible role as a potential marker for CRC.

LINC00565 promotes the progression of colorectal cancer by upregulating EZH2.

The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). The relative levels of LINC00565 and EZH2 in CRC tissues, based on their Tumor-Node-Metastasis stage and tumor size, were detected by reverse transcription-quantitative polymerase chain reaction. The diagnostic value of LINC00565 in CRC was assessed by depicting receiver operating characteristic curves. Pearson's correlation test was applied to analyze the expression correlation between LINC00565 and EZH2 in CRC tissues. The transfection efficacy of three LINC00565 small interfering RNAs was examined in CRC HCT116 and SW480 cell lines. After knockdown of LINC00565, the proliferative and migratory abilities of CRC cells were detected by Cell Counting Kit-8 and Transwell assays, respectively. The subcellular distribution of LINC00565 was analyzed, and the interaction between LINC00565 and EZH2 was determined by RNA immunoprecipitation. Finally, co-regulation of LINC00565 and EZH2 on CRC cell functions was explored by performing rescue experiments. Results showed that LINC00565 was upregulated in CRC tissues, especially in patients with stage III+IV and in those with large tumor sizes, suggesting its diagnostic value in CRC. EZH2 was also upregulated in CRC tissues, showing a positive correlation with LINC00565. LINC00565 was mainly expressed in the cytoplasm and was found to bind with EZH2. Validation was performed by overexpressing EZH2, which abolished the role of silenced LINC00565 in regulating proliferative and migratory abilities in CRC. Therefore, the upregulation of LINC00565 in CRC tissues was found to stimulate the aggravation of CRC by upregulating EZH2.

FANCF hypomethylation is associated with colorectal cancer in Han Chinese.

Fanconi anemia complement group F (FANCF) is known to be involved in DNA repair, and the overexpression of FANCF protein leads to cell proliferation and ultimately to cancer. The purpose of this study was to assess whether FANCF methylation was associated with colorectal cancer (CRC). A case-control experiment was conducted to study the association between FANCF methylation and CRC. We used quantitative methylation-specific PCR to measure the FANCF promoter methylation, and the percentage of methylation reference (PMR) to quantify the FANCF promoter methylation level. To investigate the effect of the selected FANCF fragment on gene expression regulation, we also performed a dual-luciferase reporter gene assay. The results indicated that FANCF methylation in CRC tumor tissues was significantly lower than that in the nontumor tissues (median PMR: 44.86% vs. 65.77%, p=0.00001). Analysis of receiver-operating characteristic curves showed that FANCF hypomethylation had a diagnostic value for CRC (area under curve [AUC]: 0.670, sensitivity: 55.8%, specificity: 71.7%, p=0.00001). The dual-luciferase reporter assay showed that the FANCF fragment upregulated gene expression (fold change: 1.93, p=0.002). Research demonstrates for the first time that FANCF hypomethylation is significantly associated with CRC risk. FANCF hypomethylation may ultimately increase the risk of CRC by upregulating the expression of FANCF.

A panel of six-circulating miRNA signature in serum and its potential diagnostic value in colorectal cancer

AimColorectal carcinoma (CRC) is one of the most prevalent cancers throughout the world. Circulating serum-derived microRNAs (miRNAs, miRs) can be used as non-invasive biomarkers for CRC diagnosis. This study aimed to identify a panel of six serum exosomal miRNAs as novel diagnostic biomarkers for CRC. Main methodsExosomes were isolated and characterized from the conditioned media of the human colon adenocarcinoma cells (HCT-116 and Caco2). Sera were isolated from peripheral blood of 45 CRC and also 45 healthy individuals. The expression levels and diagnostic value of candidate circulating miRNAs (miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a) were measured through quantitative real-time PCR. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic accuracy of selected miRNAs. The association of candidate miRNAs and clinicopathological characteristics e.g. tumor node metastasis (TNM) staging and lymph node metastasis (LNM) were further evaluated. Key findingsCirculating serum miR-19a, miR-20a, miR-150, and let-7a were significantly up-regulated in CRC patients, while miR-143 and miR-145 showed a significant down-regulation. The higher levels of miR-143 and miR-145 in patients with TNM stage I-II were detected, whereas miR-19a, miR-20a, miR-150, and let-7a were highly expressed in TNM stage III. The expression levels of miR-19a, miR-20a, and miR-150 were positively correlated with LNM status, while the expression levels of miR-143 and miR-145 were lower in patients with LNM. Area under the ROC curves of miR-19a, miR-20a, miR-150, miR-143, miR-145, and let-7a were 0.87, 0.83, 0.75, 0.76, 0.78 and 0.71, respectively. SignificanceWe established a panel of six-circulating miRNA signature (i.e. miR-19a, miR-20a, miR-143, miR-145, miR-150, and let-7a) in serum as a non-invasive biomarker for CRC diagnosis. These findings confirm that serum-derived miRNAs have a strong potential to be a diagnostic biomarker for patients with CRC.

Diagnostic value and prognostic significance of LI-cadherin and miR-378e in colorectal cancer.

