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Kim J, Dai HD, Michaud T, Verma S, King KM, Ewing JW, Mabiala-Maye G, Estabrooks P. Leveraging Multi-Sectoral Partnership for Colorectal Cancer Education and Screening in the African American Community: A Protocol and Preliminary Results. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2025; 40:248-255. [PMID: 39313626 PMCID: PMC11978712 DOI: 10.1007/s13187-024-02506-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/10/2024] [Indexed: 09/25/2024]
Abstract
Colorectal cancer (CRC) awareness and screening rates are still low in African Americans (AAs), especially for those who do not have regular access to health care. We established a multi-sector community partnership between academia, health system, cancer advocacy, and local county treasurer's office (CTO), to test a pilot CRC screening intervention using a tailored educational brochure and fecal immunochemical test (FIT). Participants were recruited at a local CTO in an urban midwestern region. Once eligible, participants were assigned to 2-by-2 intervention arms by educational strategy (brochure vs. no brochure) and FIT provision strategy (direct provision by onsite staff vs. indirect provision via phone/online request). We compared the effect of different strategies on FIT return rates. Of 1500 individuals approached, 212 were eligible for the study. The final sample consisted of 209 participants who were predominantly men (57%) and AAs (85%). No differences were found in the return rates by educational brochure (24% [brochure] vs. 23% [no brochure]; p = 0.82). In regard to FIT provision strategy, direct FIT provision yielded higher return rates than indirect provision (31% vs. 15%; p = 0.01). When the four groups were compared, direct provision with education brochure yielded the highest return rates (33.9%), followed by direct provision only (27.5%), indirect provision only (18%), and indirect provision with a brochure (12.2%). For community-based CRC screening intervention using stool-based test, the direct provision of FIT kits with educational brochure outperforms the other three strategies.
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Affiliation(s)
- Jungyoon Kim
- Department of Health Services Research and Administration, College of Public Health, University of Nebraska Medical Center, 984350 Nebraska Medical Center, Omaha, NE, 68198, USA.
| | - Hongying Daisy Dai
- Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Tzeyu Michaud
- Department of Health Promotion, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sachi Verma
- Nebraska Hospital Association, Lincoln, NE, USA
| | - Keyonna M King
- Department of Health Promotion, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA
| | | | - Grace Mabiala-Maye
- Department of Health Services Research and Administration, College of Public Health, University of Nebraska Medical Center, 984350 Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Paul Estabrooks
- Department of Health and Kinesiology, University of Utah College of Health, Salt Lake City, UT, USA
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Xu M, Yang JY, Meng T. Effectiveness of colonoscopy, immune fecal occult blood testing, and risk-graded screening strategies in colorectal cancer screening. World J Gastrointest Surg 2024; 16:2270-2280. [PMID: 39087098 PMCID: PMC11287692 DOI: 10.4240/wjgs.v16.i7.2270] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/15/2024] [Accepted: 05/27/2024] [Indexed: 07/22/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common malignant tumors, and early screening is crucial to improving the survival rate of patients. The combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC screening. Colonoscopy and fecal occult blood tests, when combined, can improve screening accuracy and early detection rates, thereby facilitating early intervention and treatment. However, certain risks and costs accompany it, making the establishment of a risk classification model crucial for accurate classification and management of screened subjects. AIM To evaluate the feasibility and effectiveness of colonoscopy, immune fecal occult blood test (FIT), and risk-graded screening strategies in CRC screening. METHODS Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023, participants who met the requirements were randomly assigned to a colonoscopy group, an FIT group, or a graded screening group at a ratio of 1:2:2 (after risk assessment, the high-risk group received colonoscopy, the low-risk group received an FIT test, and the FIT-positive group received colonoscopy). The three groups received CRC screening with different protocols, among which the colonoscopy group only received baseline screening, and the FIT group and the graded screening group received annual follow-up screening based on baseline screening. The primary outcome was the detection rate of advanced tumors, including CRC and advanced adenoma. The population participation rate, advanced tumor detection rate, and colonoscopy load of the three screening programs were compared. RESULTS A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled, including 8082 males (41.7%) and 11291 females (58.3%). The mean age was 60.05 ± 6.5 years. Among them, 3883 patients were enrolled in the colonoscopy group, 7793 in the FIT group, and 7697 in the graded screening group. Two rounds of follow-up screening were completed in the FIT group and the graded screening group. The graded screening group (89.2%) and the colonoscopy group (42.3%) had the lowest overall screening participation rates, while the FIT group had the highest (99.3%). The results of the intentional analysis showed that the detection rate of advanced tumors in the colonoscopy group was greater than that of the FIT group [2.76% vs 2.17%, odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.65, P = 0.037]. There was no significant difference in the detection rate of advanced tumors between the colonoscopy group and the graded screening group (2.76% vs 2.35%, OR = 1.9, 95%CI: 0.93-1.51, P = 0.156), as well as between the graded screening group and the FIT group (2.35% vs 2.17%, OR = 1.09%, 95%CI: 0.88-1.34, P = 0.440). The number of colonoscopy examinations required for each patient with advanced tumors was used as an index to evaluate the colonoscopy load during population screening. The graded screening group had the highest colonoscopy load (15.4 times), followed by the colonoscopy group (10.2 times), and the FIT group had the lowest (7.8 times). CONCLUSION A hierarchical screening strategy based on CRC risk assessment is feasible for screening for CRC in the population. It can be used as an effective supplement to traditional colonoscopy and FIT screening programs.
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Affiliation(s)
- Ming Xu
- Department of Colorectal Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Qingdao 266000, Shandong Province, China
| | - Jing-Yi Yang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Tao Meng
- Department of Colorectal Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Qingdao 266000, Shandong Province, China
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Wang ZM, Pan SP, Zhang JJ, Zhou J. Prediction and analysis of albumin-bilirubin score combined with liver function index and carcinoembryonic antigen on liver metastasis of colorectal cancer. World J Gastrointest Surg 2024; 16:1670-1680. [PMID: 38983332 PMCID: PMC11230030 DOI: 10.4240/wjgs.v16.i6.1670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 04/13/2024] [Accepted: 04/26/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignant tumor, and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients' survival rate and quality of life. Indicators such as albumin bilirubin (ALBI) score, liver function index, and carcinoembryonic antigen (CEA) have shown some potential in the prediction of liver metastasis but have not been fully explored. AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI, liver function index, and CEA, and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance. METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1. The risk factors for liver metastasis in patients with CRC were analyzed, a prediction model was constructed by least absolute shrinkage and selection operator (LASSO) logistic regression, internal validation was performed by the bootstrap method, the reliability of the prediction model was evaluated by subject-work characteristic curves, calibration curves, and clinical decision curves, and a column graph was drawn to show the prediction results. RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria. Through LASSO regression variable screening and logistic regression analysis. The ALBI score, alanine aminotransferase (ALT), and CEA were found to be independent predictors of liver metastases in CRC patients [odds ratio (OR) = 8.062, 95% confidence interval (CI): 2.545-25.540], (OR = 1.037, 95%CI: 1.004-1.071) and (OR = 1.025, 95%CI: 1.008-1.043). The area under the receiver operating characteristic curve (AUC) for the combined prediction of CRLM in the modeling group was 0.921, with a sensitivity of 78.0% and a specificity of 95.0%. The H-index was 0.921, and the H-L fit curve had χ2 = 0.851, a P value of 0.654, and a slope of the calibration curve approaching 1. This indicates that the model is extremely accurate, and the clinical decision curve demonstrates that it can be applied effectively in the real world. We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method. The AUC was 0.913, while the accuracy was 0.869 and the kappa consistency was 0.709. The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918, sensitivity of 85.0%, specificity of 95.6%, C-index of 0.918, and an H-L fitting curve with χ 2 = 0.586, P = 0.746. CONCLUSION The ALBI score, ALT level, and CEA level have a certain value in predicting liver metastasis in patients with CRC. These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC. The risk prediction model developed in this work shows great potential for practical application.
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Affiliation(s)
- Zhan-Mei Wang
- Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College Medicine, Shandong University, Qingdao 266000, Shandong Province, China
| | - Shu-Ping Pan
- Department of Gastroenterology, Feicheng People’s Hospital, Feicheng 271600, Shandong Province, China
| | - Jing-Jing Zhang
- Department of Anus and Intestine Surgery, Xiangya Hospital of Central South University, Changsha 410008, Hunan Province, China
| | - Jun Zhou
- Department of Oncology, Qilu Hospital (Qingdao), Cheeloo College Medicine, Shandong University, Qingdao 266000, Shandong Province, China
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Safarpour H, Ranjbaran J, Erfanian N, Nomiri S, Derakhshani A, Gerarduzzi C, Miraki Feriz A, HosseiniGol E, Saghafi S, Silvestris N. Holistic exploration of CHGA and hsa-miR-137 in colorectal cancer via multi-omic data Integration. Heliyon 2024; 10:e27046. [PMID: 38495181 PMCID: PMC10943347 DOI: 10.1016/j.heliyon.2024.e27046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 12/14/2023] [Accepted: 02/22/2024] [Indexed: 03/19/2024] Open
Abstract
Colorectal cancer (CRC) ranks among the most widespread malignancies globally, with early detection significantly influencing prognosis. Employing a systems biology approach, we aimed to unravel the intricate mRNA-miRNA network linked to CRC pathogenesis, potentially yielding diagnostic biomarkers. Through an integrative analysis of microarray, Bulk RNA-seq, and single-cell RNA-seq data, we explored CRC-related transcriptomes comprehensively. Differential gene expression analysis uncovered crucial genes, while Weighted Gene Co-expression Network Analysis (WGCNA) identified key modules closely linked to CRC. Remarkably, CRC manifested its strongest correlation with the turquoise module, signifying its pivotal role. From the cohort of genes showing high Gene Significance (GS) and Module Membership (MM), and Differential Expression Genes (DEGs), we highlighted the downregulated Chromogranin A (CHGA) as a notable hub gene in CRC. This finding was corroborated by the Human Protein Atlas database, which illustrated decreased CHGA expression in CRC tissues. Additionally, CHGA displayed elevated expression in primary versus metastatic cell lines, as evidenced by the CCLE database. Subsequent RT-qPCR validation substantiated the marked downregulation of CHGA in CRC tissues, reinforcing the significance of our differential expression analysis. Analyzing the Space-Time Gut Cell Atlas dataset underscored specific CHGA expression in epithelial cell subclusters, a trend persisting across developmental stages. Furthermore, our scrutiny of colon and small intestine Enteroendocrine cells uncovered distinct CHGA expression patterns, accentuating its role in CRC pathogenesis. Utilizing the WGCNA algorithm and TargetScan database, we validated the downregulation of hsa-miR-137 in CRC, and integrated assessment highlighted its interplay with CHGA. Our findings advocate hsa-miR-137 and CHGA as promising CRC biomarkers, offering valuable insights into diagnosis and prognosis. Despite proteomic analysis yielding no direct correlation, our multifaceted approach contributes comprehensive understanding of CRC's intricate regulatory mechanisms. In conclusion, this study advances hsa-miR-137 and CHGA as promising CRC biomarkers through an integrated analysis of diverse datasets and network interactions.
