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Molecular Biomarkers in Cancers: Advances and Challenges

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 11533

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Special Issue Editors

Dr. Paramjit S. Tappia

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Guest Editor

Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada
Interests: cardiovascular disease; diabetes; nutrition; early-stage lung cancer
Special Issues, Collections and Topics in MDPI journals

Dr. Bram Ramjiawan

E-Mail Website
Guest Editor

Asper Clinical Research Institute, St. Boniface Hospital, Department of Pharmacology and Therapeutics Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
Interests: oncology; research; pharmacology; ethics; cancer; cardiology; diabetes; innovation; regulatory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issue, “Biomarkers for Early Detection of Cancer: Molecular Aspects”.

There are several diagnostic techniques and procedures currently used for the diagnosis of cancer. Although computed tomography, magnetic resonance imaging, and ultrasound technology are considered as gold-standard procedures for the detection of cancer, they are often associated with an undesirably high level of false positives, and they also are expensive, present accessibility issues, and involve exposure to ionizing radiation. Most of the non-imaging techniques for cancer detection are employed to corroborate biomarkers that are over-expressed in cancer cells. A number of assays have been developed to measure protein, microRNA, circulating DNA, and methylated DNA biomarkers in the blood for the detection of cancer. In addition, biopsies for molecular and biomarker diagnosis have also been utilized but are invasive and uncomfortable for patients. While these approaches are of clinical value that is more specific to late-stage cancer, they have limited value for the early detection of cancer. Accordingly, the identification of highly specific and highly selective novel molecular biomarkers for cancer diagnosis that also provide information on staging of the disease is warranted. In this Special Issue, we describe the pros and cons of current molecular approaches used in the diagnosis of cancer, as well as the technical advances in and challenges for establishing molecular biomarkers for determining the risk, detection, and progression of cancer.

Dr. Paramjit S. Tappia
Dr. Bram Ramjiawan
Guest Editors

Manuscript Submission Information

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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.

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Keywords

cancer
cancer staging
diagnostic tools
novel biomarkers
proteomics
molecular markers
metabolic profiling
prognostic value

Published Papers (6 papers)

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Research

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19 pages, 2365 KiB

Open AccessArticle

Blood-Based Epigenetic Age Acceleration and Incident Colorectal Cancer Risk: Findings from a Population-Based Case–Control Study

by Sofia Malyutina, Olga Chervova, Vladimir Maximov, Tatiana Nikitenko, Andrew Ryabikov and Mikhail Voevoda

Int. J. Mol. Sci. 2024, 25(9), 4850; https://doi.org/10.3390/ijms25094850 - 29 Apr 2024

Viewed by 247

Abstract

This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45-69) from the HAPIEE Study who had been followed up for 16 years. A nested case–control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04-1.39) to 1.44 (95% CI: 1.21-1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86-0.87 (95% CI: 0.76-0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

14 pages, 2080 KiB

Open AccessArticle

Influence of MMR, MGMT Promotor Methylation and Protein Expression on Overall and Progression-Free Survival in Primary Glioblastoma Patients Treated with Temozolomide

by Konstantin R. Brawanski, Susanne Sprung, Christian F. Freyschlag, Romana Hoeftberger, Thomas Ströbel, Johannes Haybaeck, Claudius Thomé, Claudia Manzl and Anna M. Birkl-Toeglhofer

Int. J. Mol. Sci. 2023, 24(7), 6184; https://doi.org/10.3390/ijms24076184 - 24 Mar 2023

Cited by 3 | Viewed by 1563

Abstract

Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal. Non-functional MGMT mediates the mismatch repair (MMR) system, leading to apoptosis after futile repair attempts. This study investigated the associations between MGMT promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma. MGMT promoter methylation was assessed in 42 treatment-naïve patients with glioblastoma WHO grade IV by pyrosequencing. MGMT and MMR protein expression was analyzed using immunohistochemistry. MGMT promoter methylation was present in 52%, whereas patients <70 years of age revealed a significantly longer OS using a log-rank test and a significance threshold of p ≤ 0.05. MGMT protein expression and methylation status showed no correlation. MMR protein expression was present in all patients independent of MGMT status and did not influence OS and PFS. Overall, MGMT promoter methylation implicates an improved OS in patients with glioblastoma aged <70 years. In the elderly, the extent of surgery has an impact on OS rather than the MGMT promoter methylation or protein expression. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

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Review

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13 pages, 1417 KiB

Open AccessReview

Assessing the Potential of HPV16 E6 Seroprevalence as a Biomarker for Anal Dysplasia and Cancer Screening—A Systematic Review and Meta-Analysis

by Sara Tous, Mariona Guillamet, Tim Waterboer, Laia Alemany and Sonia Paytubi

Int. J. Mol. Sci. 2024, 25(6), 3437; https://doi.org/10.3390/ijms25063437 - 19 Mar 2024

Viewed by 722

Abstract

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

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27 pages, 2878 KiB

Open AccessReview

Harnessing ADAR-Mediated Site-Specific RNA Editing in Immune-Related Disease: Prediction and Therapeutic Implications

by Shenghui Weng, Xinyi Yang, Nannan Yu, Peng-Cheng Wang, Sidong Xiong and Hang Ruan

Int. J. Mol. Sci. 2024, 25(1), 351; https://doi.org/10.3390/ijms25010351 - 26 Dec 2023

Viewed by 1477

Abstract

ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. We comprehensively review ADARs’ function as pattern recognizers and their capability to contribute to mediating immune-related pathways. We also highlight the potential role of site-specific RNA editing in maintaining homeostasis and its relationship to various diseases, such as human cancers. More importantly, we summarize the latest cutting-edge computational approaches and data resources for predicting and analyzing RNA editing sites. Lastly, we cover the recent advancement in site-directed ADAR editing tool development. This review presents an up-to-date overview of ADAR-mediated RNA editing, how site-specific RNA editing could potentially impact disease pathology, and how they could be harnessed for therapeutic applications. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

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21 pages, 1492 KiB

Open AccessReview

HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies

by Anna Pous, Lucía Notario, Cinta Hierro, Laura Layos and Cristina Bugés

Int. J. Mol. Sci. 2023, 24(14), 11403; https://doi.org/10.3390/ijms241411403 - 13 Jul 2023

Cited by 7 | Viewed by 2516

Abstract

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10–20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, this being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody–drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

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18 pages, 1074 KiB

Open AccessReview

Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers

by Vikrant Rai, Joe Abdo and Devendra K. Agrawal

Int. J. Mol. Sci. 2023, 24(4), 3316; https://doi.org/10.3390/ijms24043316 - 07 Feb 2023

Cited by 8 | Viewed by 4005

Abstract

Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The five-year survival rate of EC is less than 20%. Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular profile of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body fluids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges)

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