Expression levels of LI-cadherin and miR-378e in the serum of patients with colorectal cancer, and the diagnostic value and prognostic significance in colorectal cancer were investigated. A total of 110 patients who were diagnosed with colorectal cancer in Weihai Central Hospital, from January 2012 to November 2014, were selected and enrolled in the experimental group, and 90 healthy subjects who underwent physical examination were enrolled in the control group. The expression level of miR-378e in serum was detected by reverse transcription-quantitative PCR and the expression of LI-cadherin in serum was detected by ELISA. ROC curves of LI-cadherin and miR-378e were drawn and the sensitivity and specificity of the diagnosis were estimated. The association of the expression levels of LI-cadherin and miR-378e with the survival of the patients was analyzed. LI-cadherin and miR-378e expression levels were significantly higher in the control group than those in the experimental group (P<0.001). LI-cadherin was significantly associated with the pathogenic site, the lymphatic metastasis, depth of infiltration, degree of differentiation and clinical stage (P<0.05). The sensitivity and specificity of the LI-cadherin combined with miR-378e detection were respectively 86 and 94%; the sensitivity of miR-378e detection was the highest, as well as the specificity of the combined detection. At the end of the follow-up period, the survival rates of the patients in the LI-cadherin high-expression group and miR-378e high-expression group were significantly higher than those in the low-expression groups (P<0.05). There was a significant positive correlation between the LI-cadherin and miR-378e expression levels in both the experimental and control group (r=0.5845 and 0.6356, respectively; P<0.05). In conclusion, LI-cadherin and miR-378e are expressed at low levels in colorectal cancer, suggesting that they have a good diagnostic value for colorectal cancer and can be used as biomarkers for colorectal cancer prognosis.

Plasma Lysyl-tRNA Synthetase 1 (KARS1) as a Novel Diagnostic and Monitoring Biomarker for Colorectal Cancer

Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.

Improved diagnostic value by combining plasma PON1 level with tumor biomarkers in Colorectal Cancer patients.

The incidence of colorectal cancer (CRC) ranks third among all cancers in China and improvements in screening for CRC have an important impact on prevention and control of the disease. Paraoxonase 1 (PON1) is a calcium ion-dependent hydrolase that is widely distributed in tissue. Its diagnostic value in colorectal cancer has been reported, but the diagnostic value of combining PON1 with carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 12-5 (CA12-5) in colorectal cancer has not been evaluated. Experiments were carried out in a total of 284 CRC patients and 90 healthy controls. The primary cohort was randomly divided into training and validation sets. The levels of PON1 in plasma of CRC patients were significantly lower than that in the healthy controls (P < 0.001). It showed excellent diagnostic value with the AUC reaching 0.750 for the training set and 0.742 for the validation set. Furthermore, combining PON1 with CEA, CA12-5, CA19-9 could better classify CRC patients (AUC rising from 0.821, 0.716, 0.712 to 0.875, 0.817 and 0.814, respectively, in the training set, from 0.818, 0.581, 0.593 to 0.854, 0.770, and 0.772 in the validation set). In conclusion, PON1 can serve as a diagnostic biomarker for CRC and raise the sensitivity and specificity when incorporated with traditional tumor biomarkers.

A 3-circular RNA signature as a noninvasive biomarker for diagnosis of colorectal cancer

BackgroundCircular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed.MethodsCircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs.ResultsTotally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis.ConclusionIn conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

Potential Diagnostic Value Of Combining Inflammatory Cell Ratios With Carcinoembryonic Antigen For Colorectal Cancer.

PurposeTo evaluate the diagnostic value of combining the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) or lymphocyte–monocyte ratio (LMR) with carcinoembryonic antigen (CEA) in patients with colorectal cancer (CRC).Patients and methodsThe diagnostic performance of inflammatory makers and CEA was evaluated in cohort 1 (664 patients with CRC, 336 patients with colorectal polyps and 664 healthy controls) and validated in cohort 2 (87 patients with CRC and 87 healthy controls) by using receiver operating characteristic curve analysis.ResultsIn cohort 1, the NLR, PLR and CEA levels were significantly higher, while the LMR was markedly lower in patients with CRC than in healthy controls. The PLR and LMR were significantly associated with invasion depth and lymph node metastasis. Moreover, significant differences in the PLR and LMR were observed between patients with stage I/II CRC and healthy or polyp controls and those with stage III/IV CRC. Using the NLR, PLR or LMR with CEA resulted in a significantly larger area under the curve (AUC) than any of them used alone. Combining the PLR and LMR with CEA exhibited the best diagnostic value for CRC (AUC=0.892). The AUCs of this combination were 0.864 and 0.783 for distinguishing stage I/II CRC from healthy and polyp controls, respectively. When we used the same cut-off values to assess the diagnostic ability of these markers in cohort 2, similar results were observed, and the PLR, LMR and CEA combination also showed the highest accuracy (AUC=0.936).ConclusionCombining inflammatory cell ratios with CEA could improve the diagnostic efficacy for CRC patients. The combination of the PLR and LMR with CEA might be a valuable indicator in the early detection and monitoring of CRC patients.