Early Diagnosis Of Colon Cancer Research Articles

Expression and diagnostic value of miR-34c and miR-141 in serum of patients with colon cancer.

Expression of miR-34c and miR-141 in serum of colon cancer patients and their association with clinicopathological features and diagnostic value for colon cancer were investigated. A total of 64 patients with colon cancer admitted to Hubei Cancer Hospital from January 2016 to March 2018 were included in the experimental group, and 64 healthy subjects undergoing physical examination during the same period were the control group. The expression of miR-34c and miR-141 in serum of patients in the two groups were detected by RT-qPCR, and the association of miR-34c and miR-141 with the clinicopathological characteristics of colon cancer patients was analyzed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of miR-34c and miR-141 in colon cancer. The expression of miR-141 in serum of patients in the experimental group was significantly higher than that in the control group (P<0.05). Expression of miR-34c in serum of patients in the experimental group was significantly lower than that in the control group (P<0.05) and the expression of miR-34c and miR-141 in serum of the experimental group were associated with tumor diameter, clinical stage, degree of differentiation and lymph node metastasis (P<0.05). AUC of serum miR-34c in the diagnosis of colon cancer was 0.857 (95% CI: 0.795-0.919), with the cut-off value of 0.800, the diagnostic sensitivity of 84.38%, and the specificity of 68.75% and AUC of serum miR-141 in the diagnosis of colon cancer was 0.876 (95% CI: 0.810-0.941), with the cut-off value of 0.282, the diagnostic sensitivity of 70.31%, and the specificity of 96.88%. The ROC curve for the diagnosis of colon cancer was further plotted in combination with serum miR-34c and miR-141. AUC of the two combined for the diagnosis of colon cancer was 0.929 (95% CI: 0.884-0.974), with the cut-off value of 0.566, the diagnostic sensitivity of 84.38%, and the specificity of 93.75%. In conclusion, miR-34c and miR-141 might be involved in the occurrence and progression of colon cancer and could be used as biological indicators for early diagnosis of colon cancer.

Development of a panel of serum IgG and IgA autoantibodies for early diagnosis of colon cancer.

Purpose: Our pilot study in a small cohort by ELISA showed that the levels and positive rates of serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ in early colon cancer (CC) group were significantly higher than that of colon benign lesion (CBL) group / healthy control (HC) group (P <0.01), which suggested that four autoantibodies might be valuable for the diagnosis of patients with CC at early stage. On the basis of pilot study, we intend to comprehensively elucidate the performance of four autoantibodies for the early diagnosis of CC in a large sample cohort, and explore the optimal panel of autoantibodies in the diagnosis of patients with CC at early stage.Methods: Western blot was used to define the ELISA results of serum anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA. The performances of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA were evaluated by ELISA for the early diagnosis of CC with 601 serum samples of 157 patients with CC at early stage, 144 patients with CC at advanced stage, 130 patients with CBL, and 170 HC, and then the performances of different combinations of four autoantibodies were analyzed for the development of an optimal panel for the early diagnosis of CC.Results: The results of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in western blotting were consistent with that in ELISA. The levels and positive rates of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in early CC group were significantly higher than that in CBL group/HC group (P <0.01), while had no significant difference from that in advanced CC group (P >0.05), of which anti-TIF1γ-IgA showed the highest area under the receiver operating characteristic curve (AUC) of 0.716 for the patients with CC at early stage, with 25.5% sensitivity and specificity at 96.7%. Additionally, a panel of anti-p53, HRAS-IgG and anti-TIF1γ-IgA showed the highest AUC among all possible combinations of four autoantibodies, up to 0.737, with 47.1% sensitivity at 92.0% specificity.Conclusions: Serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ show the diagnostic value for the patients with CC at early stage, of which anti-TIF1γ-IgA is demonstrated to be a preferable biomarker, and an optimal panel comprised of anti-p53, HRAS-IgG and anti-TIF1γ-IgA might contribute to the further improvement of early diagnosis for CC.

