non-CRC Controls Research Articles

Plasma metabolomic differences in early-onset compared to average-onset colorectal cancer

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I–IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3–0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies.

TCF21 rs2327429 and TCF21 rs12190287 are associated with colorectal cancer in a Chinese population.

Aims: TCF21 is considereda tumor suppressor gene. This work was designed to explore the associations between TCF21 polymorphisms and colorectal cancer (CRC) susceptibility. Methods: A case-control study was designed with 421patients with CRCand 469 non-CRC controls. Six tagging single-nucleotide polymorphisms (rs2327429 T>C, rs2327430 T>C, rs2327433 A>G, rs12190287 C>G, rs7766238 G>A andrs4896011 T>A) were genotyped byligase detection reaction of PCR. Results: TCF21 rs2327429 and rs12190287 polymorphisms were associated with CRC susceptibility in aChinese Han population. Conclusion: rs2327429 and rs12190287 polymorphisms may be predictive ofCRC susceptibility in Chinese Han populations.

Parvimonas micra infection enhances proliferation, wound healing, and inflammation of a colorectal cancer cell line.

The gut microbiota Parvimonas micra has been found to be enriched in gut mucosal tissues and fecal samples of colorectal cancer (CRC) patients compared with non-CRC controls. In the present study, we investigated the tumorigenic potential of P. micra and its regulatory pathways in CRC using HT-29, a low-grade CRC intestinal epithelial cell. For every P. micra-HT-29 interaction assay, HT-29 was co-cultured anaerobically with P. micra at an MOI of 100:1 (bacteria: cells) for 2 h. We found that P. micra increased HT-29 cell proliferation by 38.45% (P=0.008), with the highest wound healing rate at 24 h post-infection (P=0.02). In addition, inflammatory marker expression (IL-5, IL-8, CCL20, and CSF2) was also significantly induced. Shotgun proteomics profiling analysis revealed that P. micra affects the protein expression of HT-29 (157 up-regulated and 214 down-regulated proteins). Up-regulation of PSMB4 protein and its neighbouring subunits revealed association of the ubiquitin-proteasome pathway (UPP) in CRC carcinogenesis; whereas down-regulation of CUL1, YWHAH, and MCM3 signified cell cycle dysregulation. Moreover, 22 clinically relevant epithelial-mesenchymal transition (EMT)-markers were expressed in HT-29 infected with P. micra. Overall, the present study elucidated exacerbated oncogenic properties of P. micra in HT-29 via aberrant cell proliferation, enhanced wound healing, inflammation, up-regulation of UPPs, and activation of EMT pathways.

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.

Combined Efficacy of CXCL5, STC2, and CHI3L1 in the Diagnosis of Colorectal Cancer.