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Affiliation(s)
- Hossein Safarpour
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Javad Ranjbaran
- Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Nafiseh Erfanian
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Samira Nomiri
- Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Afshin Derakhshani
- Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124, Bari, Italy
| | - Casimiro Gerarduzzi
- Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada
- Département de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Adib Miraki Feriz
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Edris HosseiniGol
- Department of Computer Engineering, University of Birjand, Birjand, Iran
| | - Samira Saghafi
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Department of Internal Medicine, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, Messina, Italy
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Nagainallur Ravichandran S, Das D, Dayananda EK, Dey A, Banerjee A, Sun-Zhang A, Zhang H, Sun XF, Pathak S. A Review on Emerging Techniques for Diagnosis of Colorectal Cancer. Cancer Invest 2024; 42:119-140. [PMID: 38404236 DOI: 10.1080/07357907.2024.2315443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 02/02/2024] [Indexed: 02/27/2024]
Abstract
Common detection methods in practice for diagnosing colorectal cancer (CRC) are painful and invasive leading to less participation of individuals for CRC diagnosis. Whereas, improved or enhanced imaging systems and other minimally invasive techniques with shorter detection times deliver greater detail and less discomfort in individuals. Thus, this review is a summary of the diagnostic tests, ranging from the simple potential use in developing a flexible CRC treatment to the patient's potential benefits in receiving less invasive procedures and the advanced treatments that might provide a better assessment for the diagnosis of CRC and reduce the mortality related to CRC.
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Affiliation(s)
- Shruthi Nagainallur Ravichandran
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Diptimayee Das
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Erica Katriel Dayananda
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Amit Dey
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Antara Banerjee
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Alexander Sun-Zhang
- Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Stockholm, Sweden
| | - Hong Zhang
- Faculty of Medicine and Health, School of Medical Sciences, Orebro University, Örebro, Sweden
| | - Xiao-Feng Sun
- Division of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Surajit Pathak
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
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Kumarasamy G, Mohd Salim NH, Mohd Afandi NS, Hazlami Habib MA, Mat Amin ND, Ismail MN, Musa M. Glycoproteomics-based liquid biopsy: translational outlook for colorectal cancer clinical management in Southeast Asia. Future Oncol 2023; 19:2313-2332. [PMID: 37937446 DOI: 10.2217/fon-2023-0704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023] Open
Abstract
Colorectal cancer (CRC) signifies a significant healthcare challenge in Southeast Asia. Despite advancements in screening approaches and treatment modalities, significant medical gaps remain, ranging from prevention and early diagnosis to determining targeted therapy and establishing personalized approaches to managing CRC. There is a need to expand more validated biomarkers in clinical practice. An advanced technique incorporating high-throughput mass spectrometry as a liquid biopsy to unravel a repertoire of glycoproteins and glycans would potentially drive the development of clinical tools for CRC screening, diagnosis and monitoring, and it can be further adapted to the existing standard-of-care procedure. Therefore this review offers a perspective on glycoproteomics-driven liquid biopsy and its potential integration into the clinical care of CRC in the southeast Asia region.
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Affiliation(s)
- Gaayathri Kumarasamy
- Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Pulau Pinang, 11800, Malaysia
| | - Nurul Hakimah Mohd Salim
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia
| | - Nur Syafiqah Mohd Afandi
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Mohd Afiq Hazlami Habib
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Nor Datiakma Mat Amin
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
- Nature Products Division, Forest Research Institute Malaysia, Kepong, Selangor, 52109, Malaysia
| | - Mohd Nazri Ismail
- Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Pulau Pinang, 11800, Malaysia
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Marahaini Musa
- Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia
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He Y, Xu T, Fang J, Tong L, Gao W, Zhang Y, Wang Y, Xu Y, Shi S, Liu S, Jin L. Trends in colorectal cancer screening in the United States, 2012 to 2020. J Med Screen 2023; 30:125-133. [PMID: 37157812 DOI: 10.1177/09691413231174163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
OBJECTIVES Despite recommendations to increase the uptake of colorectal cancer (CRC) screening, trends in CRC screening vary with sociodemographic status. We aimed to evaluate trends in CRC screening in the US population and subpopulations. METHODS A total of 1,082,924 participants aged 50 to 75 from five cycles (2012, 2014, 2016, 2018, and 2020) of the Behavioral Risk Factor Surveillance System were involved. Multivariable logistic regression models were performed to evaluate linear trends in CRC screening utilization from 2012 to 2018. Rao-Scott chi-square tests were used to assess the differences in CRC screening utilization between 2018 and 2020. RESULTS The estimated percentage reporting up-to-date with CRC screening increased significantly (P for trend <0.001), from 62.8% (95% CI, 62.4%-63.2%) in 2012 to 66.7% (95% CI, 66.3%-67.2%) in 2018 and 70.4% (95% CI, 69.8%-71.0%) in 2020, in accordance with 2008 US Preventive Services Task Force recommendations. Trends followed similar patterns in most subgroups, although with different magnitudes in several subgroups, primarily those underweight showed a stable percentage over time (P for trend = 0.170). In 2020, 72.4% of participants reported they were up to date with CRC screening, including the utilization of stool DNA tests and virtual colonoscopy. Colonoscopy was the most commonly used test in 2020 (64.5%), followed by FOBT (12.6%), stool DNA test (5.8%), sigmoidoscopy (3.8%), and virtual colonoscopy (2.7%). CONCLUSIONS In this nationally representative survey of the US population from 2012 through 2020, the percentage reporting up to date with CRC screening has increased, but not equally among all subgroups.
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Affiliation(s)
- Yue He
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Tong Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Jiaxin Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Li Tong
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Wenhui Gao
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yuan Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yanfang Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yan Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Shunyao Shi
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Siyu Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Lina Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
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Stürzlinger H, Conrads-Frank A, Eisenmann A, Invansits S, Jahn B, Janzic A, Jelenc M, Kostnapfel T, Mencej Bedrac S, Mühlberger N, Siebert U, Sroczynski G, European Network for Health Technology Assessment (EUnetHTA). Stool DNA testing for early detection of colorectal cancer: systematic review using the HTA Core Model ® for Rapid Relative Effectiveness Assessment. GERMAN MEDICAL SCIENCE : GMS E-JOURNAL 2023; 21:Doc06. [PMID: 37426885 PMCID: PMC10326527 DOI: 10.3205/000320] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Indexed: 07/11/2023]
Abstract
Background Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population. Methods The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE. Results We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma. Conclusions ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.
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Affiliation(s)
| | - Annette Conrads-Frank
- Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
| | | | | | - Beate Jahn
- Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
| | - Andrej Janzic
- Agency for Medicinal Products and Medical Devices of the Republic of Slovenia (JAZMP), Ljubljana, Slovenia
| | - Marjetka Jelenc
- National Institute of Public Health (NIJZ), Ljubljana, Slovenia
| | | | - Simona Mencej Bedrac
- Agency for Medicinal Products and Medical Devices of the Republic of Slovenia (JAZMP), Ljubljana, Slovenia
| | - Nikolai Mühlberger
- Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
| | - Uwe Siebert
- Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
| | - Gaby Sroczynski
- Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
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Zhang X, Hou H, Jiang M, Zhang X. Aberrant circulating tumor DNA methylation and exosomal microRNA biomarkers for early detection of colorectal cancer. Mol Biol Rep 2023; 50:2743-2750. [PMID: 36583782 DOI: 10.1007/s11033-022-08194-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 12/06/2022] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis. Research progress in liquid biopsy has led to the finding that circulating tumor-derived DNA (ctDNA) and exosomes play vital roles in early detection of CRC. THE APPLICATIONS OF LIQUID BIOPSY FOR EARLY DETECTION OF COLORECTAL CANCER: Moreover, the increased understanding of epigenetics has highlighted the role of ctDNA methylation in CRC carcinogenesis, and the detection of aberrant ctDNA methylation markers is a feasible strategy for diagnosis of early-stage CRC. Among exosomal markers, microRNAs (miRNAs) are abundant and are the most researched. Upregulated or downregulated expression of exosome-derived miRNAs can indicate the occurrence of early-stage CRC. FUTURE PERSPECTIVE The current research progress on aberrant ctDNA methylation and tumor exosomal miRNA biomarkers in early detection of CRC is summarized in this review, and the advantages and shortcomings of the methods are discussed.
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Affiliation(s)
- Xuchen Zhang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Helei Hou
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Man Jiang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Xiaochun Zhang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China. .,Qingdao Cancer Institute, Qingdao University, Qingdao, China.
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10
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Chen YN, Shih CY, Guo SL, Liu CY, Shen MH, Chang SC, Ku WC, Huang CC, Huang CJ. Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens. Biomed Rep 2023; 18:22. [PMID: 36846616 PMCID: PMC9945078 DOI: 10.3892/br.2023.1604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/20/2022] [Indexed: 02/10/2023] Open
Abstract
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.
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Affiliation(s)
- Yu-Nung Chen
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Cheng-Yen Shih
- Division of Gastroenterology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Shu-Lin Guo
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Anesthesiology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C,Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan, R.O.C
| | - Chih-Yi Liu
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan, R.O.C
| | - Ming-Hung Shen
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Surgery, Fu Jen Catholic University Hospital, New Taipei 24352, Taiwan, R.O.C.,PhD Program in Nutrition and Food Science, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Shih-Chang Chang
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Wei-Chi Ku
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Chi-Cheng Huang
- Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10090, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
| | - Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.,Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
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11
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Ranjbaran J, Safarpour H, Nomiri S, Tavakoli T, Rezaei Z, Salmani F, Larki P, Chamani E. Experimental validation of in silico analysis estimated the reverse effect of upregulated
hsa‐miR
‐106a‐5p and
hsa‐miR
‐223‐3p on
SLC4A4
gene expression in Iranian patients with colorectal adenocarcinoma by
RT‐qPCR. Cancer Med 2022; 12:7005-7018. [PMID: 36468451 PMCID: PMC10067115 DOI: 10.1002/cam4.5499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 11/07/2022] [Accepted: 11/19/2022] [Indexed: 12/10/2022] Open
Abstract
BACKGROUND AND METHODS Colorectal cancer (CRC) is considered one of the most common malignancies worldwide. The diagnosis and prognosis of the patients are very poor. In this study, we used in-silico analysis and experimental techniques to investigate novel co-expression genes and their associated miRNA networks in CRC. For this purpose, we conducted a comprehensive transcriptome analysis using online bulk and single-cell RNA-seq datasets. We then validated the results on tissue samples from cancerous and adjacent normal tissues from CRC patients by RT-qPCR. RESULTS Using a weighted gene co-expression network algorithm, we identified SLC4A4 as a significantly downregulated hub gene in the CRC. The single-cell analysis indicated that the expression level of SLC4A4 in Paneth cells is higher than in other cell populations. Further computational analysis suggested hsa-miR-223-3p and hsa-miR-106a-5p as two specific hub-miRNAs for the SLC4A4 gene. RT-qPCR analysis showed a 2.60-fold downregulation of SLC4A4. Moreover, hsa-miR-223-3p and hsa-miR-106a-5p showed an increased expression level of 5.58-fold and 9.66-fold in CRC samples, respectively. Based on the marginal model analysis, by increasing the expression of hsa-miR-106a-5p, the average expression of the SLC4A4 gene significantly decreased by 103 units. Furthermore, ROC curves analysis indicated statistically significant for diagnostic ability of SLC4A4 (AUC: 0.94, Sensitivity: 95.5%, Specificity: 95.5%) and hsa-miR-106a-5p (AUC: 0.72, Sensitivity: 72.7%, Specificity: 100%). CONCLUSION This study provides a framework of co-expression gene modules and miRNAs of CRC, which identifies some important biomarkers for CRC pathogenicity and diagnosis. Further experimental evidence will be required to support this study and validate the precise molecular pathways.
