Novel Approaches in the Diagnosis of Primary and Secondary Disease within Colorectal Cancer

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 29606

Special Issue Editors

Medicine Faculty, Uiversidad Complutense, Madrid, Spain
Interests: molecular genetics; omics technologies; prognostic and diagnostic biomarkers; cancer research; genetic epidemiology; statistics
Fundación Jiménez Díaz, University Hospital, Madrid, Spain
Interests: colorectal cancer (early-onset CRC, multiple primary CRC, hereditary forms); other digestive tract malignancies

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most common cancer with 1.8 million new cases diagnosed  and 81,000  deaths associated with the disease in 2018. In this special issue, we update the new approaches for the screening and diagnosis of CRC including primary and  metastatic disease , as well as recurrent disease.

Main topics are liquid biopsy, microbiome, and other non-invasive strategies. The latest advances in routine management for diagnosis, endoscopic and/or radiological findings are welcome. Diagnostic tactics for hereditary CRC forms or IBD-associated CRC are also invited.

Prof. Lucía Inglada-Pérez
Dr. José Perea
Guest Editors

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Keywords

  • colorectal cancer
  • primary tumor
  • recurrence
  • metastatic disease
  • microbiome
  • liquid biopsy

Published Papers (12 papers)

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Research

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13 pages, 843 KiB  
Article
The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics
by Hsien-Cheng Huang, Bei-Hao Shiu, Shih-Chi Su, Chi-Chou Huang, Wen-Chien Ting, Lun-Ching Chang, Shun-Fa Yang and Ying-Erh Chou
Diagnostics 2022, 12(7), 1685; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12071685 - 11 Jul 2022
Cited by 4 | Viewed by 1414
Abstract
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In [...] Read more.
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In this study, we focused on the associations of MMP-11 single-nucleotide polymorphisms (SNPs) with CRC susceptibility and clinicopathological characteristics. The MMP-11 SNPs rs131451, rs738791, rs2267029, rs738792, and rs28382575 in 479 controls and 479 patients with CRC were analyzed with real-time polymerase chain reaction. We found that the MMP-11 SNP rs738792 “TC + CC” genotype was significantly associated with perineural invasion in colon cancer patients after controlling for clinical parameters [OR (95% CI) = 1.783 (1.074–2.960); p = 0.025]. The MMP-11 rs131451 “TC + CC” genotypic variants were correlated with greater tumor T status [OR (95% CI):1.254 (1.025–1.534); p = 0.028] and perineural invasion [OR (95% CI):1.773 (1.027–3.062); p = 0.040) in male CRC patients. Furthermore, analyses of The Cancer Genome Atlas (TCGA) revealed that MMP-11 levels were upregulated in colorectal carcinoma tissue compared with normal tissues and were correlated with advanced stage, larger tumor sizes, and lymph node metastasis. Moreover, the data from the Genotype-Tissue Expression (GTEx) database exhibited that the MMP-11 rs738792 “CC” and “CT” genotypic variants have higher MMP-11 expression than the “TT” genotype. In conclusion, our results have demonstrated that the MMP-11 SNPs rs738792 and rs131451 may have potential to provide biomarkers to evaluate CRC disease progression, and the MMP-11 rs131451 polymorphism may shed light on sex discrepancy in CRC development and prognosis. Full article
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12 pages, 814 KiB  
Article
Primary Tumor Resection Provides Survival Benefits for Patients with Synchronous Brain Metastases from Colorectal Cancer
by Xiaofei Cheng, Yanqing Li, Dong Chen, Xiangming Xu, Fanlong Liu and Feng Zhao
Diagnostics 2022, 12(7), 1586; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12071586 - 29 Jun 2022
Cited by 3 | Viewed by 1386
Abstract
Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefits to patients with BMs of CRC [...] Read more.
Background: Brain metastases (BMs), particularly synchronous brain metastases, in colorectal cancer (CRC) patients are uncommon. The survival benefit of primary tumor resection (PTR) in patients with metastatic colorectal cancer is controversial. Whether PTR can bring survival benefits to patients with BMs of CRC has not been reported. Methods: From 2010 to 2016, 581 CRC patients with BMs from the Surveillance, Epidemiology, and End Results (SEER) database were divided into PTR and non-PTR groups. The log-rank test was used to compare the survival distributions. The Kaplan-Meier method was used to estimate survival. By controlling additional prognostic factors, a Cox proportional multivariate regression analysis was used to estimate the survival benefit of PTR. Results: The median overall survival for CRC patients with synchronous BMs was 3 months, with a 1-year survival rate of 27.2% and a 2-year survival rate of 12.8%. The PTR group contained 171 patients (29.4%), whereas the non-PTR group had 410 patients (70.6%). Patients who underwent PTR had a 1-year survival rate of 40.2% compared to 21.7% in those who did not (p < 0.0001). Cox proportional analysis showed that patients ≥60 years (hazard ratio [HR] 1.718, 95% confidence interval [CI] 1.423–2.075, p < 0.0001) had a shorter OS than patients < 60 years of age. OS was better in CEA-negative than in CEA-positive patients (HR 0.652, 95% CI 0.472–0.899, p = 0.009). Patients in whom the primary tumor was removed had considerably improved prognoses (HR 0.654, 95% CI 0.531–0.805, p < 0.0001). Subgroup analysis revealed that the PTR group achieved a survival advantage except for patients with CEA negative. Conclusions: Patients with synchronous BMs from CRC may benefit from primary tumor resection (PTR). Age, CEA level, and PTR were independent prognostic risk factors for CRC patients with synchronous BMs. Full article
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11 pages, 1596 KiB  
Article
Nomogram Predicting the Survival of Young-Onset Patients with Colorectal Cancer Liver Metastases