Objective To improve the diagnostic capacity of serum biomarkers for colorectal cancer (CRC), we introduced three novel indicators, namely, the C-X-C motif chemokine ligand 5 (CXCL5), stanniocalcin 2 (STC2), and chitinase 3 like 1 (CHI3L1) and assessed their performances in the detection of CRC. Methods A total of 887 serum samples (153 health, 342 polyps, and 392 CRCs) were collected. Concentrations of CXCL5, STC2, and CHI3L1 were measured by the ELISA. CEA and CA199 were determined by electrochemiluminescence. Binary logistic regression was used to build the combination model. ROC analysis was used to evaluate the performance of biomarkers alone or in combination. Results Model_2 that based on CXCL5, STC2, and CHI3L1 was the best approach in discriminating CRC from non-CRC controls (AUC, 0.943 (0.922–0.960); sensitivity, 0.848; specificity, 0.917; and accuracy, 0.887 in the training cohort and 0.959 (95% CI 0.927–0.980), 0.878, 0.917, and 0.900 in the testing cohort, respectively). In the detection of early CRC, Model_2 revealed AUC, sensitivity, specificity, and accuracy of 0.925 (0.897–0.947), 0.793, 0.917, and 0.886 in the training cohort and those of 0.926 (0.979–0.959), 0.786, 0.931, and 0.898 in the testing cohort. Furthermore, Model_2 exhibited an excellent diagnostic performance in CEA-negative cases (0.938 (0.913–0.957), 0.826, 0.917, and 0.888 in the training cohort and 0.961 (0.925–0.983), 0.887, 0.931, and 0.918 in the testing cohort). As used alone, STC2 achieved the capacities that is second only to that of Model_2 (0.866 (0.837–0.892), 0.859, 0.842, and 0.853 in the training cohort and 0.887 (0.842–0.923), 0.922, 0.799, and 0.853 in the testing cohort). STC2 alone also yielded acceptable results for early CRC detection (0.815 (0.776–0.849), 0.767, 0.849, and 0.829 in the training cohort and 0.870 (0.812–0.914), 0.952, 0.799, and 0.833 in the testing cohort). Moreover, STC2 maintained diagnostic accuracy for CRC patients with negative CEA (0.874 (0.842–0.901), 0.862, 0.849, and 0.853 in the training cohort and 0.898 (0.848–0.936), 0.930, 0.801, and 0.842 in the testing cohort). In comparison, the performances of the CEA and CA199 based Model_1 were far from satisfactory, especially in early cases (0.767 (0.726–0.805), 0.491, 0.863, and 0.771 in the training cohort and 0.817 (0.754–0.870), 0.476, 0.889, and 0.796 in the testing cohort). Conclusions STC2 was a promising serum biomarker for CRC diagnosis either used alone or in combination with CXCL5 and CHI3L1.

Colorectal microbiota after removal of colorectal cancer.

The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BackgroundColorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance.MethodsThe target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1.ResultsTotal 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1.ConclusionCLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries

BackgroundThe incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a ‘resource-light’ sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries.MethodsWe assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries.ResultsThe microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia).ConclusionsThis study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.

Parvimonas micra, Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients.

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n=208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p =0.001) or liver metastasis (p =0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p =0.024) and multivariate (p =0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n=590 vs 47; p <0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.

Rectal swab gene expression as a non-invasive biomarker for CRC screening

Abstract BACKGROUND Aberrant gene levels in rectal swab specimens are potential non-invasive biomarkers for the early detection of colorectal cancer. The aim of this study was to investigate the expression level of dysregulated genes in CRC in rectal swab specimens from normal subjects and CRC patients, and evaluate the potential of this approach as a non-invasive biomarker for CRC diagnosis. METHODS We performed RNA extraction and reverse transcription of the rectal swab specimens, then applied quantitative polymerase chain reaction to determine the expression level of 15 genes which have been previously reported to show dysregulation during CRC development. RESULTS Our results showed that CD44, IL8, CXCR2 and c-myc were significantly overexpressed in rectal swab specimens of CRC patients when compared to control subjects in both the training and validation studies, suggesting that gene levels of these four genes were potential biomarker to discriminate CRC from non-CRC subjects. Further evaluation showed that a panel of these 4 genes was able to identify CRC patients with an area under the curve of 0.74 for the training study and 0.79 for the validation study. Finally, we tested the predictive value of the 4-gene signature in a prediction study of 55 subjects (including 25 CRC patients and 30 non-CRC control subjects). The 4-gene signature correctly identified 16 of 20 CRC patients (80% sensitivity) and 29 of 35 non-CRC subjects (82.9% specificity). CONCLUSION Our data demonstrated the promising potential of the gene signature in rectal swab specimens as a noninvasive biomarker for CRC diagnosis.