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Affiliation(s)
- Javad Ranjbaran
- Department of Clinical Biochemistry, School of Medicine Birjand University of Medical Sciences Birjand Iran
| | - Hossein Safarpour
- Cellular and Molecular Research Center Birjand University of Medical Sciences Birjand Iran
| | - Samira Nomiri
- Department of Clinical Biochemistry, School of Medicine Birjand University of Medical Sciences Birjand Iran
| | - Tahmine Tavakoli
- Department of Internal Medicine, School of Medicine Birjand University of Medical Sciences Birjand Iran
| | - Zohreh Rezaei
- Department of Biology, Faculty of Sciences University of Sistan and Balouchestan Zahedan Iran
| | - Fatemeh Salmani
- Department of Epidemiology and Biostatistics, Social Determinants of Health Research Center, Faculty of Health Birjand University of Medical Sciences Birjand Iran
| | - Pegah Larki
- Department of Molecular Genetics, Genomic Research Center Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Elham Chamani
- Department of Clinical Biochemistry, School of Medicine Birjand University of Medical Sciences Birjand Iran
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12
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Sattar RSA, Verma R, Nimisha, Kumar A, Dar GM, Apurva, Sharma AK, Kumari I, Ahmad E, Ali A, Mahajan B, Saluja SS. Diagnostic and prognostic biomarkers in colorectal cancer and the potential role of exosomes in drug delivery. Cell Signal 2022; 99:110413. [PMID: 35907519 DOI: 10.1016/j.cellsig.2022.110413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/13/2022] [Accepted: 07/15/2022] [Indexed: 11/03/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer with the second most frequent cause of death worldwide. One fourth to one fifth of the CRC cases are detected at advance stage. Early detection of colorectal cancer might help in decreasing mortality and morbidity worldwide. CRC being a heterogeneous disease, new non-invasive approaches are needed to complement and improve the screening and management of CRC. Reliable and early detectable biomarkers would improve diagnosis, prognosis, therapeutic responses, and will enable the prediction of drug response and recurrence risk. Over the past decades molecular research has demonstrated the potentials of CTCs, ctDNAs, circulating mRNAs, ncRNAs, and exosomes as tumor biomarkers. Non-invasive screening approaches using fecal samples for identification of altered gut microbes in CRC is also gaining attention. Exosomes can be potential candidates that can be employed in the drug delivery system. Further, the integration of in vitro, in vivo and in silico models that involve CRC biomarkers will help to understand the interactions occurring at the cellular level. This review summarizes recent update on CRC biomarkers and their application along with the nanoparticles followed by the application of organoid culture in CRC.
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Affiliation(s)
- Real Sumayya Abdul Sattar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Renu Verma
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Nimisha
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Arun Kumar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Ghulam Mehdi Dar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Apurva
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Abhay Kumar Sharma
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Indu Kumari
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Ejaj Ahmad
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Asgar Ali
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Bhawna Mahajan
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India; Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Sundeep Singh Saluja
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India; Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India.
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13
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Game-theoretic link relevance indexing on genome-wide expression dataset identifies putative salient genes with potential etiological and diapeutics role in colorectal cancer. Sci Rep 2022; 12:13409. [PMID: 35927308 PMCID: PMC9352798 DOI: 10.1038/s41598-022-17266-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 07/22/2022] [Indexed: 11/08/2022] Open
Abstract
Diapeutics gene markers in colorectal cancer (CRC) can help manage mortality caused by the disease. We applied a game-theoretic link relevance Index (LRI) scoring on the high-throughput whole-genome transcriptome dataset to identify salient genes in CRC and obtained 126 salient genes with LRI score greater than zero. The biomarkers database lacks preliminary information on the salient genes as biomarkers for all the available cancer cell types. The salient genes revealed eleven, one and six overrepresentations for major Biological Processes, Molecular Function, and Cellular components. However, no enrichment with respect to chromosome location was found for the salient genes. Significantly high enrichments were observed for several KEGG, Reactome and PPI terms. The survival analysis of top protein-coding salient genes exhibited superior prognostic characteristics for CRC. MIR143HG, AMOTL1, ACTG2 and other salient genes lack sufficient information regarding their etiological role in CRC. Further investigation in LRI methodology and salient genes to augment the existing knowledge base may create new milestones in CRC diapeutics.
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14
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Jiang HH, Xing SW, Tang X, Chen Y, Lin K, He LW, Lin MB, Tang EJ. Novel multiplex stool-based assay for the detection of early-stage colon cancer in a Chinese population. World J Gastroenterol 2022; 28:2705-2732. [PMID: 35979157 PMCID: PMC9260868 DOI: 10.3748/wjg.v28.i24.2705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/14/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Stool DNA (sDNA) methylation analysis is a promising, noninvasive approach for colorectal cancer screening; however, reliable biomarkers for detecting early-stage colon cancer (ECC) are lacking, particularly in the Chinese population.
AIM To identify a novel stool-based assay that can improve the effectiveness of ECC screening.
METHODS A blinded case-control study was performed using archived stool samples from 125 ECC patients, and 125 control subjects with normal colonoscopy. The cohort was randomly divided into training and test sets at a 1.5:1 ratio. Targeted bisulfite sequencing (TBSeq) was conducted on five pairs of preoperative and postop-erative sDNA samples from ECC patients to identify DNA methylation biomarkers, which were validated using pyrosequencing. By logistic regression analysis, a multiplex stool-based assay was developed in the training set, and the detection performance was further assessed in the test set and combined set. The χ2 test was used to investigate the association of detection sensitivity with clinico-pathological features.
RESULTS Following TBSeq, three hypermethylated cytosine-guanine sites were selected as biomarkers, including paired box 8, Ras-association domain family 1 and secreted frizzled-related protein 2, which differed between the groups and were involved in important cancer pathways. An sDNA panel containing the three biomarkers was constructed with a logistic model. Receiver operating characteristic (ROC) analysis revealed that this panel was superior to the fecal immunochemical test (FIT) or serum carcinoembryonic antigen for the detection of ECC. We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness. In the combined set, the sensitivity, specificity and area under the ROC curve for this multiplex assay were 80.0%, 93.6% and 0.918, respectively, and the performance remained excellent in the subgroup analysis by tumor stage. In addition, the detection sensitivity did not differ with tumor site, tumor stage, histological differentiation, age or sex, but was significantly higher in T4 than in T1-3 stage tumors (P = 0.041).
CONCLUSION We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT, which could detect ECC with high sensitivity and specificity throughout the colon, showing a promising application perspective.
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Affiliation(s)
- Hui-Hong Jiang
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
| | - Si-Wei Xing
- Department of Urology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Xuan Tang
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Ying Chen
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Kang Lin
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Lu-Wei He
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Mou-Bin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
| | - Er-Jiang Tang
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University, Shanghai 200090, China
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15
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Koppad S, Basava A, Nash K, Gkoutos GV, Acharjee A. Machine Learning-Based Identification of Colon Cancer Candidate Diagnostics Genes. BIOLOGY 2022; 11:biology11030365. [PMID: 35336739 PMCID: PMC8944988 DOI: 10.3390/biology11030365] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 02/16/2022] [Accepted: 02/23/2022] [Indexed: 01/27/2023]
Abstract
Simple Summary We developed a predictive approach using different machine learning methods to identify a number of genes that can potentially serve as novel diagnostic colon cancer biomarkers. Abstract Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death and the fourth most commonly diagnosed cancer worldwide. Due to a lack of diagnostic biomarkers and understanding of the underlying molecular mechanisms, CRC’s mortality rate continues to grow. CRC occurrence and progression are dynamic processes. The expression levels of specific molecules vary at various stages of CRC, rendering its early detection and diagnosis challenging and the need for identifying accurate and meaningful CRC biomarkers more pressing. The advances in high-throughput sequencing technologies have been used to explore novel gene expression, targeted treatments, and colon cancer pathogenesis. Such approaches are routinely being applied and result in large datasets whose analysis is increasingly becoming dependent on machine learning (ML) algorithms that have been demonstrated to be computationally efficient platforms for the identification of variables across such high-dimensional datasets. Methods: We developed a novel ML-based experimental design to study CRC gene associations. Six different machine learning methods were employed as classifiers to identify genes that can be used as diagnostics for CRC using gene expression and clinical datasets. The accuracy, sensitivity, specificity, F1 score, and area under receiver operating characteristic (AUROC) curve were derived to explore the differentially expressed genes (DEGs) for CRC diagnosis. Gene ontology enrichment analyses of these DEGs were performed and predicted gene signatures were linked with miRNAs. Results: We evaluated six machine learning classification methods (Adaboost, ExtraTrees, logistic regression, naïve Bayes classifier, random forest, and XGBoost) across different combinations of training and test datasets over GEO datasets. The accuracy and the AUROC of each combination of training and test data with different algorithms were used as comparison metrics. Random forest (RF) models consistently performed better than other models. In total, 34 genes were identified and used for pathway and gene set enrichment analysis. Further mapping of the 34 genes with miRNA identified interesting miRNA hubs genes. Conclusions: We identified 34 genes with high accuracy that can be used as a diagnostics panel for CRC.
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Affiliation(s)
- Saraswati Koppad
- Department of Computer Science and Engineering, National Institute of Technology Karnataka, Mangalore 575025, India; (S.K.); (A.B.)
| | - Annappa Basava
- Department of Computer Science and Engineering, National Institute of Technology Karnataka, Mangalore 575025, India; (S.K.); (A.B.)
| | - Katrina Nash
- College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK;
| | - Georgios V. Gkoutos
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK;
- Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TT, UK
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham B15 2WB, UK
- MRC Health Data Research UK (HDR UK), Midlands Site, Birmingham B15 2TT, UK
- NIHR Experimental Cancer Medicine Centre, Birmingham B15 2TT, UK
- NIHR Biomedical Research Centre, University Hospital Birmingham, Birmingham B15 2TT, UK
| | - Animesh Acharjee
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK;
- Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TT, UK
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospital Birmingham, Birmingham B15 2WB, UK
- Correspondence: ; Tel.: +44-07403642022
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16
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Nomiri S, Hoshyar R, Chamani E, Rezaei Z, Salmani F, Larki P, Tavakoli T, Gholipour F, Tabrizi NJ, Derakhshani A, Santarpia M, Franchina T, Brunetti O, Silvestris N, Safarpour H. Prediction and validation of GUCA2B as the hub-gene in colorectal cancer based on co-expression network analysis: In-silico and in-vivo study. Biomed Pharmacother 2022; 147:112691. [PMID: 35151227 DOI: 10.1016/j.biopha.2022.112691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/25/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Several serious attempts to treat colorectal cancer have been made in recent decades. However, no effective treatment has yet been discovered due to the complexities of its etiology. METHODS we used Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules, hub-genes, and mRNA-miRNA regulatory networks associated with CRC. Next, enrichment analysis of modules has been performed using Cluepedia. Next, quantitative real-time PCR (RT-qPCR) was used to validate the expression of selected hub-genes in CRC tissues. RESULTS Based on the WGCNA results, the brown module had a significant positive correlation (r = 0.98, p-value=9e-07) with CRC. Using the survival and DEGs analyses, 22 genes were identified as hub-genes. Next, three candidate hub-genes were selected for RT-qPCR validation, and 22 pairs of cancerous and non-cancerous tissues were collected from CRC patients referred to the Gastroenterology and Liver Clinic. The RT-qPCR results revealed that the expression of GUCA2B was significantly reduced in CRC tissues, which is consistent with the results of differential expression analysis. Finally, top miRNAs correlated with GUCA2B were identified, and ROC analyses revealed that GUCA2B has a high diagnostic performance for CRC. CONCLUSIONS The current study discovered key modules and GUCA2B as a hub-gene associated with CRC, providing references to understand the pathogenesis and be considered a novel candidate to CRC target therapy.