by Xiaofei Cheng, Yanqing Li, Dong Chen, Xiangming Xu, Fanlong Liu and Feng Zhao
Diagnostics 2022, 12(6), 1395; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics12061395 - 04 Jun 2022
Cited by 6 | Viewed by 1966
Abstract
Background: Although the global prevalence of colorectal cancer (CRC) is decreasing, there has been an increase in incidence among young-onset individuals, in whom the disease is associated with specific pathological characteristics, liver metastases, and a poor prognosis. Methods: From 2010 to 2016, 1874 [...] Read more.
Background: Although the global prevalence of colorectal cancer (CRC) is decreasing, there has been an increase in incidence among young-onset individuals, in whom the disease is associated with specific pathological characteristics, liver metastases, and a poor prognosis. Methods: From 2010 to 2016, 1874 young-onset patients with colorectal cancer liver metastases (CRLM) from the Surveillance, Epidemiology, and End Results (SEER) database were randomly allocated to training and validation cohorts. Multivariate Cox analysis was used to identify independent prognostic variables, and a nomogram was created to predict cancer-specific survival (CSS) and overall survival (OS). Receiver operating characteristic (ROC) curve, C-index, area under the curve (AUC), and calibration curve analyses were used to determine nomogram accuracy and reliability. Results: Factors independently associated with young-onset CRLM CSS included primary tumor location, the degree of differentiation, histology, M stage, N stage, preoperative carcinoembryonic antigen level, and surgery (all p < 0.05). The C-indices of the CSS nomogram for the training and validation sets (compared to TNM stage) were 0.709 and 0.635, and 0.735 and 0.663, respectively. The AUC values for 1-, 3-, and 5-year OS were 0.707, 0.708, and 0.755 in the training cohort and 0.765, 0.735, and 0.737 in the validation cohort, respectively; therefore, the nomogram had high sensitivity, and was superior to TNM staging. The calibration curves for the training and validation sets were relatively consistent. In addition, a similar result was observed with OS. Conclusions: We developed a unique nomogram incorporating clinical and pathological characteristics to predict the survival of young-onset patients with CRLM. This may serve as an early warning system allowing doctors to devise more effective treatment regimens. Full article
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20 pages, 4537 KiB  
Article
Ex Vivo Vibration Spectroscopic Analysis of Colorectal Polyps for the Early Diagnosis of Colorectal Carcinoma
by Alla Synytsya, Aneta Vaňková, Michaela Miškovičová, Jaromír Petrtýl and Luboš Petruželka
Diagnostics 2021, 11(11), 2048; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112048 - 04 Nov 2021
Cited by 5 | Viewed by 1529
Abstract
Colorectal cancer is one of the most common and often fatal cancers in humans, but it has the highest chance of a cure if detected at an early precancerous stage. Carcinogenesis in the colon begins as an uncontrolled growth forming polyps. Some of [...] Read more.
Colorectal cancer is one of the most common and often fatal cancers in humans, but it has the highest chance of a cure if detected at an early precancerous stage. Carcinogenesis in the colon begins as an uncontrolled growth forming polyps. Some of these polyps can finally be converted to colon cancer. Early diagnosis of adenomatous polyps is the main approach for screening and preventing colorectal cancer, and vibration spectroscopy can be used for this purpose. This work is focused on evaluating FTIR and Raman spectroscopy as a tool in the ex vivo analysis of colorectal polyps, which could be important for the early diagnosis of colorectal carcinoma. Multivariate analyses (PCA and LDA) were used to assist the spectroscopic discrimination of normal colon tissue, as well as benign and malignant colon polyps. The spectra demonstrated evident differences in the characteristic bands of the main tissue constituents, i.e., proteins, nucleic acids, lipids, polysaccharides, etc. Suitable models for discriminating the three mentioned diagnostic groups were proposed based on multivariate analyses of the spectroscopic data. LDA classification was especially successful in the case of a combined set of 55 variables from the FTIR, FT Raman and dispersion Raman spectra. This model can be proposed for ex vivo colorectal cancer diagnostics in combination with the colonoscopic extraction of colon polyps for further testing. This pilot study is a precursor for the further evaluation of the diagnostic potential for the simultaneous in vivo application of colonoscopic Raman probes. Full article
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11 pages, 3203 KiB  
Article
Comparative Analysis of Circulating Biomarkers for Patients Undergoing Resection of Colorectal Liver Metastases
by Sven H. Loosen, Christoph Roderburg, Patrick H. Alizai, Anjali A. Roeth, Sophia M. Schmitz, Mihael Vucur, Mark Luedde, David Schöler, Pia Paffenholz, Frank Tacke, Christian Trautwein, Tom Luedde, Ulf P. Neumann and Tom F. Ulmer
Diagnostics 2021, 11(11), 1999; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11111999 - 27 Oct 2021
Cited by 4 | Viewed by 1831
Abstract
Surgical tumor resection has evolved as a potentially curative therapy for patients with resectable colorectal liver metastases (CRLM). However, disease recurrence is common and the available preoperative stratification strategies are often imprecise to identify the ideal candidates for surgical treatment, resulting in a [...] Read more.
