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Biomarkers of Colorectal Cancer
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Biomarkers of Colorectal Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 32184

Special Issue Editor

Prof. Dr. Sten Hammarström

E-Mail Website
Guest Editor
Faculty of Medicine, Department of Clinical Microbiology, Umeå University, Umeå, Sweden
Interests: colorectal cancer; biomarkers; mucosal immunology; gut microbiota; celiac disease; inflammatory bowel disease; host–parasite interactions

Special Issue Information

Dear Colleagues,

Colorectal cancer is the third most common cancer form worldwide, with a global incidence of almost 2 million new cases per year (10.2% of all cancers). The curative treatment of colorectal cancer is surgery. Despite significant progress in treatment during recent years, almost 50% of patients die from the disease. Therefore, there is an urgent need to improve possibilities for early diagnosis, ability to detect regional metastases, monitor disease development, and develop new treatment modalities.

Biomarkers as proxies for tumors cells, particularly biomarkers that can differentiate between aggressive tumor cells and less aggressive tumors cells, can play a very important role in improving patients’ survival. Biomarker levels may be determined at the protein and mRNA levels in the primary tumor, in lymph node metastases, in liquid biopsies, and in feces.

In this Special Issue, we invite you to contribute an original research article or a review with a focus on biomarkers that can be used either for early diagnosis, detection of tumor spread, and/or targets for treatment. Emphasis should be on quantitative molecular methods.

Prof. Dr. Sten Hammarström
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Metastases/micrometastases
  • Lymph node status
  • Tumor spread
  • Tumor microenvironment

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Published Papers (6 papers)

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Research

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18 pages, 6561 KiB  
Article
Vitamin C—Protective Role in Oxidative Stress Conditions Induced in Human Normal Colon Cells by Label-Free Raman Spectroscopy and Imaging
by Karolina Beton and Beata Brozek-Pluska
Int. J. Mol. Sci. 2021, 22(13), 6928; https://doi.org/10.3390/ijms22136928 - 28 Jun 2021
Cited by 8 | Viewed by 2884
Abstract
Colorectal cancer is the second most frequently diagnosed cancer worldwide. Conventional diagnostics methods of colorectal cancer can detect it at an advanced stage. Spectroscopic methods, including Raman spectroscopy and imaging, are becoming more and more popular in medical applications, and allow fast, precise, [...] Read more.
Colorectal cancer is the second most frequently diagnosed cancer worldwide. Conventional diagnostics methods of colorectal cancer can detect it at an advanced stage. Spectroscopic methods, including Raman spectroscopy and imaging, are becoming more and more popular in medical applications, and allow fast, precise, and unambiguous differentiation of healthy and cancerous samples. The most important advantage of Raman spectroscopy is the ability to identify biomarkers that help in the differentiation of healthy and cancerous cells based on biochemistry of sample and spectra typical for lipids, proteins, and DNA. The aim of the study was to evaluate the biochemical and structural features of human colon cell lines based on Raman spectroscopy and imaging: normal cells CCD-18 Co, normal cells CCD-18 Co under oxidative stress conditions, and normal cells CCD-18 Co at first treated by using tert-Butyl hydroperoxide and then supplemented by vitamin C in high concentration to show the protective role of vitamin C in micromolar concentrations against ROS (Reactive Oxygen Species). Raman data obtained for normal cells injured by ROS were compared with spectra typical for cancerous cells. Statistically assisted analysis has shown that normal ROS-injured and cancerous human colon cells can be distinguished based on their unique vibrational properties. The research carried out proves that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of normal and cancerous colon cells and may be a source of intraoperative information supporting histopathological analysis. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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13 pages, 2104 KiB  
Article
High Concordance of Genomic Profiles between Primary and Metastatic Colorectal Cancer
by Seung Eun Lee, Ha Young Park, Dae-Yong Hwang and Hye Seung Han
Int. J. Mol. Sci. 2021, 22(11), 5561; https://doi.org/10.3390/ijms22115561 - 24 May 2021
Cited by 7 | Viewed by 2846
Abstract
The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including [...] Read more.
The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including 95 pairs of primary and metastatic CRCs, to reveal their genomic characteristics and to assess the genetic heterogeneity. The most frequently mutated gene in primary and metastatic CRCs was APC (71% vs. 65%), TP53 (54% vs. 57%), KRAS (45% vs. 44%), PIK3CA (16% vs. 19%), SMAD4 (15% vs. 14%) and FBXW7 (11% vs. 11%). The concordance in the top six frequently mutated genes was 85%, on average. The overall mutation frequencies were consistent with two sets of public data (TCGA and MSKCC). To the author’s knowledge, this is the first study to compare the genetic profiles of our cohort with that of the metastatic CRCs from MSKCC. Comparative sequencing analysis between primary and metastatic CRCs revealed a high degree of genetic concordance in the current clinically actionable genes. Therefore, the genetic investigation of archived primary tumor samples with the challenges of obtaining an adequate sample from metastatic sites appears to be sufficient for the application of cancer precision medicine in the metastatic setting. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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Review