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Affiliation(s)
- Samira Nomiri
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Reyhane Hoshyar
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Elham Chamani
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Zohreh Rezaei
- Department of Biology, Faculty of Sciences, University of Sistan and Balouchestan, Zahedan, Iran
| | - Fatemeh Salmani
- Department of Epidemiology and Biostatistics, Social Determinants of Health Research Center, Faculty of Health, Birjand University of Medical Sciences, Birjand, Iran
| | - Pegah Larki
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tahmine Tavakoli
- Cardiovascular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Faranak Gholipour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Jalili Tabrizi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Afshin Derakhshani
- Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Mariacarmela Santarpia
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Tindara Franchina
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, Bari, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, Bari, Italy; Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari, Bari, Italy.
| | - Hossein Safarpour
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
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17
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Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23020852. [PMID: 35055034 PMCID: PMC8776048 DOI: 10.3390/ijms23020852] [Citation(s) in RCA: 124] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.
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18
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Bhatti U, Jansson-Knodell C, Saito A, Han A, Krajicek E, Han Y, Imperiale TF, Fayad N. Not FIT for Use: Fecal Immunochemical Testing in the Inpatient and Emergency Settings. Am J Med 2022; 135:76-81. [PMID: 34508698 DOI: 10.1016/j.amjmed.2021.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 08/01/2021] [Accepted: 08/12/2021] [Indexed: 11/01/2022]
Abstract
BACKGROUND Fecal immunochemical testing (FIT) is widely used for colorectal cancer screening, its only indication. Its effect on clinical decision-making beyond screening is unknown. We studied the use of FIT in emergency and inpatient settings and its impact on patient care. METHODS Using electronic medical records, we reviewed all non-ambulatory FITs performed from November 2017 to October 2019 at a tertiary care community hospital. We collected data on demographics, indications, gastroenterology consultations, and endoscopic procedures. Multivariate logistic regression was performed to determine the effect of FIT on gastroenterology consultation and endoscopy. RESULTS We identified 550 patients with at least 1 FIT test. Only 3 FITs (0.5%) were performed for colorectal cancer screening. FITs were primarily ordered from the emergency department (45.3%) or inpatient hospital floor (42.2%). Anemia (44.0%), followed by gastrointestinal bleeding (40.9%), were the most common indications. FIT was positive in 253 patients (46.0%), and gastroenterology consultation was obtained for 47.4% (n = 120), compared with 14.5% (n = 43) of the 297 FIT-negative patients (odds ratio 3.28; 95% confidence interval, 2.23-4.82, P < .0001). A potential bleeding source was identified in 80% of patients with reported or witnessed overt gastrointestinal bleeding, a similar proportion (80.7%; P = .92) to patients who were FIT positive with overt gastrointestinal bleeding. Multivariate analysis showed that melena, hematemesis, and a positive FIT were associated with gastroenterology consultation (all P < .05), while only melena (odds ratio 3.34; 95% confidence interval, 1.48-7.54) was associated with endoscopy. CONCLUSIONS Nearly all emergency department and inpatient FIT use was inappropriate. FIT resulted in more gastroenterology consultation but was not independently associated with inpatient endoscopy.
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Affiliation(s)
- Umer Bhatti
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis
| | - Claire Jansson-Knodell
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis
| | - Akira Saito
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis
| | - Andrew Han
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis
| | - Edward Krajicek
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis
| | - Yan Han
- Division of Biostatistics & Health Data Science, Indiana University-Purdue University, Indianapolis
| | - Thomas F Imperiale
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis; Division of Gastroenterology and Hepatology, Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Ind; Regenstrief Institute, Inc. Indianapolis, Ind
| | - Nabil Fayad
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University, Indianapolis; Division of Gastroenterology and Hepatology, Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Ind.
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DNM1: A Prognostic Biomarker Associated with Immune Infiltration in Colon Cancer-A Study Based on TCGA Database. BIOMED RESEARCH INTERNATIONAL 2021; 2021:4896106. [PMID: 34888380 PMCID: PMC8651384 DOI: 10.1155/2021/4896106] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/02/2021] [Indexed: 12/15/2022]
Abstract
Aim The aim of our work was to determine the utility of DNM1 as a biomarker for the diagnosis and prognosis of colon cancer (CC). Methods DNM1 expression variations in CC vs. normal tissues were investigated using The Cancer Genome Atlas (TCGA) database. The association of DNM1 expression levels with the clinicopathological variables in CC prognosis was investigated using logistic regression analyses. Independent prognostic factors for CC were evaluated using univariate and multivariate Cox regression analyses. The correlation between DNM1 expression and immune cell infiltration was estimated using single-sample Gene Set Enrichment Analysis (ssGSEA). Results DNM1 expression in CC tissues was significantly higher than that in normal tissues. High DNM1 expression was significantly correlated with M stage, N stage, perineural invasion and lymphatic invasion and predicted poor prognosis. The univariate analysis highlighted that DNM1 was an independent CC risk factor. Results of ssGSEA showed that DNM1 was linked to several cancer-related pathways, including the neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, ECM-receptor interaction, dilated cardiomyopathy, and calcium signaling pathway. Moreover, DNM1 expression was positively correlated with the level of infiltration by Neutrophils, Tregs, NK cells, and Macrophages. Conclusion DNM1 has a significant function and has diagnostic and prognostic potential for CC.
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Pei B, Zhang Z, Sun J, Qi X, Cui Q, de Yan Y, Wang X, Yang M, Song C, Yin L, Wu J, Geng Z, Wang YB, Lu Y. Functionalized Ferroferric Oxide Nanomagnetic Beads for Extraction of Nucleic Acid and Its Application in Early Screening of Colorectal Cancer. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:5230666. [PMID: 34900193 PMCID: PMC8654521 DOI: 10.1155/2021/5230666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 08/31/2021] [Accepted: 10/11/2021] [Indexed: 11/17/2022]
Abstract
Early screening is an important way to reduce the incidence and mortality of colorectal cancer (CRC). Fecal DNA testing stands out among many screening methods due to its high sensitivity. However, at this stage, researchers have not found a high-efficiency method for fecal DNA extraction. To this end, this work carried out a new round of exploration. Here, this experiment synthesized a kind of nanomagnetic beads (NH2-SiO2@Fe3O4) with good stability for nucleic acid extraction. A comparative study with the centrifugal adsorption column method revealed the significant advantages of the magnetic bead method in extracting fecal DNA. The DNA extracted by the magnetic bead method is of high purity, can also achieve high-throughput tests, and is more suitable for polymerase chain reaction detection, greatly simplifying the stool DNA detection process and providing a basis for the widespread promotion of early screening.
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Affiliation(s)
- Bing Pei
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Zhenjiang Zhang
- Department of Infectious Diseases, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Jian Sun
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - xiaoYan Qi
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Qian Cui
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - you de Yan
- Department of Infectious Diseases, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - xiaoYan Wang
- Department of Gastroenterology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Miaomiao Yang
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Chunjie Song
- Department of Neurology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Lingsi Yin
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Juan Wu
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Zhixin Geng
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Yue Bang Wang
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
| | - Yi Lu
- Department of Clinical Laboratory, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, Jiangsu, China
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21
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Colorectal Cancer Screening: Have We Addressed Concerns and Needs of the Target Population? GASTROINTESTINAL DISORDERS 2021. [DOI: 10.3390/gidisord3040018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Despite the recognized benefits of colorectal cancer (CRC) screening, uptake is still suboptimal in many countries. In addressing this issue, one important element that has not received sufficient attention is population preference. Our review provides a comprehensive summary of the up-to-date evidence relative to this topic. Four OVID databases were searched: Ovid MEDLINE® ALL, Biological Abstracts, CAB Abstracts, and Global Health. Among the 742 articles generated, 154 full texts were selected for a more thorough evaluation based on predefined inclusion criteria. Finally, 83 studies were included in our review. The general population preferred either colonoscopy as the most accurate test, or fecal occult blood test (FOBT) as the least invasive for CRC screening. The emerging blood test (SEPT9) and capsule colonoscopy (nanopill), with the potential to overcome the pitfalls of the available techniques, were also favored. Gender, age, race, screening experience, education and beliefs, the perceived risk of CRC, insurance, and health status influence one’s test preference. To improve uptake, CRC screening programs should consider offering test alternatives and tailoring the content and delivery of screening information to the public’s preferences. Other logistical measures in terms of the types of bowel preparation, gender of endoscopist, stool collection device, and reward for participants can also be useful.
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Shao X, Wang H, Yu Y, Zhou C. Combined detection of stool-based methylation indicators for early screening of colorectal neoplasm. Am J Transl Res 2021; 13:11597-11607. [PMID: 34786085 PMCID: PMC8581910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 08/13/2021] [Indexed: 06/13/2023]
Abstract
In the past two decades, several methylated DNA targets, including gene promoters and other intronic markers have been explored in tumors and benign lesions. Therefore, it can be expected that a panel of stool-based biomarkers will become a screening method for colorectal cancer (CRC) and adenoma with better sensitivity and specificity, aiming to decrease the incidence and mortality of CRC. In this study, the methylation of secreted frizzled-related protein 1 (SFRP1), hyperplastic polyposis protein 1 (HPP1), α-internexin (INA), Wnt inhibitory factor 1 (WIF1), tissue factor pathway inhibitor 2 (TFPI2), ikaros family zinc finger protein 1 (IKZF1), and spastic paraplegia 20 (SPG20) were detected in stool samples from patients with CRC, adenoma, polyps, and healthy controls, respectively, and these biomarkers were used to establish a logistic regression model for classification. Receiver operating characteristic (ROC) curves were drawn to assess the importance of each biomarker. Subsequently, a biomarker or combination of biomarkers was analyzed for early screening of high-risk neoplasm. The data showed that when a single biomarker was used for CRC screening, the sensitivity ranged from 63.9% to 76.8%, the area under the curve (AUC) ranged from 0.821 to 0.875, and the accuracy ranged from 77.0% to 84.5%. Finally, the methylation of SFRP1, HPP1, TFPI2, and IKZF1 was selected using a backward stepwise method in the multivariate logistic analysis according to the Akaike Information Criterion. These findings indicate that stool DNA biomarkers have good diagnostic power in discriminating high-risk level of neoplasm from healthy population.
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Affiliation(s)
- Xinyu Shao
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Huiyu Wang
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Yang Yu
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
| | - Chunli Zhou
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou, Jiangsu, China
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Wu Y, Zhang J, Yang X, Yin Z, Yang H, Tang T, Chen Z, Tian D, Yang Y, Zhou Z, Lu F. Early Diagnosis of Occult Blood of Colorectal Cancer Based on Nano-Colloidal Gold Sandwich Immunochromatography. J Biomed Nanotechnol 2021; 17:1525-1534. [PMID: 34544530 DOI: 10.1166/jbn.2021.3135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The development of science and technology has deepened people's understanding of cancer, changing the management of malignant tumors in the medical field. Given the common precancerous characteristics of colorectal cancer (CRC), researchers studied early CRC screening. The complexity of traditional diagnostics forced medical staff to speed up CRC innovation early screening methods. Here, we prepared nano-colloidal gold raw materials with different particle sizes (15 and 30 nm) and observed the morphological characteristics and properties of the materials. Simultaneously, the nanocolloidal gold double antibody sandwich kit was designed through the optimum pH value and protein content screening experiment. The results of clinical enteroscopy confirmed the important guiding significance of the equipment in early CRC screening.