β6 -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

ATP-binding cassette member B5 (ABCB5) promotes tumor cell invasiveness in human colorectal cancer

ABC member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression. In human-to-mouse CRC tumor xenotransplantation models that exhibited circulating tumor mRNA, we observed that cancer-specific ABCB5 knockdown significantly reduced detection of these transcripts, suggesting that the knockdown inhibited tumor invasiveness. Mechanistically, this effect was associated with inhibition of expression and downstream signaling of AXL receptor tyrosine kinase (AXL), a proinvasive molecule herein shown to be produced by ABCB5-positive CRC cells. Importantly, rescue of AXL expression in ABCB5-knockdown CRC tumor cells restored tumor-specific transcript detection in the peripheral blood of xenograft recipients, indicating that ABCB5 regulates CRC invasiveness, at least in part, by enhancing AXL signaling. Our results implicate ABCB5 as a critical determinant of CRC invasiveness and suggest that ABCB5 blockade might represent a strategy in CRC therapy, even independently of ABCB5's function as an MDR mediator.

Insights into insulin resistance, lifestyle, and anthropometric measures of patients with prior colorectal cancer compared to controls: A National Health and Nutrition Examination Survey (NHANES) Study

BackgroundInsulin resistance (IR) increases the risk of index colorectal cancer (CRC) development. Limited data exist on IR values, lifestyle, and anthropometric alterations of patients after CRC diagnosis, a population at high risk for CRC recurrence. MethodsThis is a retrospective cohort study using the National Health and Nutrition Examination Survey (NHANES), 1999-2010. We identified patients with and without prior CRC above age 50. Our outcomes were lifestyle, anthropometric measures, and IR measured using the triglyceride to high-density lipoprotein ratio and the homeostasis model assessment IR. ResultsThere were 146,841 patients with prior CRC and 26,979,507 without prior cancer (controls) in our cohort. Prior patients with CRC were significantly older than controls (75.8 vs 62.3, P < 0.01), however, there were no significant differences in gender, ethnicity, income, caloric intake, tobacco use or alcohol consumption between both groups. Multivariate analysis revealed no difference between prior patients with CRC and controls in triglyceride to high-density lipoprotein ratio (adjusted percentage change = −2.17; 95% CI: −27.96 to 18.43) or homeostasis model assessment IR (adjusted percentage change = −6.85; 95% CI: −35.74 to 15.90). Despite similar weight at age 25, prior CRC subjects had lower weights compared to controls (at time of NHANES survey, one and 10 years before survey and greatest weight). Furthermore prior CRC subjects gained less weight in the 10 years before survey. ConclusionPatients with prior CRC above age 50 have no conclusive evidence of increased IR compared to non-CRC controls. This is possibly due to lesser weight gain in the peri-CRC diagnosis or treatment period. Future efforts should focus on alternate etiologies for the increased CRC recurrence in this high-risk group.

Prevalence of pks-positive Escherichia coli in Japanese patients with or without colorectal cancer

BackgroundRecent studies show that some Escherichia coli strains possessing a gene cluster named the pks island might have a causative role in the development of human colorectal cancer (CRC). In several reports from Europe, they are found more prevalently in colon tissue specimens derived from CRC patients compared to those from controls. In this study we sought to clarify the difference in pks prevalence between CRC patients and non-CRC controls in the Japanese population, by using non-invasive sample collection technique during colonoscopy.MethodsColonic lavage samples were collected during diagnostic colonoscopy, and bacterial DNA within each sample was extracted. Fecal DNA samples were then examined for pks island genes using conventional qualitative PCR and real-time quantitative PCR. In some patients biopsy samples were also collected in the same session of colonoscopy, and the correlation between the pks status of the colonic lavage sample and the biopsy sample of the same patients was evaluated.ResultsTwelve out of thirteen patients (92%) showed the same pks status by colonic lavage sample and biopsy sample, suggesting the usefulness of colonic lavage samples as a surrogate for biopsy samples. A total of 98 colonic lavage samples were collected, which included 35 from CRC patients, 37 from adenoma patients, and 26 from controls. The pks-positive bacterial DNA was detected in 43, 51, and 46% of colonic lavage samples from CRC, adenoma, and control patients, respectively, and there was no significant difference among diseases. Real-time quantitative PCR showed no significant difference in the relative concentrations of pks-positive bacterial DNA among diseases. Age, gender, location of CRC, CRC staging, or k-ras gene status was not associated with pks prevalence.ConclusionsAlthough the method of collecting fecal DNA from colonic lavage samples was safe and technically feasible, factors other than pks-positive bacteria appear to play more important roles in CRC development in this cohort.