106P - The risk of malignization incidence in patients with polyps and polyposis of the colon and rectum

BackgroundPolyps are considered as obligate precancerous disease. Different authors consider that percent of malignization ranges from 20% in single polyps to 95% in diffuse polyposis. Current research examines the results of the early diagnosis of colon cancer by using the biomarker CDKN2A for development of molecular-biological methods of prognostication. MethodsInvestigations were carried out in 30 patients during the period 2017-2019, the study included patients with single polyps, multiple polyps, polyposis of the colon, as well as patients without a history of neither familial nor sporadic cancer. 21 patients had polyposis, in 9 single colon polyps. The men were 19 women 11. The average age of patients was 52,4 ± 3,8 years. The levels of methylation of the gene CDKN2A were determined 18 patients. The material for the isolation of DNA was a serum obtained from venous blood and and biopsy material in amount of 50 mg. DNA extraction was held according to standards. After the conversion of DNA methyl-specific PCR was held. ResultsAmong 30 patients with polyps and polyposis of the colon serum gene CDKN2A methylated DNA was detected in 18 patients. In 4 patients malignization of the polyp was determined. The volume of surgical intervention in patients with malignization was the same as cancer. It patients without malignization surgical intervention was limited with resection of the intestine without lymph dessection. In 8 patients the test result was negative. We did not perform surgical intervention to these patients they were sent to dynamic observation. Thus, the diagnostic efficacy in detection colorectal cancer in early diagnosis of by means of methylated DNA of the gene CDKN2A was - 60.1%. ConclusionsIf there is a positive test for methylation of the CDKN2A-gene, the risk of colorectal cancer is considered very high and these patients underwent surgical treatment. Application of molecular biological marker CDKN2A may be an effective method in early diagnosis of malignization of polyps. This method of diagnosis requires a more in-depth study, based on a study of a larger number of observations. Further investigations of the CDKN2a gene in ulcerative colitis, Krohn's disease, Lynch syndrome, Jeghers syndrome might be continued. Legal entity responsible for the studyNCC of Uzbekistan. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Chromogranin-A Expression as a Novel Biomarker for Early Diagnosis of Colon Cancer Patients.

Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein–protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

THE CASE FILES

THE CASE FILES

Targeting Upconversion Nanoprobes for Magnetic Resonance Imaging of Early Colon Cancer

Colon cancer (CC) is one of the most common intestinal malignancies and is difficult to detect in its early stage by magnetic resonance imaging (MRI) with currently used contrast agents (CAs). The development of targeted CAs contributes to the early diagnosis of CC and thereby enables early intervention and timely therapy. Considering the outstanding performance of upconversion nanoprobes (UCNPs) in high-performance MR and fluorescence imaging, a new type of nanoprobes with considerably enhanced imaging performance is developed herein. Carcinoembryonic antigen (CEA) antibody is conjugated onto the surface of UCNPs to achieve the targeted imaging of early CC tumors, which overexpress CEA. Both toxicity tests and histological/hematological examinations demonstrate the excellent biocompatibility of these CC-targeting nanoprobes, which possess great potential for clinical application in the early diagnosis of CC.

Isolation and Identification of miRNAs in exosomes derived from serum of colon cancer patients.

Objective: To isolate exosomes from the serum of colon cancer patients and identify RNAs in the small vesicles.Methods: ExoQuick-TC™ Exosome Precipitation Solution was used for exosome isolation and the shapes of exosomes were observed under a transmission electron microscope. Mass spectrometry was used to identify the classification of miRNAs encapsulated in exosomes, and the expression levels of miRNA-21,-133a, and -181b in exosomes were detected by RT-PCR.Results: Exosomes isolated from serum of colon cancer patients were circular-or oval-shaped and vary in size with a diameter of 40-100 nm. Mass spectrometry shows that the main RNAs in exosomes are small RNAs; the levels of these small RNAs in exosomes are significantly higher compared with fresh serum. There is still a tiny amount of small RNAs in exosome-free serum, but the amounts are significantly lower than that in exosomes. No more RNAs were detected in the repeated freezing and thawing serum, but there were still some RNAs detectable in the exosomes extracted from these serums. MiRNA-21, -133a and -181b can be detected in exosomes, and the level of miRNA-21 is associated with early diagnosis of colon cancer.Conclusion: This study proves that commercial kits for exosome separation are more convenient and time-saving and that mass spectrometry is capable of identifying the miRNAs in exosomes. Compared with direct extraction of miRNAs from the serum, the method of isolating exosomes from the serum firstly and then extracting miRNAs from the exosomes can enhance the stability and integrity of their inner miRNAs. Also, we demonstrate that the exosomal miRNA-21 expression is associated with the early diagnosis of colon cancer.