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Affiliation(s)
- Yongying Wu
- Laboratory Department, Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Jiaoyan Zhang
- Early Screening of Digestive Tract Tumors in the Department of Gastroenterology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Xiaolin Yang
- Hunan Tumor Hospital Department of Digestive Urology, Changsha 410006, Hunan, PR China
| | - Zou Yin
- Department of Oncology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Hui Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Tao Tang
- Department of Science and Education and Department of Infection, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Zhitao Chen
- Department of Pathology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Dayong Tian
- Department of Gastroenterology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Yixia Yang
- Laboratory Department, Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Zhihua Zhou
- Department of Oncology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
| | - Fangyang Lu
- Department of Oncology, The Second Affiliated Hospital of Guizhou Medical University, Kaili 556000, Guizhou, PR China
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Roy S, Dickey S, Wang HL, Washington A, Polo R, Gwede CK, Luque JS. Systematic Review of Interventions to Increase Stool Blood Colorectal Cancer Screening in African Americans. J Community Health 2021; 46:232-244. [PMID: 32583358 PMCID: PMC7313439 DOI: 10.1007/s10900-020-00867-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
African Americans experience colorectal cancer (CRC) related disparities compared to other racial groups in the United States. African Americans are frequently diagnosed with CRC at a later stage, screening is underutilized, and mortality rates are highest in this group. This systematic review focused on intervention studies using stool blood CRC screening among African Americans in primary care and community settings. Given wide accessibility, low cost, and ease of dissemination of stool-based CRC screening tests, this review aims to determine effective interventions to improve participation rates. This systematic review included intervention studies published between January 1, 2000 and March 16, 2019. After reviewing an initial search of 650 studies, 11 studies were eventually included in this review. The included studies were studies conducted in community and clinical settings, using both inreach and outreach strategies to increase CRC screening. For each study, an unadjusted odds ratio (OR) for the CRC screening intervention compared to the control arm was calculated based on the data in each study to report effectiveness. The eleven studies together recruited a total of 3334 participants. The five studies using two-arm experimental designs ranged in effectiveness with ORs ranging from 1.1 to 13.0 using interventions such as mailed reminders, patient navigation, and tailored educational materials. Effective strategies to increase stool blood testing included mailed stool blood tests augmented by patient navigation, tailored educational materials, and follow-up calls or mailings to increase trust in the patient-provider relationship. More studies are needed on stool blood testing interventions to determine effectiveness in this population.
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Affiliation(s)
- Siddhartha Roy
- Department of Family and Community Medicine, Pennsylvania State University Health Milton S. Hershey Medical Center, Hershey, PA, USA
- Department of Cancer Control, Penn State Cancer Institute, Hershey, PA, USA
| | - Sabrina Dickey
- College of Nursing, Florida State University, Tallahassee, FL, USA
| | - Hsiao-Lan Wang
- College of Nursing, University of South Florida, Tampa, FL, USA
| | - Alexandria Washington
- College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, 1415 South Martin Luther King, Jr. Blvd, Tallahassee, FL, 32307, USA
| | - Randy Polo
- University Libraries, University of South Florida, Tampa, FL, USA
| | - Clement K Gwede
- Division of Population Sciences, Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USA
| | - John S Luque
- College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, 1415 South Martin Luther King, Jr. Blvd, Tallahassee, FL, 32307, USA.
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piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients. Genes (Basel) 2021; 12:genes12040598. [PMID: 33921704 PMCID: PMC8074037 DOI: 10.3390/genes12040598] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/12/2021] [Accepted: 04/17/2021] [Indexed: 12/24/2022] Open
Abstract
Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients’ serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.
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Wang DY, He KX, Huang Y, Lou QQ, He T, Xu X. A New Method for the Detection of Colorectal Cancer and the Precancerous Lesions: Occult Blood Testing Combination with Promoter Methylation in the Fecal Sample. J Cancer 2021; 12:335-342. [PMID: 33391430 PMCID: PMC7738999 DOI: 10.7150/jca.50525] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/24/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Noninvasive stool-based DNA methylation testing emerges as a new approach for detecting colorectal cancer (CRC). However, its feasibility for early detection of CRC and precancerous lesions in the Chinese population remains inconclusive. Methods: In this study, we establish a possibilities screening method (sDNA-FOBT) for detecting CRC and precancerous lesions (hyperplastic polyps [HP] and adenomas [AD]) and evaluate its detection performance in the Chinese population. This method combined a molecular assay of DNA methylation markers (BMP3, NDRG4, and SDC2) with the human hemoglobin test (FOBT) in stool samples. Results: The sensitivity of sDNA-FOBT was 85.42% for CRC, 85.71% for AD, and 28.21% for HP, respectively, at the specificity of 92%. The diagnostic efficacy of sDNA-FOBT for detecting CRC and precancerous lesions was significantly higher than FOBT alone (sensitivity: 61.70% vs. 51.06%, P<0.01; AUC: 0.78 vs. 0.72, P<0.001), especially for CRC (AUC: 0.91 vs. 0.86, P<0.001) and AD (AUC: 0.91 vs. 0.75, P<0.05). No significant difference was observed between the detection sensitivity of sDNA-FOBT and the clinical variables. Notably, compared with FOBT, sDNA-FOBT was more effective in the detection of CRC and precancerous lesions in the patients aged >50 y (62.34% vs 54.55%, P<0.05). Conclusion: Our results demonstrate that sDNA-FOBT is a promising method for screening CRC and precancerous lesions in the Chinese population. Further studies are required to validate the results in a larger sample capacity.
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Affiliation(s)
- Dan-Yang Wang
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Kang-Xin He
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ying Huang
- Department of Clinical Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Qin-Qin Lou
- Hangzhou Youke Biomedical Inc., Hangzhou, China
| | - Ti He
- Shanghai Genechem Clinical Laboratory Inc., Shanghai, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Loktionov A. Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins? World J Gastrointest Oncol 2020; 12:124-148. [PMID: 32104546 PMCID: PMC7031146 DOI: 10.4251/wjgo.v12.i2.124] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 10/30/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a global problem affecting millions of people worldwide. This disease is unique because of its slow progress that makes it preventable and often curable. CRC symptoms usually emerge only at advanced stages of the disease, consequently its early detection can be achieved only through active population screening, which markedly reduces mortality due to this cancer. CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and, in most cases, samples of either stool or blood are used. However, alternative biological substances that can be collected non-invasively (colorectal mucus, urine, saliva, exhaled air) have now emerged as new sources of diagnostic biomarkers. The main categories of currently explored CRC biomarkers are: (1) Proteins (comprising widely used haemoglobin); (2) DNA (including mutations and methylation markers); (3) RNA (in particular microRNAs); (4) Low molecular weight metabolites (comprising volatile organic compounds) detectable by metabolomic techniques; and (5) Shifts in gut microbiome composition. Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied. While some of these studies generated promising early results, very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques. Such DNA-based tests as Food and Drug Administration-approved multitarget stool test (marketed as Cologuard®) or blood test for methylated septin 9 (marketed as Epi proColon® 2.0 CE) show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools. It can be concluded that, despite its deficiencies, the protein (haemoglobin) detection-based faecal immunochemical test (FIT) today presents the most cost-effective option for non-invasive CRC screening. The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening. However, continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.
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Zhou H, Zhu Y, Wei F, Shao Y, Pan J, Wang G, Xu K, Cheng Y. Significance of MUC2 gene methylation detection in pancreatic cancer diagnosis. Pancreatology 2019; 19:1049-1053. [PMID: 31590960 DOI: 10.1016/j.pan.2019.09.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 09/15/2019] [Accepted: 09/27/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE This study was conducted to explore the diagnostic value of MUC2 gene methylation in pancreatic cancer. METHODS Methylation restriction enzyme digestion (Msp I/Hap II) and polymerase chain reaction (PCR) were performed to detect methylation of the MUC2 gene in fecal and blood specimens from seven study subjects with pancreatic cancer (PC), chronic pancreatitis (CP), or normal controls (CON). Simultaneously, blood CA 19-9 levels were detected as a positive indicator of PC. RESULTS MUC2 methylation was detected in 50% of PC cell lines. In fecal samples, the MUC2 methylation rate in PC (n = 30) was 43.3%, which was significantly higher than those in CP (n = 8, 0%, P < 0.05) and CON (n = 20, 5.0%, P < 0.05). In blood samples, the MUC2 methylation rate in PC (n = 40) was 52.5%, which was significantly higher than those in CP (n = 15, 0%, P < 0.01) and CON (n = 25, 4.0%, P < 0.01). For PC diagnosis, MUC2 gene methylation in blood samples showed higher specificity and positive predictive value than CA 19-9. The combined detection in the feces and blood showed a 60% MUC2 methylation rate in PC (n = 10), which was higher than those in the CP (n = 5, 0%, P < 0.01) and CON (n = 12, 0%, P < 0.01). CONCLUSIONS The study can clearly indicate that combined detection of MUC2 gene methylation in the peripheral blood and feces could be used as a new screening and early diagnosis method for pancreatic cancer.
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Affiliation(s)
- Hanyu Zhou
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Yingwei Zhu
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Feifei Wei
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Yueting Shao
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Jinjin Pan
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Ge Wang
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China
| | - Kequn Xu
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China.
| | - Yuqing Cheng
- Department of Oncology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213003, China.
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Alves Martins BA, de Bulhões GF, Cavalcanti IN, Martins MM, de Oliveira PG, Martins AMA. Biomarkers in Colorectal Cancer: The Role of Translational Proteomics Research. Front Oncol 2019; 9:1284. [PMID: 31828035 PMCID: PMC6890575 DOI: 10.3389/fonc.2019.01284] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 11/05/2019] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer is one of the most common cancers in the world, and it is one of the leading causes of cancer-related death. Despite recent progress in the development of screening programs and in the management of patients with colorectal cancer, there are still many gaps to fill, ranging from the prevention and early diagnosis to the determination of prognosis factors and treatment of metastatic disease, to establish a personalized approach. The genetic profile approach has been increasingly used in the decision-making process, especially in the choice of targeted therapies and in the prediction of drug response, but there are still few validated biomarkers of colorectal cancer for clinical practice. The discovery of non-invasive, sensitive, and specific biomarkers is an urgent need, and translational proteomics play a key role in this process, as they enable better comprehension of colorectal carcinogenesis, identification of potential markers, and subsequent validation. This review provides an overview of recent advances in the search for colorectal cancer biomarkers through proteomics studies according to biomarker function and clinical application.