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14 pages, 447 KiB  
Review
Inflammation-Related Biomarkers for the Prediction of Prognosis in Colorectal Cancer Patients
by Takehito Yamamoto, Kenji Kawada and Kazutaka Obama
Int. J. Mol. Sci. 2021, 22(15), 8002; https://doi.org/10.3390/ijms22158002 - 27 Jul 2021
Cited by 201 | Viewed by 9172
Abstract
Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and [...] Read more.
Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil–lymphocyte ratio (NLR), lymphocyte–C-reactive protein ratio (LCR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients’ prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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23 pages, 1534 KiB  
Review
Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era
by Guido Giordano, Pietro Parcesepe, Giuseppina Bruno, Annamaria Piscazzi, Vincenzo Lizzi, Andrea Remo, Massimo Pancione, Mario Rosario D’Andrea, Elena De Santis, Luigi Coppola, Michele Pietrafesa, Alberto Fersini, Antonio Ambrosi and Matteo Landriscina
Int. J. Mol. Sci. 2021, 22(14), 7717; https://doi.org/10.3390/ijms22147717 - 19 Jul 2021
Cited by 10 | Viewed by 4371
Abstract
Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well [...] Read more.
Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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11 pages, 1487 KiB  
Review
The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer
by Matthew Martin, Mengyao Sun, Aishat Motolani and Tao Lu
Int. J. Mol. Sci. 2021, 22(14), 7429; https://doi.org/10.3390/ijms22147429 - 11 Jul 2021
Cited by 20 | Viewed by 4015
Abstract
Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. [...] Read more.
Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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15 pages, 727 KiB  
Review
Biomarkers for Cancer Cachexia: A Mini Review
by Zhipeng Cao, Kening Zhao, Irvin Jose, Nick J. Hoogenraad and Laura D. Osellame
Int. J. Mol. Sci. 2021, 22(9), 4501; https://doi.org/10.3390/ijms22094501 - 26 Apr 2021
Cited by 35 | Viewed by 8005
Abstract
Cancer cachexia is a common condition in many cancer patients, particularly those with advanced disease. Cancer cachexia patients are generally less tolerant to chemotherapies and radiotherapies, largely limiting their treatment options. While the search for treatments of this condition are ongoing, standards for [...] Read more.
Cancer cachexia is a common condition in many cancer patients, particularly those with advanced disease. Cancer cachexia patients are generally less tolerant to chemotherapies and radiotherapies, largely limiting their treatment options. While the search for treatments of this condition are ongoing, standards for the efficacy of treatments have yet to be developed. Current diagnostic criteria for cancer cachexia are primarily based on loss of body mass and muscle function. However, these criteria are rather limiting, and in time, when weight loss is noticeable, it may be too late for treatment. Consequently, biomarkers for cancer cachexia would be valuable adjuncts to current diagnostic criteria, and for assessing potential treatments. Using high throughput methods such as “omics approaches”, a plethora of potential biomarkers have been identified. This article reviews and summarizes current studies of biomarkers for cancer cachexia. Full article
(This article belongs to the Special Issue Biomarkers of Colorectal Cancer)
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