Mucins and associated glycan signatures in colon adenoma–carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer

Development of biomarkers that detect early stage resectable premalignant lesions of colon can provide critical aid in the prevention of colorectal cancer. Recent lines of evidence suggest the utility of mucin expression to predict malignant transformation of colon pre-neoplastic lesions. In this study, we investigated the combined expression of multiple mucins and mucin-associated glycans during the adenoma–carcinoma sequence of colon cancer progression. Further, we evaluated their applicability as markers for differentiating adenomas/adenocarcinomas from hyperplastic polyps. Immunohistochemical analyses performed on colon disease tissue microarrays revealed downregulation of MUC2 and MUC4 expression (p < 0.0001) while MUC1 and MUC5AC expressions were upregulated (p = 0.01) during adenoma–adenocarcinoma progression. Expression of MUC17 was downregulated in inflamed tissues compared to normal tissues, but its increased expression differentiated adenomas (p = 0.0028) and adenocarcinomas (p = 0.025) from inflammation. Glycan epitope-Tn/STn on MUC1 showed higher expression in hyperplastic polyps (p = 0.023), adenomas (p = 0.042) and adenocarcinomas (p = 0.0096) compared to normal tissues. Multivariate regression analyses indicated that a combination of MUC2, MUC5AC, and MUC17 could effectively discriminate adenoma–adenocarcinoma from hyperplastic polyps. Altogether, a combined analysis of altered mucins and mucin-associated glycans is a useful approach to distinguish premalignant/malignant lesions of colon from benign polyps.

Patients with Acromegaly Presenting with Colon Cancer: A Case Series.

Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). Colon cancer was identified in 2 patients (4.5%). Case 1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case 2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

Interference of Skp2 effectively inhibits the development and metastasis of colon carcinoma.

Colon cancer is a common type of malignancy in the digestive system. The aim of the present study was to investigate the role of S-phase kinase-associated protein2(Skp2) in colon carcinoma and to identify whether depletion of Skp2 by Skp2‑RNA interference (RNAi) attenuates the proliferation and migration of colon carcinoma. Three pairs of small interfering (si)RNA were designed based on the Skp2 gene sequence and the most effective one was used to silence the Skp2 gene in SW620 cells. Subsequent to the interference, quantitative polymerase chain reaction and western blot analysis were used for detecting the expression of Skp-2 mRNA and protein, respectively. The data demonstrated that the Skp2‑siRNA effectively inhibited proliferation (P<0.01), increased the levels of apoptosis and induced G0/G1phase arrest of the SW620 cells (P<0.01). Transfection of the Skp2 siRNA into SW620 cells effectively reduced Skp2 protein levels, while p27 protein levels increased. In the invivo experiments, a lentiviral vector of the Skp2-RNAi transfected into SW620 cells markedly inhibited Skp2 expression, as detected by immunohistochemical analysis of nude mice. Additionally, tumorigenicity experiments showed that inhibition of Skp2 significantly increased the survival rate of nude mice. Thus, the invitro and invivo results demonstrated that interference of Skp2 expression significantly inhibited the proliferation and induced the apoptosis of SW620cells. This suggests that Skp2 protein has an important role in the progression of colon cancer. Therefore, Skp2 may enable the early diagnosis of colon cancer and provide new insights into molecular targets for cancer therapy.

基于拉曼光谱和多元统计分析技术的结肠癌早期诊断

基于拉曼光谱和多元统计分析技术的结肠癌早期诊断

Colonoscopia con insuflación de dióxido de carbono: ¿lujo o necesidad?