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Affiliation(s)
| | - Gabriel Fonseca de Bulhões
- UniCeub—Centro Universitário Do Distrito Federal, Translational Medicine Group, School of Medicine, Brasilia, Brazil
| | - Igor Norat Cavalcanti
- UniCeub—Centro Universitário Do Distrito Federal, Translational Medicine Group, School of Medicine, Brasilia, Brazil
| | | | | | - Aline Maria Araújo Martins
- Medical Sciences Postgraduate Program, School of Medicine, University of Brasilia, Brasília, Brazil
- UniCeub—Centro Universitário Do Distrito Federal, Translational Medicine Group, School of Medicine, Brasilia, Brazil
- Metabolomics and Bioanalysis Center, San Pablo CEU University, Madrid, Spain
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Vafaei S, Fattahi F, Ebrahimi M, Janani L, Shariftabrizi A, Madjd Z. Common molecular markers between circulating tumor cells and blood exosomes in colorectal cancer: a systematic and analytical review. Cancer Manag Res 2019; 11:8669-8698. [PMID: 31576171 PMCID: PMC6768129 DOI: 10.2147/cmar.s219699] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 08/15/2019] [Indexed: 12/12/2022] Open
Abstract
Nearly half of patients with colorectal cancer (CRC), the third leading cause of cancer deaths worldwide, are diagnosed in the late stages of the disease. Appropriate treatment is not applied in a timely manner and nearly 90% of the patients who experience metastasis ultimately die. Timely detection of CRC can increase the five-year survival rate of patients. Existing histopathological and molecular classifications are insufficient for prediction of metastasis, which limits approaches to treatment. Detection of reliable cancer-related biomarkers can improve early diagnosis, prognosis, and treatment response prediction and recurrence risk. Circulating tumor cells (CTCs) and exosomes in peripheral blood can be used in a liquid biopsy to assess the status of a tumor. Exosomes are abundant and available in all fluids of the body, have a high half-life and are released by most cells. Tumor-derived exosomes are released from primary tumors or CTCs with selective cargo that represents the overall tumor. The current systematic review highlights new trends and approaches in the detection of CRC biomarkers to determine tumor signatures using CTC and exosomes. When these are combined, they could be used to guide molecular pathology and can revolutionize detection tools. Relevant observational studies published until July 24, 2019 which evaluated the expression of tumor markers in CTCs and exosomes were searched in PubMed, Scopus, Embase, and ISI Web of Science databases. The extracted biomarkers were analyzed using String and EnrichR tools.
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Affiliation(s)
- Somayeh Vafaei
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.,Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.,Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Fahimeh Fattahi
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.,Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Marzieh Ebrahimi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Leila Janani
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Zahra Madjd
- Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.,Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
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Shi Q, He Y, Zhang X, Li J, Cui G, Zhang X, Wang X. Two Novel Long Noncoding RNAs - RP11-296E3.2 and LEF1-AS1can - Separately Serve as Diagnostic and Prognostic Bio-Markers of Metastasis in Colorectal Cancer. Med Sci Monit 2019; 25:7042-7051. [PMID: 31536481 PMCID: PMC6765338 DOI: 10.12659/msm.916314] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Late diagnosis and metastasis are leading causes of the high mortality of colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been reported to play a critical role in the development and progression of CRC. This study aimed to explore the clinical significance of 2 novel lncRNAs - RP11-296E3.2 and LEF1-AS1 - including their expression pattern, as well as diagnostic and prognostic values, for metastatic CRC patients. MATERIAL AND METHODS lncRNAs expression was examined in tissues (91 cases) and plasma (60 cases) from CRC patients by real-time quantitative PCR (qRT-PCR), and the correlations between its expression and clinicopathological features and diagnosis values in metastasis were analyzed. TCGA datasets were further used to analyze their utility in prediction of overall survival (OS) and disease-free survival (DFS). ATP-based tumor chemosensitivity assay (ATP-TCA) was used to evaluated tumor chemoresistance. RESULTS Compared with adjacent normal tissues, RP11-296E3.2 was significantly downregulated while LEF1-AS1 was significantly upregulated in cancer tissues (p=0.0143, p=0.0322, respectively). High levels of RP11-296E3.2 and LEF1-AS1 in tissues and plasma were correlated with tumor metastasis (p=0.0488, p=0.0252 in tissues, p=0.0331, p=0.1862 in plasma, respectively). Further analysis showed that RP11-296E3.2 sensitivity and specificity in diagnosis of CRC metastasis is better than CEA in plasma (0.690 and 0.621, and 0.621 and 0.500, respectively), and the OS of metastatic CRC patients with higher LEF1-AS1 expression levels in tissues was short (log-rank p<0.05). CONCLUSIONS Our findings suggest that RP11-296E3.2 and LEF1-AS1 could separately serve as potential novel diagnosis and prognostic markers for CRC metastasis.
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Affiliation(s)
- Qian Shi
- First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland)
| | - Ying He
- First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland)
| | - Xilin Zhang
- First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland)
| | - Jingjing Li
- Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China (mainland)
| | - Ge Cui
- First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland)
| | - Xiuping Zhang
- Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China (mainland)
| | - Xiang Wang
- First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, China (mainland)
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Abstract
Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies' assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80-90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.
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Affiliation(s)
- John M Carethers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Department of Human Genetics and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA;
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Malagón M, Ramió-Pujol S, Serrano M, Serra-Pagès M, Amoedo J, Oliver L, Bahí A, Mas-de-Xaxars T, Torrealba L, Gilabert P, Miquel-Cusachs JO, García-Nimo L, Saló J, Guardiola J, Piñol V, Cubiella J, Castells A, Aldeguer X, Garcia-Gil J. Reduction of faecal immunochemical test false-positive results using a signature based on faecal bacterial markers. Aliment Pharmacol Ther 2019; 49:1410-1420. [PMID: 31025420 DOI: 10.1111/apt.15251] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/22/2018] [Accepted: 03/04/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Colorectal cancer is the second commonest cause of cancer mortality. Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non-invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false-positive rate. AIM To develop a new, non-invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false-positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID-CRC). METHODS We performed both the faecal immunochemical test and the bacterial markers analysis (RAID-CRC test) in stool samples from individuals with normal colonoscopy (167), non-advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer-associated symptoms. RESULTS Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut-off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population-based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false-positive rate. CONCLUSIONS RAID-CRC test allows a substantial reduction in the faecal immunochemical test false-positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer-screening scenario.
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Affiliation(s)
- Marta Malagón
- GoodGut SL, Girona, Spain.,Institut d'Investigació Biomèdica de Girona-IDIBGI, Salt, Spain.,Universitat de Girona, Girona, Spain
| | | | | | | | - Joan Amoedo
- GoodGut SL, Girona, Spain.,Universitat de Girona, Girona, Spain
| | | | - Anna Bahí
- Institut d'Investigació Biomèdica de Girona-IDIBGI, Salt, Spain
| | | | | | - Pau Gilabert
- Hospital Universitari de Bellvitge-IDIBELL, l'Hospitalet de Llobregat, Spain
| | | | - Laura García-Nimo
- Clinical Analysis Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Sanitaria Galicia Sur, Ourense, Spain
| | - Joan Saló
- Consorci Hospitalari de Vic, Vic, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge-IDIBELL, l'Hospitalet de Llobregat, Spain
| | - Virginia Piñol
- Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
| | - Joaquin Cubiella
- Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Sanitaria Galicia Sur, CIBERehd, Ourense, Spain
| | - Antoni Castells
- Gastroenterology Department, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Xavier Aldeguer
- GoodGut SL, Girona, Spain.,Institut d'Investigació Biomèdica de Girona-IDIBGI, Salt, Spain.,Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain
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Bhatt DB, Emuakhagbon VS. Current Trends in Colorectal Cancer Screening. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00432-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Liu R, Su X, Long Y, Zhou D, Zhang X, Ye Z, Ma J, Tang T, Wang F, He C. A systematic review and quantitative assessment of methylation biomarkers in fecal DNA and colorectal cancer and its precursor, colorectal adenoma. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2019; 779:45-57. [PMID: 31097151 DOI: 10.1016/j.mrrev.2019.01.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 11/15/2018] [Accepted: 01/16/2019] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) arises from accumulated genetic and epigenetic alterations, which provide the possibility to identify tumor-specific biomarkers by analyzing fecal DNA. Methylation status in human genes from tumor tissue is highlighted as promising biomarker in the early detection of CRC. A number of studies have documented altered methylation levels in DNA extracted from stool samples, but generated heterogeneous results. We performed a systematic review and quantitative assessment of existing studies to compare levels of DNA methylation in most frequently studied genes and their diagnostic value in CRC and its precursor, colorectal adenoma, with their counterparts in healthy subjects. Robust searches of the literature were performed in our study with explicit strategies and definite inclusion/exclusion criteria. Pooled data revealed that methylation levels of SFRP2, SFRP1, TFPI2, BMP3, NDRG4, SPG20, and BMP3 plus NDRG4 genes exceeded a sensitivity of 70% and a specificity of 80% for CRC detection. The DOR of the seven candidate biomarkers ranged from 19.80 to 334.33, indicating a good diagnostic power in discriminating cancer from normal tissues. The AUC range was from 0.88 to 0.95, indicating a good or very good discriminatory performance. When test results for BMP3 and NDRG4 were combined, the DOR of CRC detection was 98.36, which was higher than that for BMP3 and NDRG4 separately. As for adenoma detection, the DOR of methylated NDRG4 is higher than that for CRC (CRC vs. adenoma: 54.86 vs. 57.22). Both the sensitivity and specificity of NDRG4 for adenoma detection exceeded 70%. These findings demonstrate the eligibility and feasibility of DNA methylation as a minimally invasive biomarker in feces in the diagnosis of CRC and adenoma. The use of DNA from human stools has the potential to be readily applicable to detect aberrant DNA methylation levels among many subjects for CRC early screening.
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Affiliation(s)
- Rongbin Liu
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xuan Su
- Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China
| | - Yakang Long
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Dalei Zhou
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao Zhang
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zulu Ye
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jiangjun Ma
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Tao Tang
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Fang Wang
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
| | - Caiyun He
- Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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Chauvin A, Boisvert FM. Clinical Proteomics in Colorectal Cancer, a Promising Tool for Improving Personalised Medicine. Proteomes 2018; 6:proteomes6040049. [PMID: 30513835 PMCID: PMC6313903 DOI: 10.3390/proteomes6040049] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 11/22/2018] [Accepted: 11/29/2018] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer is the third most common and the fourth most lethal cancer worldwide. In most of cases, patients are diagnosed at an advanced or even metastatic stage, thus explaining the high mortality. The lack of proper clinical tests and the complicated procedures currently used for detecting this cancer, as well as for predicting the response to treatment and the outcome of a patient's resistance in guiding clinical practice, are key elements driving the search for biomarkers. In the present overview, the different biomarkers (diagnostic, prognostic, treatment resistance) discovered through proteomics studies in various colorectal cancer study models (blood, stool, biopsies), including the different proteomic techniques used for the discovery of these biomarkers, are reviewed, as well as the various tests used in clinical practice and those currently in clinical phase. These studies define the limits and perspectives related to proteomic biomarker research for personalised medicine in colorectal cancer.
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Affiliation(s)
- Anaïs Chauvin
- Department of Anatomy and Cell Biology, Université de Sherbrooke, 3201 Jean-Mignault, Sherbrooke, QC J1E 4K8, Canada.
| | - François-Michel Boisvert
- Department of Anatomy and Cell Biology, Université de Sherbrooke, 3201 Jean-Mignault, Sherbrooke, QC J1E 4K8, Canada.
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Nunes SP, Moreira-Barbosa C, Salta S, Palma de Sousa S, Pousa I, Oliveira J, Soares M, Rego L, Dias T, Rodrigues J, Antunes L, Henrique R, Jerónimo C. Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women. Cancers (Basel) 2018; 10:cancers10100357. [PMID: 30261643 PMCID: PMC6210550 DOI: 10.3390/cancers10100357] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 09/21/2018] [Accepted: 09/25/2018] [Indexed: 02/06/2023] Open
Abstract
Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARβ2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers’ diagnostic performance was also evaluated. Results: A “PanCancer” panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a “CancerType” panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA’s methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects’ triage, increasing compliance and cost-effectiveness.