Peripheral blood mRNA signature for colorectal cancer screening.

e14030 Background: Colorectal cancer is the second and third leading cause of cancer-related mortality for women and for men in the world. It is believed that more than 50% of these deaths may have been prevented through the use of screening tests. The compliance with current CRC screening recommendations remains poor. A simple blood-based test would represent an interesting alternative. We used DNA-microarrays and PAXgene to study the gene expression repertoires in peripheral blood, suitable for new biomarker discovery. Methods: 119 CRC patients and 101 non-CRC controls were enrolled in our study. RNA extracted from peripheral blood samples collected in PAXgene tubes, were analysed after NuGEN WT-Ovation RNA amplification, using Affymetrix GeneChip HG-U133 Plus 2.0 Array. Molecular signature discovery was performed based on 5-fold cross validation method, which means 4/5 of samples were used as internal train fold, prediction model was created with the top 100 genes scored by RFE-SVM, and then model performance was assessed with rest of samples. The process was run for 1000 iterations. Eventually, accuracy, sensitivity and specificity were used to measure the overall performance. Furthermore, we estimated the signature performance in an independent validation set, with 45 CRC patients and 47 non-CRC controls. Results: The overall performance based on cross validation process reached 95% (94.9, 95.3) accuracy, 95% (94.8, 95.2) sensitivity and 95% (95.0, 95.4) specificity. The signature performance in the independent test set reached 87.7% (77.9, 92.7) accuracy, 73.3% (57.8, 84.9) sensitivity and 100% (90.6, 100.0) specificity. The majorities of signature genes represent MHC class II receptoe activity, scavenger receptor activity, T cell proliferation and signal transduction information, implying the molecular changes occurring during disease progression. Conclusions: Our results demonstrated the feasibility of using gene expression profiling in peripheral blood to identify novel biomarkers. The CRC biomarker panel learned on the present dataset was considered as a promising transcriptomic biomarker for colorectal cancer screening.

Association of C-reactive Protein Gene Polymorphisms and Colorectal Cancer

An elevated plasma level of C-reactive protein (CRP) is a risk for, and prognostic factor of, colorectal cancer (CRC). In other reports of CRP concerning cardiovascular disease, CRP level correlated with its gene polymorphisms. We hypothesized that CRP polymorphisms associate risk and prognosis of CRC. This study enrolled 421 patients with CRC and 218 healthy control subjects. After preliminary studies, we selected four single nucleotide polymorphisms (SNPs) in the CRP gene: +2147A > G (rs1205), +942G > C (rs1800947), -717A > G (rs2794521), and -757T > C (rs3093059). At first, analyzing distributions of four SNPs between CRC case and non-CRC control groups was performed. Subsequently, the impacts of these SNPs with other prognostic factors of disease-free interval (DFI) and cancer-specific survival (CSS) were analyzed using uni- and multivariate Cox regression analyses. The case and control groups differed in the frequency of -757T > C (P = 0.002). The CRC case group had a higher percentage of the TT genotype (odds, 1.75). Regarding prognoses, multivariate analyses revealed that four factors, including stage (I, II, III), gross tumor type (polypoid, ulcerative, infiltrative), location (right, left, rectum), and -757T > C SNP (odds, 1.29; P = 0.048), correlated with DFI; two factors, including stage and +2147A > G SNP (odds, 0.71; P = 0.03), correlated with CSS. The -757T > C SNP is a risk for and prognostic factor of DFI; the +2147A > G SNP is a prognostic factor of CSS. CRP polymorphisms associate the risk and survival of CRC.