Colonoscopy is an essential diagnostic and therapeutic tool for many gastrointestinal diseases and is also a key element in the prevention and early diagnosis of colon cancer. Despite numerous technical advances, colonoscopy continues to be uncomfortable for patients, both during and after the procedure. To a large extent, the discomfort of colonoscopy depends on the need to distend the colon, which usually produces abdominal pain. Although ambient air is usually employed to expand and inflate the colon, in the last few years devices that allow carbon dioxide (CO2) insufflation in colonoscopy have been developed. This gas is a highly attractive option for pain-free colonoscopy.

Identification of candidate colon cancer biomarkers by applying a random forest approach on microarray data

Colon cancer is the third most common cancer and one of the leading causes of cancer-related death in the world. Therefore, identification of biomarkers with potential in recognizing the biological characteristics is a key problem for early diagnosis of colon cancer patients. In this study, we used a random forest approach to discover biomarkers based on a set of oligonucleotide microarray data of colon cancer. Real-time PCR was used to validate the related expression levels of biomarkers selected by our approach. Furthermore, ROC curves were used to analyze the sensitivity and specificity of each biomarker in both training and test sample sets. Finally, we analyzed the clinical significance of each biomarker based on their differential expression. A single classifier consisting of 4 genes (IL8, WDR77, MYL9 and VIP) was selected by random forests with an average sensitivity and specificity of 83.75 and 76.15%. The differential expression levels of each biomarker was validated by real-time PCR in 48 test colon cancer samples compared to the matched normal tissues. Patients with high expression of IL8 and WDR77, and low expression of MYL9 and VIP had a significantly reduced median survival rate compared to colon cancer patients. The results indicate that our approach can be employed for biomarker identification based on microarray data. These 4 genes identified by our approach have the potential to act as clinical biomarkers for the early diagnosis of colon cancer.

Analysis of the depolarizing properties of normal and adenomatous polyps in colon mucosa for the early diagnosis of precancerous lesions

Optical characterization of biological tissues by means of polarimetric techniques is an area of growing interest. Polarized light can be used for malignant neoplasms detection. To our knowledge, few studies have so far focused on lesions that are prone to result in cancer. In this work we present a polarimetric study of depolarization in prepathological tissues. Specifically, we will focus on premalignant lesions in human colon due to their clinical relevance. Colonic adenoma, the potential precursor of malignant adenocarcinoma, provokes significant structural modifications in colon mucosa that affect light depolarization. The depolarizing properties of normal and adenomatous polyps mucosa are compared. The average linear degree of polarization is shown to present a strong dependence with the precancerous state of the colonic tissue. This method has the potential to enable an early diagnosis of colon cancer.

The Potential Use of N-Myristoyltransferase as a Biomarker in the Early Diagnosis of Colon Cancer

Colon cancer is one of the most common malignant diseases and a major cause of mortality in the Western world. Metastasis to lymph nodes and other gastrointestinal organs, especially to the liver and lungs, is most common and occurs in up to 25% of cancer patients when initially diagnosed. The majority of colon cancers develop from noncancerous adenomatous polyps on the lining of the colon which grow over the years to become cancerous. If detected early, the surgical resections of the growth, often in combination with chemotherapy, significantly increases life expectancy. We have shown that the enzyme N-myristoyltransferase (NMT) which carries out lipid modification of several proteins (including many of those involved in oncogenesis) is expressed at higher levels in cancerous tissues from the colon. We have also shown that in peripheral blood mononuclear cells (PBMC) and bone marrow (BM) cells collected from colon cancer patients and from azoxymethane-induced rats the expression and localization of NMT is altered. We have observed strong positivity for NMT in immunohistochemical analysis for PBMC from colon cancer patients as compared to control groups. Furthermore, in the bone marrow (BM) mononuclear cells, NMT was found to be confined to the nuclei whereas in control groups it was observed to be located in the cytoplasm. In conclusion, this strikingly differential localization offers the basis of a potential investigational tool for screening or diagnosis of individuals at risk for or suspected of having colon cancer.