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Affiliation(s)
- Sandra P Nunes
- Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
- Master in Oncology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
| | - Catarina Moreira-Barbosa
- Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
| | - Sofia Salta
- Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
| | - Susana Palma de Sousa
- Breast Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Inês Pousa
- Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Júlio Oliveira
- Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Marta Soares
- Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Licínio Rego
- Digestive Tract Pathology Clinic and Surgical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Teresa Dias
- Digestive Tract Pathology Clinic and Surgical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Jéssica Rodrigues
- Department of Epidemiology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Luís Antunes
- Department of Epidemiology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
| | - Rui Henrique
- Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
- Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal.
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
| | - Carmen Jerónimo
- Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
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Le Gall G, Guttula K, Kellingray L, Tett AJ, Ten Hoopen R, Kemsley EK, Savva GM, Ibrahim A, Narbad A. Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls. Oncotarget 2018; 9:33278-33289. [PMID: 30279959 PMCID: PMC6161785 DOI: 10.18632/oncotarget.26022] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 08/10/2018] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is expected to rise in the coming years. A better understanding of the metabolic changes taking place during the disease progression is needed for effective improvements of screening strategies and treatments. In the present study, Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute concentrations of metabolites in faecal extracts from two cohorts of CRC patients and healthy controls. The quantification of over 80 compounds revealed that patients with CRC had increased faecal concentrations of branched chain fatty acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but diminished concentrations of amino acids, sugars, methanol and bile acids (deoxycholate, lithodeoxycholate and cholate). These results suggest that alterations in microbial activity and composition could have triggered an increase in utilisation of host intestinal slough cells and mucins and led to an increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction in the microbial metabolic function may have led to reduced levels of other components (amino acids, sugars and bile acids) normally produced under healthy conditions. This study provides a thorough listing of the most abundant compounds found in human faecal waters and presents a template for absolute quantification of metabolites. The production of BCFA and phenylacetate in colonic carcinogenesis warrants further investigations.
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Affiliation(s)
| | - Kiran Guttula
- Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Lee Kellingray
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Adrian J Tett
- Centre for Integrative Biology, University of Trento, Trento, Italy
| | - Rogier Ten Hoopen
- Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - E Kate Kemsley
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - George M Savva
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Ashraf Ibrahim
- Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Arjan Narbad
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
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Mojtabanezhad Shariatpanahi A, Yassi M, Nouraie M, Sahebkar A, Varshoee Tabrizi F, Kerachian MA. The importance of stool DNA methylation in colorectal cancer diagnosis: A meta-analysis. PLoS One 2018; 13:e0200735. [PMID: 30024936 PMCID: PMC6053185 DOI: 10.1371/journal.pone.0200735] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 07/02/2018] [Indexed: 12/18/2022] Open
Abstract
A large number of tumor-related methylated genes have been suggested to be of diagnostic and prognostic values for CRC when analyzed in patients' stool samples; however, reported sensitivities and specificities have been inconsistent and widely varied. This meta-analysis was conducted to assess the detection accuracy of stool DNA methylation assay in CRC, early stages of CRC (advanced adenoma, non-advanced adenomas) and hyperplastic polyps, separately. We searched MEDLINE, Web of Science, Scopus and Google Scholar databases until May 1, 2016. From 469 publications obtained in the initial literature search, 38 studies were included in the final analysis involving 4867 individuals. The true positive, false positive, true negative and false negative of a stool-based DNA methylation biomarker using all single-gene tests considering a certain gene; regardless of a specific gene were pooled and studied in different categories. The sensitivity of different genes in detecting different stages of CRC ranged from 0% to 100% and the specificities ranged from 73% to 100%. Our results elucidated that SFRP1 and SFRP2 methylation possessed promising accuracy for detection of not only CRC (DOR: 31.67; 95%CI, 12.31-81.49 and DOR: 35.36; 95%CI, 18.71-66.84, respectively) but also the early stages of cancer, adenoma (DOR: 19.72; 95%CI, 6.68-58.25 and DOR: 13.20; 95%CI, 6.01-28.00, respectively). Besides, NDRG4 could be also considered as a significant diagnostic marker gene in CRC (DOR: 24.37; 95%CI, 10.11-58.73) and VIM in adenoma (DOR: 15.21; 95%CI, 2.72-85.10). In conclusion, stool DNA hypermethylation assay based on the candidate genes SFRP1, SFRP2, NDRG4 and VIM could offer potential diagnostic value for CRC based on the findings of this meta-analysis.
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Affiliation(s)
| | - Maryam Yassi
- Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran
| | - Mehdi Nouraie
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mohammad Amin Kerachian
- Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- * E-mail: ,
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Vychytilova-Faltejskova P, Stitkovcova K, Radova L, Sachlova M, Kosarova Z, Slaba K, Kala Z, Svoboda M, Kiss I, Vyzula R, Cho WC, Slaby O. Circulating PIWI-Interacting RNAs piR-5937 and piR-28876 Are Promising Diagnostic Biomarkers of Colon Cancer. Cancer Epidemiol Biomarkers Prev 2018; 27:1019-1028. [PMID: 29976566 DOI: 10.1158/1055-9965.epi-18-0318] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/01/2018] [Accepted: 06/22/2018] [Indexed: 11/16/2022] Open
Abstract
Background: The early detection of colon cancer is one of the main prerequisites for successful treatment and mortality reduction. Circulating PIWI-interacting RNAs (piRNA) were recently identified as novel promising biomarkers. The purpose of the study was to assess the profiles of piRNAs in blood serum of colon cancer patients with the aim to identify those with high diagnostic potential.Methods: Blood serum samples from 403 colon cancer patients and 276 healthy donors were included in this 3-phase biomarker study. Large-scale piRNA expression profiling was performed using Illumina small RNA sequencing. The diagnostic potential of selected piRNAs was further validated on independent training and validation sets of samples using RT-qPCR.Results: In total, 31 piRNAs were found to be significantly deregulated in serum of cancer patients compared with healthy donors. Based on the levels of piR-5937 and piR-28876, it was possible to differentiate between cancer patients and healthy donors with high sensitivity and specificity. Moreover, both piRNAs exhibited satisfactory diagnostic performance also in patients with stage I disease and enabled detection of colon cancer with higher sensitivity than currently used biomarkers CEA and CA19-9. Finally, the expression of analyzed piRNAs in blood restored significantly 1 month after the surgical resection.Conclusions: Based on our findings, piRNAs are abundant in human blood serum. Furthermore, their levels in colon cancer have been observed to be significantly deregulated. However, their involvement in carcinogenesis must be further established.Impact: piRNAs could serve as promising noninvasive biomarkers for early detection of colon cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 1019-28. ©2018 AACR.
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Affiliation(s)
- Petra Vychytilova-Faltejskova
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.,Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Karolina Stitkovcova
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Lenka Radova
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Milana Sachlova
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Zdenka Kosarova
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Katerina Slaba
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Zdenek Kala
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.,Department of Surgery, Institutions Shared with the Faculty Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Marek Svoboda
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.,Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Igor Kiss
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Rostislav Vyzula
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - William C Cho
- Cancer Research Unit, Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, PR China
| | - Ondrej Slaby
- Centre for Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic. .,Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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Lee PY, Chin SF, Low TY, Jamal R. Probing the colorectal cancer proteome for biomarkers: Current status and perspectives. J Proteomics 2018; 187:93-105. [PMID: 29953962 DOI: 10.1016/j.jprot.2018.06.014] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 06/13/2018] [Accepted: 06/23/2018] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Biomarkers that can facilitate better clinical management of CRC are in high demand to improve patient outcome and to reduce mortality. In this regard, proteomic analysis holds a promising prospect in the hunt of novel biomarkers for CRC and in understanding the mechanisms underlying tumorigenesis. This review aims to provide an overview of the current progress of proteomic research, focusing on discovery and validation of diagnostic biomarkers for CRC. We will summarize the contributions of proteomic strategies to recent discoveries of protein biomarkers for CRC and also briefly discuss the potential and challenges of different proteomic approaches in biomarker discovery and translational applications.
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Affiliation(s)
- Pey Yee Lee
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia.
| | - Siok-Fong Chin
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia
| | - Rahman Jamal
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia
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Shin HY, Suh M, Choi KS, Hwang SH, Jun JK, Han DS, Lee YK, Oh JH, Lee CW, Lee DH. Higher satisfaction with an alternative collection device for stool sampling in colorectal cancer screening with fecal immunochemical test: a cross-sectional study. BMC Cancer 2018; 18:365. [PMID: 29609647 PMCID: PMC5879644 DOI: 10.1186/s12885-018-4290-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 03/21/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Identifying preferences for stool collection devices may help increase uptake rates for colorectal cancer screening via fecal immunochemical test (FIT). This study surveyed satisfaction with different devices utilized to collect stool samples for FIT: a conventional container and a sampling bottle (Eiken OC-Sensor). METHODS This cross-sectional study was conducted at the National Cancer Center, Korea. Participants aged 50-74 years who used either a conventional container or a sampling bottle to collect a stool sample for FIT were asked to complete a questionnaire designed to survey their satisfaction with the stool collection process and their intentions to undergo FIT in subsequent screening rounds. In total, 1657 participants (1224 conventional container, 433 sampling bottle) were included for analysis. RESULTS Satisfaction with the sampling bottle was higher than that with the conventional container (79.9% vs.73.0%, p = 0.005, respectively; aOR = 1.52, 95% CI: 1.16-2.00). Participants satisfied with the sampling bottle were more likely to be female, be of younger age (50-64 years old), have higher household income, and have prior experience with FIT. Intentions to undergo subsequent screening were stronger among those given the sampling bottle than those given the conventional container (aOR = 1.78, 95% CI: 1.28-2 .48). CONCLUSIONS Satisfaction with the stool collection process was higher with the sampling bottle. However, additional studies are needed to validate whether the increased satisfaction and stronger intentions to undergo subsequent screening with the sampling bottle could actually lead to increased uptake in subsequent rounds, along with analysis of the device's cost effectiveness.