Surgical tumor resection has evolved as a potentially curative therapy for patients with resectable colorectal liver metastases (CRLM). However, disease recurrence is common and the available preoperative stratification strategies are often imprecise to identify the ideal candidates for surgical treatment, resulting in a postoperative 5-year survival rate below 50%. Data on the prognostic value of CEA, CA19-9 and other common laboratory parameters after CRLM resection are scarce and partly inconclusive. Here, we analyzed the prognostic potential of circulating CEA and CA19-9 in comparison to other standard laboratory markers in resectable CRLM patients. Serum levels of tumor markers and other laboratory parameters were analyzed in 125 patients with CRLM undergoing tumor resection at a tertiary referral center. Results were correlated with clinical data and outcome. Both tumor markers were significantly elevated in CRLM patients compared to healthy controls. Interestingly, elevated levels of CEA, CA19-9 and C-reactive protein (CRP) were associated with an unfavorable prognosis after CRLM resection in Kaplan–Meier curve analysis. However, only CEA and not CA19-9 or CRP serum levels were an independent prognostic marker in multivariate Cox regression analysis. Our data demonstrate that circulating levels of CEA rather than CA19-9 might be a valuable addition to the existing preoperative stratification algorithms to identify patients with a poor prognosis after CRLM resection. Full article
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16 pages, 1228 KiB  
Article
The Relationship between Inflammation Markers (CRP, IL-6, sCD40L) and Colorectal Cancer Stage, Grade, Size and Location
by Olga Martyna Koper-Lenkiewicz, Violetta Dymicka-Piekarska, Anna Justyna Milewska, Justyna Zińczuk and Joanna Kamińska
Diagnostics 2021, 11(8), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11081382 - 31 Jul 2021
Cited by 7 | Viewed by 1995
Abstract
The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean [...] Read more.
The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed. Full article
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10 pages, 1012 KiB  
Article
Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer
by Bei-Hao Shiu, Ming-Hong Hsieh, Wen-Chien Ting, Ming-Chih Chou, Lun-Ching Chang, Chi-Chou Huang, Shih-Chi Su and Shun-Fa Yang
Diagnostics 2021, 11(6), 978; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11060978 - 28 May 2021
Cited by 6 | Viewed by 2342
Abstract
Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development [...] Read more.
Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; p = 0.046) or rs351855 (GA and AA; AOR, 0.191; p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression. Full article
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11 pages, 632 KiB  
Article
Blood-Based Detection of Colorectal Cancer Using Cancer-Specific DNA Methylation Markers
by Nam-Yun Cho, Ji-Won Park, Xianyu Wen, Yun-Joo Shin, Jun-Kyu Kang, Sang-Hyun Song, Hwang-Phill Kim, Tae-You Kim, Jeong Mo Bae and Gyeong Hoon Kang
Diagnostics 2021, 11(1), 51; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11010051 - 31 Dec 2020
Cited by 12 | Viewed by 3215
Abstract
Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA [...] Read more.
Cancer tissues have characteristic DNA methylation profiles compared with their corresponding normal tissues that can be utilized for cancer diagnosis with liquid biopsy. Using a genome-scale DNA methylation approach, we sought to identify a panel of DNA methylation markers specific for cell-free DNA (cfDNA) from patients with colorectal cancer (CRC). By comparing DNA methylomes between CRC and normal mucosal tissues or blood leukocytes, we identified eight cancer-specific methylated loci (ADGRB1, ANKRD13, FAM123A, GLI3, PCDHG, PPP1R16B, SLIT3, and TMEM90B) and developed a five-marker panel (FAM123A, GLI3, PPP1R16B, SLIT3, and TMEM90B) that detected CRC in liquid biopsies with a high sensitivity and specificity with a droplet digital MethyLight assay. In a set of cfDNA samples from CRC patients (n = 117) and healthy volunteers (n = 60), a panel of five markers on the platform of the droplet digital MethyLight assay detected stages I–III and stage IV CRCs with sensitivities of 45.9% and 95.7%, respectively, and a specificity of 95.0%. The number of detected markers was correlated with the cancer stage, perineural invasion, lymphatic emboli, and venous invasion. Our five-marker panel with the droplet digital MethyLight assay showed a high sensitivity and specificity for the detection of CRC with cfDNA samples from patients with metastatic CRC. Full article
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13 pages, 871 KiB  
Article
Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort
by Noel Pin-Vieito, María José Iglesias, David Remedios, Victoria Álvarez-Sánchez, Fernando Fernández-Bañares, Jaume Boadas, Eva Martínez-Bauer, Rafael Campo, Luis Bujanda, Ángel Ferrández, Virginia Piñol, Daniel Rodríguez-Alcalde, Martín Menéndez-Rodríguez, Natalia García-Morales, Cristina Pérez-Mosquera and Joaquín Cubiella
Diagnostics 2020, 10(12), 1036; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10121036 - 02 Dec 2020
Cited by 1 | Viewed by 1939
Abstract
We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within [...] Read more.
We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3–3.1), CRC (HR 4.4, 95% CI 1.1–17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0–2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3–5.8), rectal bleeding (OR 0.3, 95% CI 0.1–0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7–7.1). However, CEA was increased only in 31.8% (95% CI, 16.4–52.7%) and 50% (95% CI, 25.4–74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC. Full article
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13 pages, 666 KiB  
Article
Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer
by Olalla Otero-Estévez, María Gallardo-Gomez, María Páez de la Cadena, Francisco Javier Rodríguez-Berrocal, Joaquín Cubiella, Vicent Hernandez Ramirez, Laura García-Nimo and Loretta De Chiara
Diagnostics 2020, 10(7), 437; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10070437 - 28 Jun 2020
Cited by 8 | Viewed by 2368
Abstract
Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter [...] Read more.
Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia—AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35–47% AA (specificity 98–95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals. Full article
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Review

