scholarly journals Promising Colorectal Cancer Biomarkers for Precision Prevention and Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1932 ◽  
Author(s):  
Mimmo Turano ◽  
Paolo Delrio ◽  
Daniela Rega ◽  
Francesca Cammarota ◽  
Alessia Polverino ◽  
...  

Colorectal cancer (CRC) has been ranked as the third most prevalent cancer worldwide. Indeed, it represents 10.2% of all cancer cases. It is also the second most common cause of cancer mortality, and accounted for about 9.2% of all cancer deaths in 2018. Early detection together with a correct diagnosis and staging remains the most effective clinical strategy in terms of disease recovery. Thanks to advances in diagnostic techniques, and improvements of surgical adjuvant and palliative therapies, the mortality rate of CRC has decreased by more than 20% in the last decade. Cancer biomarkers for the early detection of CRC, its management, treatment and follow-up have contributed to the decrease in CRC mortality. Herein, we provide an overview of molecular biomarkers from tumor tissues and liquid biopsies that are approved for use in the CRC clinical setting for early detection, follow-up, and precision therapy, and of biomarkers that have not yet been officially validated and are, nowadays, under investigation.

2021 ◽  
pp. 1-30
Author(s):  
Maryam Alizadeh-Sedigh ◽  
Mohammad Sadegh Fazeli ◽  
Habibollah Mahmoodzadeh ◽  
Shahin Behrouz Sharif ◽  
Ladan Teimoori-Toolabi

BACKGROUND: Investigating aberrant tumor-specific methylation in plasma cell-free DNA provides a promising and noninvasive biomarker for cancer detection. OBJECTIVE: We aimed to investigate methylation status of some promoter regions in the plasma and tumor tissues to find biomarkers for early detection of colorectal cancer. METHODS: This case-control study on seventy colorectal cancer patients and fifty matched healthy controls used Methylation-Specific High-Resolution Melting Curve analysis to evaluate the methylation of the selected promoter regions in converted genomic tissue DNA and plasma cfDNA. RESULTS: The methylation levels in selected regions of SPG20 (+24375 to +24680, +24209 to +24399, and +23625 to +23883), SNCA (+807 to +1013, +7 to +162, and -180 to +7), FBN1 (+223 to +429, +1 to +245, and -18 to -175), ITF2 (+296 to +436 and -180 to +55), SEPT9 (-914412 to -91590 and -99083 to -92264), and MLH1 (-13 to +22) were significantly higher in tumor tissues compared with normal adjacent tissues. The methylation levels of FBN1, ITF2, SNCA, and SPG20 promoters were significantly higher in the patient’s plasma compared to patient’s normal tissue and plasma of healthy control subjects. FBN1, SPG20, and SEPT9 promoter methylation had a good diagnostic performance for discriminating CRC tissues from normal adjacent tissues (AUC > 0.8). A panel of SPG20, FBN1, and SEPT9 methylation had a higher diagnostic value than that of any single biomarker and other panels in tissue-based assay (AUC > 0.9). The methylation of FBN1(a) and SPG20(a) regions, as the closest region to the first coding sequence (CDS), had a good diagnostic performance in plasma cfDNA (AUC > 0.8) while a panel consisted of FBN1(a) and SPG20(a) regions showed excellent diagnostic performance for CRC detection in plasma cfDNA (AUC > 0.9). CONCLUSION: Methylation of FBN1(a) and SPG20(a) promoter regions in the plasma cfDNA can be an excellent simple, non-invasive blood-based test for early detection of CRC.


2019 ◽  
Vol 6 (7) ◽  
pp. 3315-3324 ◽  
Author(s):  
Masoud Negahdary ◽  
Ali Moradi ◽  
Hossein Heli

Today, the late diagnosis of cancers is a big challenge, and using novel diagnostic techniques will provide essential, faster and more accurate treatments. Unfortunately, existing common and traditional diagnostic methods have not been helpful completely and most cancers are diagnosed too late. Recently, researchers have found new diagnostic methods against cancers by aptasensors; these sensory systems can detect involved biomarkers in various cancers so that the research in this field is continued strictly. Aptasensors can detect cancer markers in small quantities and high selectivity; moreover, other advantages of cancer aptasensors such as optimized time and cost saving can be considered. In addition, the aptasensors have been used in the diagnosis of the effective and related factors in cancer therapy follow-up. Here, the most researches about cancer aptasensors and other involved markers were collected, reviewed and described.  


2008 ◽  
Vol 98 (5) ◽  
pp. 875-880 ◽  
Author(s):  
I Sobhani ◽  
E Tiret ◽  
R Lebtahi ◽  
T Aparicio ◽  
E Itti ◽  
...  