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Affiliation(s)
- Hye Young Shin
- National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
- College of Nursing, Korea University, Seoul, South Korea
| | - Mina Suh
- National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
| | - Kui Son Choi
- National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408 Republic of Korea
| | - Sang-Hyun Hwang
- Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, 05505 Republic of Korea
| | - Jae Kwan Jun
- National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408 Republic of Korea
| | - Dong Soo Han
- Department of Gastroenterology, Hanyang University Guri Hospital, 153, Gyeongchun-ro, Guri, 11923 Republic of Korea
| | - You Kyoung Lee
- Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital and Soonchunhyang University College of Medicine, 170, Jomaru-ro, Wonmi-gu, Bucheon-si, 14584 Republic of Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
| | - Chan Wha Lee
- Center for Cancer Prevention & Detection, National Cancer Center Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
| | - Do-Hoon Lee
- Department of Laboratory Medicine, Center for Diagnostic Oncology, National Cancer Center Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408 Republic of Korea
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Liao Y, Li S, Chen C, He X, Lin F, Wang J, Yang Z, Lan P. Screening for colorectal cancer in Tianhe, Guangzhou: results of combining fecal immunochemical tests and risk factors for selecting patients requiring colonoscopy. Gastroenterol Rep (Oxf) 2017; 6:132-136. [PMID: 29780602 PMCID: PMC5952940 DOI: 10.1093/gastro/gox030] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Revised: 07/16/2017] [Accepted: 07/20/2017] [Indexed: 01/16/2023] Open
Abstract
Objective To explore the performance of a protocol combining fecal immunochemical test (FIT) and a high-risk factor questionnaire (HRFQ) for selecting patients requiring colonoscopy as part of a population-based colorectal cancer (CRC) screening program in China. Methods From 2015 to 2016, we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District, Guangzhou City, China. Participants underwent an FIT and received an HRFQ as part of primary screening. Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy. Results A total of 10 074 subjects were recruited and enrolled in the screening program. In the enrolled population, 17.5% had positive FIT results and 19.4% had positive HRFQ results. Of those recommended to undergo diagnostic colonoscopy, 773 did so. The screening method’s overall positive predictive value (PPV) was 4.9% for non-adenomatous polyps, 11.4% for low-risk adenomas (LRAs), 15.9% for high-risk adenomas (HRAs) and 1.6% for CRC. The PPVs of positive FIT results for non-adenomatous polyps, LRAs, HRAs and CRC were 5.2%, 15.9%, 22.5% and 2.5%, respectively. The PPVs of positive HRFQ results for non-adenomatous polyps, LRA, HRA and CRC were 4.1%, 10.2%, 14.3% and 1.4%, respectively. The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps, LRAs, HRAs and CRC were 4.5%, 16.4%, 23.7% and 2.8%, respectively. Conclusion Our results suggest that this two-step CRC screening strategy, involving a combination of FIT and HRFQ followed by colonoscopy, is useful to identify early-stage CRC. The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.
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Affiliation(s)
- Yi Liao
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Senmao Li
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Chunyu Chen
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Xuan He
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Feng Lin
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Jianping Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease.,Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
| | - Zuli Yang
- Department of Gastrointestinal Surgery.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease
| | - Ping Lan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease.,Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, China
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Laohaviroj M, Potriquet J, Jia X, Suttiprapa S, Chamgramol Y, Pairojkul C, Sithithaworn P, Mulvenna J, Sripa B. A comparative proteomic analysis of bile for biomarkers of cholangiocarcinoma. Tumour Biol 2017; 39:1010428317705764. [PMID: 28618946 DOI: 10.1177/1010428317705764] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Cholangiocarcinoma is a primary malignant tumor of the bile duct epithelium. Cholangiocarcinoma is usually detected at an advanced stage when successful treatment is no longer possible. As the tumor originates from the bile duct epithelium, bile is an ideal source of tumor biomarkers for cholangiocarcinoma. In this study, we used a quantitative proteomics approach to identify potential tumor-associated proteins in the bile fluid of six cholangiocarcinoma patients. Three different gross-appearance tumor types were used in the analysis: mass-forming type ( n = 2), periductal infiltrating type ( n = 2), and intraductal growth type ( n = 2). Two bile samples from non-cancerous patients were used as controls. Isobaric labeling, coupled with Tandem mass spectrometry, was used to quantify protein levels in the bile of cholangiocarcinoma and control patients. In all, 63 proteins were significantly increased in cholangiocarcinoma bile compared to normal bile. Alpha-1-antitrypsin was one of the overexpressed proteins that increased in cholangiocarcinoma bile samples. Immunohistochemical analysis revealed that alpha-1-antitrypsin was detected in 177 (50%) of 354 cholangiocarcinoma tissues from our Tissue Bank. Immunoblotting of 54 cholangiocarcinoma bile samples showed that alpha-1-antitrypsin was positive in 38 (70%) samples. Fecal enzyme-linked immunosorbent assay showed that alpha-1-antitrypsin level was able to distinguish cholangiocarcinoma patients from normal individuals. In conclusion, alpha-1-antitrypsin is a potential marker for early diagnosis of cholangiocarcinoma.
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Affiliation(s)
- Marut Laohaviroj
- 1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.,2 WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center (TDRC), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Jeremy Potriquet
- 3 Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Xinying Jia
- 4 Centre for Advanced Imaging, The University of Queensland St Lucia, Brisbane, QLD, Australia
| | - Sutas Suttiprapa
- 1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.,2 WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center (TDRC), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Yaovalux Chamgramol
- 1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chawalit Pairojkul
- 1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Paiboon Sithithaworn
- 5 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Jason Mulvenna
- 3 Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
| | - Banchob Sripa
- 1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.,2 WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center (TDRC), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Banaszkiewicz Z, Budzyński J, Tojek K, Jarmocik P, Frasz J, Mrozowski M, Świtoński M, Jawień A. The fecal occult blood test as a tool for improved outpatient qualification for colonoscopy. A single-center experience and 10-year follow-up survey. Adv Med Sci 2017; 62:171-176. [PMID: 28282604 DOI: 10.1016/j.advms.2016.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 07/29/2016] [Accepted: 08/01/2016] [Indexed: 12/24/2022]
Abstract
PURPOSE Colonoscopy is not widely and easily available in all countries, even for symptomatic patients. This is one of the causes of tumors not being diagnosed until an advanced stage. The aim of this study was to estimate the efficacy of the fecal occult blood test (FOBT) in the diagnostic work-up of outpatients referred to a colorectal unit due to indistinct abdominal symptoms. PATIENTS/METHODS Among 10418 consecutive symptomatic individuals referred to the outpatient clinic, an immunochemical FOBT (Hem-Check 1®) was recommended for 9432 patients with indistinct symptoms as a tool for qualifying them for colonoscopy. All the subjects were treated according to their diagnosis and followed-up for the next 10 years. RESULTS Colorectal cancer (CRC) was diagnosed in 535 individuals: 393/986 (39.9%) among patients with red-flag symptoms, and 142/951 (14.9%) of individuals with indistinct symptoms and a positive FOBT. In the latter group, less-advanced tumors, classed as such using Dukes' classification, were twice as common and more advanced CRC occurred twice as seldom than in the former. Cancer recurrence-free and overall survival periods after surgical treatment for CRC were significantly longer in patients with indistinct symptoms who qualified for diagnostic procedures on the basis of a positive FOBT. CONCLUSIONS Patients with symptoms suggesting organic colon disease had a worse prognosis compared to individuals with non-specific symptoms. If bowel endoscopy is not widely and easily available, qualification for colonoscopy on the basis of alarm symptoms and a positive FOBT seems to be an effective strategy in early CRC diagnosis.
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Affiliation(s)
- Zbigniew Banaszkiewicz
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Chair of Vascular Surgery and Angiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland; Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Jacek Budzyński
- Chair of Vascular and Internal Diseases, Faculty of Health Sciences, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.
| | - Krzysztof Tojek
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Paweł Jarmocik
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Jacek Frasz
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Marcin Mrozowski
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Maciej Świtoński
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Jan Biziel University Hospital No. 2 in Bydgoszcz, Poland
| | - Arkadiusz Jawień
- Department of General, Gastrointestinal, Colorectal and Oncological Surgery, Chair of Vascular Surgery and Angiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland; Chair of Vascular Surgery and Angiology, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland
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Dore MP, Davoli A, Longo N, Marras G, Pes GM. Glucose-6-phosphate dehydrogenase deficiency and risk of colorectal cancer in Northern Sardinia: A retrospective observational study. Medicine (Baltimore) 2016; 95:e5254. [PMID: 27858887 PMCID: PMC5591135 DOI: 10.1097/md.0000000000005254] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with a lower cancer risk, possibly via a reduction of mutagenic oxygen-free radicals and by reducing nicotinamide-adeninedinucleotide-phosphate for replicating cells. In Sardinia, the enzyme defect is frequent as a consequence of selection by malaria in the past. This study investigated the relationship between G6PD deficiency and colorectal cancer (CRC).A retrospective case-control study of 3901 patients from Sardinia, who underwent a colonoscopy between 2006 and 2016, was performed. G6PD phenotype was assessed for each subject. The proportion of pre and malignant colorectal lesions was compared in cases (G6PD-deficient) and controls (G6PD-normal). Data concerning age, sex, family history of CRC, smoking habits, body height, and weight, and also associated diseases were collected.The CRC risk reduction was 43.2% among G6PD-deficient compared with G6PD-normal subjects (odds ratio 0.57, 95% confidence interval 0.37-0.87, P = 0.010). Age, sex, family history of CRC, and also comorbidities such as type 1 diabetes and ischemic heart disease, were significantly associated with CRC risk. The protective effect of G6PD deficiency remained significant after adjusting for all covariates by logistic regression analysis, and was consistently lower across all age groups.Glucose-6-phosphate dehydrogenase enzyme deficiency is associated with a reduced risk of CRC.
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Affiliation(s)
- Maria P. Dore
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Italy
- Baylor College of Medicine, Houston, TX, USA
- Correspondence: Maria Pina Dore, Clinica Medica, Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, 07100 Sassari, Italy (e-mail: )
| | - Agnese Davoli
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Italy
| | - Nunzio Longo
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Italy
| | - Giuseppina Marras
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Italy
| | - Giovanni M. Pes
- Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Italy
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Wang R, Du L, Yang X, Jiang X, Duan W, Yan S, Xie Y, Zhu Y, Wang Q, Wang L, Yang Y, Wang C. Identification of long noncoding RNAs as potential novel diagnosis and prognosis biomarkers in colorectal cancer. J Cancer Res Clin Oncol 2016; 142:2291-301. [PMID: 27591862 DOI: 10.1007/s00432-016-2238-9] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 08/30/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is prevalent worldwide, and improvements in timely and effective diagnosis are imperatively needed. We aimed to identify potential long noncoding RNA (lncRNA) biomarkers for CRC diagnosis along with prognosis prediction. METHODS LncRNA expression profiles were studied by microarray in paired tumor and normal tissues from six patients with CRC. The expression levels of candidate lncRNAs were analyzed in 80 pairs of tissues and two independent cohorts of serum samples. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the lncRNAs identified. The correlation between lncRNAs and disease-specific survival rate of CRC patients was assessed to explore prognostic potential. RESULTS Four lncRNAs (BANCR, NR_026817, NR_029373, and NR_034119) were identified to be significantly dysregulated in both tissue and serum samples with consistent pattern, and a panel was established based on this result. The performance of the 4-lncRNA panel was measured with an area under the ROC curve (AUC) of 0.881. The corresponding AUCs of the panel for patients with TNM stageI, II and III were 0.774, 0.844 and 0.949, respectively, significantly higher than that of CEA. Kaplan-Meier analysis showed that patients with low levels of NR_029373 and NR_034119 had significantly lower disease-specific survival rate (p = 0.013 and 0.044, respectively). Multivariate Cox analysis demonstrated that NR_029373 and NR_034119 were both independently associated with disease-specific survival rate (p = 0.013 and 0.038, respectively). CONCLUSIONS Our study established a distinctive 4-lncRNA panel with considerable diagnostic value and identified NR_029373 and NR_034119 as potential biomarkers for CRC prognosis prediction.
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Affiliation(s)
- Rui Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Lutao Du
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Xiaoyun Yang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Xiumei Jiang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Weili Duan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Suzhen Yan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Yujiao Xie
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Yuntao Zhu
- Department of Clinical Laboratory, Jinxiang County People's Hospital, Jining, 272000, Shandong Province, China
| | - Qingliang Wang
- Department of Medical Affairs Management, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Lili Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Yongmei Yang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China
| | - Chuanxin Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong Province, China.
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