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20 pages, 1270 KiB  
Review
Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells
by Francis Yew Fu Tieng, Nadiah Abu, Siti Nurmi Nasir, Learn-Han Lee and Nurul-Syakima Ab Mutalib
Diagnostics 2021, 11(11), 2136; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11112136 - 17 Nov 2021
Cited by 5 | Viewed by 2471
Abstract
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection [...] Read more.
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods. Full article
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21 pages, 1103 KiB  
Review
Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC)
by Siew-Wai Pang, Noel Jacques Awi, Subasri Armon, Wendy Wan-Dee Lim, John Seng-Hooi Low, Kaik-Boo Peh, Suat-Cheng Peh and Sin-Yeang Teow
Diagnostics 2020, 10(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10010009 - 23 Dec 2019
Cited by 19 | Viewed by 5768
Abstract
Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen [...] Read more.
Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen significant improvement since the advent of target-specific therapies and personalized medicine, CRC is oftentimes detected at late or advanced stages, thereby reducing the efficacy of treatment. Hence, screening for early detection is still the key to combat CRC and to increase overall survival (OS). Considering that the field of medical diagnostics is moving towards molecular diagnostics, CRC can now be effectively screened and diagnosed with high accuracy and sensitivity. Depending on the tumor genotype and genetic profile of the individual, personalized treatments including tyrosine kinase inhibitor therapy and immunotherapy can be administered. Notably, there can be no one single treatment that is effective for all CRC patients due to the variation in tumor genetics, which highlights the importance of molecular diagnostics. This review provides insights on therapeutic modalities, molecular biomarkers, advancement of diagnostic technologies, and current challenges in managing CRC. Full article
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