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 510-510
Author(s):  
John Chang ◽  
Russell Pluhm ◽  
Ashley Lutrick ◽  
Jessica Guerra ◽  
Phillip Koo ◽  
...  

510 Background: We have previously reported that up to 48% of the early features of colorectal cancer (subtle wall thickening, pericolonic stranding, and small lymph nodes in the draining nodal station) were not identified on the original CT abdomen and pelvis (CTAP) reports. This resulted in a 36% decrease in five-year survival based on historical data. In this report, we assessed whether dedicated assessment of the colon on routine CT scans could lead to early detection of colorectal cancer. Methods: 210 CTAPs over a three-month period were screened from the emergency room records at a tertiary care hospital. 194 scans met eligibility. Exclusion criteria included: cases known to the evaluating radiologist and age ≤ 19 or > 89 years. No study was excluded for suboptimal image quality. The original report was reviewed for abnormalities involving the colon, mesentery and bowel and was recorded. A blinded evaluation of the eligible case was then performed by a board-certified radiologist with attention specifically to the colon and the mesentery for the suspicious early features of CRC. The concordance and discordance was then tabulated. Discordant findings were re-evaluated to determine if the discordance was true. Results: 72/194 patients were male, median age 44.5 years (range 20 - 89). 55/194 patients (29.1%) included in the study were noted to have suspicious features. 26 had abnormal lymph nodes, 24 had abnormal colonic wall thickening and 16 had pericolonic stranding and/or wall edema. 45/55 studies were truly discordant from the original interpretation. These included one missed colorectal cancer (confirmed), one likely small bowel neuroendocrine tumor (no follow up), and one likely transitional cell carcinoma of the right renal pelvis (no follow up). Conclusions: Dedicated search of the colon and mesentery on CTAP can identify subtle findings, although their true relevance is being evaluated in a larger future study. Our observational data does indicate that there maybe a potential role for a focused evaluation of the colon and mesentery on routine CTAP in an attempt to potentially increase the rate of cancer detection especially in younger low-average risk patients.


Author(s):  
Eivor Alette Laugsand ◽  
Siv Sellæg Brenne ◽  
Frank Skorpen

Abstract Purpose Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC. Methods The databases MEDLINE, Web of Science, and Embase were systematically searched. Data extraction and review was performed by two authors independently. Agreement between methylation status in tissue and other materials (blood/stool/urine) was analyzed using the McNemar test and Cohen’s kappa. Results From the 51 included studies, we identified seven single markers with sensitivity ≥ 75% and specificity ≥ 90% for CRC. We also identified one promising plasma panel and two stool panels. The correspondence of methylation status was evaluated as very good for four markers, but only marginal for most of the other markers investigated (12 of 21). Conclusion The included studies reported only some of the variables and markers of interest and included few patients. Hence, a meta-analysis was not possible at this point. Larger, prospective studies must be designed to study the discordant detection of markers in tissue and liquid biopsies. When reporting their findings, such studies should use a standardized format.


Author(s):  
Aitor Rodriguez-Casanova ◽  
Nicolás Costa-Fraga ◽  
Aida Bao-Caamano ◽  
Rafael López-López ◽  
Laura Muinelo-Romay ◽  
...  

Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.


2020 ◽  
Vol 58 (10) ◽  
pp. 1651-1653
Author(s):  
Clare Fiala ◽  
Eleftherios P. Diamandis

AbstractThe important conclusion that ctDNA is a mediocre proxy for liquid biopsies of tumor tissues for early detection was reached after new data were published recently in Nature Genetics. These data have shown that most mutations found in ctDNA are not related to tumor tissues but rather to the precancerous condition clonal hematopoiesis. Previously, our group has analyzed the sensitivity of the ctDNA test for early detection of cancer and concluded that the achievable sensitivity, especially for small tumors, is not enough to have clinical value. Now, the new data have shown a serious compromise in specificity. We believe that scientists who are interested in early cancer diagnostics should be aware of the limitations of this test, in both sensitivity and specificity. Our work may prompt further work aiming to alleviate these important issues in the cancer diagnostics field.


Cancer ◽  
1984 ◽  
Vol 54 (5) ◽  
pp. 791-793 ◽  
Author(s):  
Hugo Bühlermd ◽  
Ulrich Seefeld ◽  
Peter Deyhle ◽  
Peter Buchmann ◽  
Urs Metzger ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4803
Author(s):  
Satoshi Nagayama ◽  
Siew-Kee Low ◽  
Kazuma Kiyotani ◽  
Yusuke Nakamura

In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.


2010 ◽  
Vol 8 (7) ◽  
pp. 543
Author(s):  
T. Nasser ◽  
F. Younis ◽  
D. Mcgrath ◽  
J. Hernon ◽  
C. Speakman ◽  
...  

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