Milzverletzung nach Koloskopie

The increasing number of preventive screening investigations in the course of obtaining early diagnosis of colon cancer, has been leading to an increase in the number of colonoscopies in Germany. Splenic injury is one of the complications to be aware of, if postinterventional abdominal symptoms occur. This retrospective study was based on the answers to questionnaires sent to 220 members of the Working Party of Leading Hospital-Based Gastroenterologists. The response rate was 40%. Thirteen of the gastroenterologists reported a total of 16 splenic injuries, a rate of about one injury per 87,000 (about 0.001 %) this compares to a worldwide published splenic injury rate of 0.004 %. But the actual numbers are probably higher in Germany as well. In order to obtain a more exact complication rate in the future, splenic injuries should be reported centrally. This is possible by sending a report of the complication by e-mail to splenicinjury_colonoscopy@web.de.

Preliminary assessment of results obtained by the Endoscope Department of Great Poland Cancer Centre, Poznań, in the framework of the Screening Programme for Early Diagnostics of Colon Cancer in years 2004-2005

Summary Background Colonoscopy screening and polypectomy are one of the most effective ways to reduce the incidence of colon cancer. One of the best achievements in Poland is the Colorectal Screening Programme that was started in 2000. Aim The aim of our study is to present the results of the examination made by the Endoscope Department of Great Poland Cancer Centre in the framework of the Polish Screening Programme for early diagnosis of colon cancer in the years 2004 and 2005. Materials/Methods We admitted to the screening programme asymptomatic persons aged 50–65 years (main group), persons between 40 and 65 years old with familial history of colorectal cancer, and people aged 25–65 from HNPCC or FAP families. Results We examined 1000 individuals. 982 total colonoscopies (98.2% effectiveness) were done, and finally 806 polyps were removed. Adenomas were found in 83 removed polyps (10%), including neoplastics lesions in 24 (28.9%) cases: tubulovillous adenomas in 15 (18.1%), villous adenomas in 5 (6.0%) and serrated adenomas in 4 (4.8%) cases. Two of the removed polyps (0.2%) were malignant. Summarized colorectal neoplasia was detected in 26 (2.6%) participants. We observed a 0.9% complication rate among all the participants. Conclusions The fundamental importance and consequence of early cancer detection and removal of premalignant adenomatous polyps has been shown to prevent death due to colorectal cancer and to reduce colorectal cancer incidence. Screening by colonoscopy with polypectomy can be an excellent and safe procedure with good levels of acceptability and high level yield for advanced colorectal neoplasia.

Diagnosis of colon cancer using frequency domain fluorescence imaging technique

Early detection and treatment of colon cancer has been associated with better disease prognosis. Conventional and reported optical techniques have limitations in detecting early stages of colon cancer growth. In this paper, a homodyne signal processing assisted frequency domain (FD) fluorescence imaging methodology is proposed for the early diagnosis of colon cancer. Simulated phantom tissues representing the biopsy samples at different stages of colon cancer growth are prepared and used for the imaging study. Selective imaging of healthy and diseased sites simulated in the samples was achieved even for fluorescence emissions having close lifetimes and wavelength values. Possible extension of the methodology for in vivo investigations is also discussed.

Evaluation of telomerase mRNA (hTERT) in colon cancer.

Telomerase activation, a cardinal requirement for immortalization, is a crucial step in the development of malignancy and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene. By reverse transcription-PCR, using primers within the reverse transcriptase domain of hTERT, we investigated telomerase messenger in 8 adenomatous and 9 dysplastic polyps, and in 32 paired cancer-normal mucosa specimens, one liver and one spleen metastasis from patients resected for sporadic colorectal cancer. Telomerase messenger was absent or very low in normal mucosa and in adenomatous polyps. Dysplastic polyps and adenocarcinoma samples showed hTERT mRNA, with higher levels in cancer tissues compared to dysplastic lesions. A high telomerase messenger level was shown to be associated with late-staged cancers and with metastasis; thus, detection of telomerase messenger may be useful in the early diagnosis of colon cancer, and telomerase may be a new target for therapeutic intervention.

Early Diagnosis of Colon Cancer in Ulcerative Colitis

Early Diagnosis of Colon Cancer in Ulcerative Colitis