Colorectal and Gastric Cancers: Molecular Mechanisms and Potential Biomarkers

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biomarkers".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 7679

Special Issue Editors


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Guest Editor
1. Institute of Gastrointestinal Oncology, Military University Hospital Prague, Prague, Czech Republic
2. Department of Medicine, First Faculty of Medicine, Charles University, Prague and Military University Hospital Prague, Prague, Czech Republic
3. Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
Interests: colorectal cancer; gastroenterology; gastric cancer; pancreatic cancer
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Guest Editor
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
Interests: metabolomics; mass spectrometry; biogerontology; colon cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer is the third most common malignancy and the second leading cause of cancer-related deaths in the world, with a yearly estimated number of roughly 2 million new cases and about 900 thousand deaths worldwide. Despite all the progress made in basic science, clinical research and translation medicine within recent years, the molecular mechanisms of colorectal cancer have not been fully understood. They include genetics, metabolomic issues and several immunology aspects. The gastrointestinal microbiome plays a crucial role in the pathogenesis of colorectal cancer, and the identification of a clearly reliable composition of "beneficial" or "hazardous" colonic microbiota is still pending. There is an insistent need for further studies on factors influencing the micro-environment of the gastrointestinal tract (diet, xenobiotics, bile acids and other signalling molecules, luminal pH and others).

Gastric cancer was the fifth most common malignant tumour in the world in 2020, with approximately 1.1 million new cases, causing 800,000 deaths per year. It comprises cardia and non-cardia gastric cancer and newly recognized diseases (e.g., GAPPS—gastric adenocarcinoma and proximal polyposis of the stomach). The International Agency for Research on Cancer estimated that about one-third (350,000 cases per year) of all sporadic non-cardia gastric cancers are solely attributed to chronic Helicobacter pylori infection. Possible positive or negative association of Helicobacter pylori and cardia gastric cancer has been intensively investigated in recent years. Unlike sporadic non-cardia gastric cancer, Helicobacter pylori is usually absent in patients with GAPPS. Although there is an inverse association between GAPPS and Helicobacter pylori infection, only little data on this association are available so far.

Fully reliable biomarkers are still missing. These markers should be determinative for the identification of cancer risk factors (both in high-risk and average-risk populations) and should cover the progression from premalignant lesions to cancer, the dependability of early diagnosis, staging and grading, the prediction of response to treatment and the side effects of oncology therapy (including immunopathology-associated complications, infections, bile acid malabsorption, small intestinal bacterial overgrowth and others). Artificial intelligence should be also implemented, employing advanced methods (e.g., data-mining, artificial neural network and others).

The concept of predictive, preventive and personalized medicine (3PM) is a new approach that is an important revolution in the field of modern medicine that combines advanced medical investigation and technologies and data analytics to predict and prevent diseases and provide personalised treatment to each individual. The potential biomarkers of gastric and colorectal cancer are important and promising parts of the 3PM concept.

Researchers are invited to consider submitting papers on the burning topics mentioned above.

Dr. Jan Bures
Dr. Nicholas J. W. Rattray
Guest Editors

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Keywords

  • colorectal cancer
  • gastric cancer
  • molecular mechanism
  • biomarkers signalling
  • molecules gastrointestinal
  • microbiome
  • artificial intelligence

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Published Papers (5 papers)

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Research

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14 pages, 2345 KiB  
Article
Transcript PHF19-207 May Be a Long Non-Coding RNA with Tumor-Promoting Role in Colon Cancer
by Dunja Pavlovic, Tamara Babic, Sofija Ignjatovic, Katarina Pavlovic, Sandra Dragicevic and Aleksandra Nikolic
Biomolecules 2025, 15(7), 957; https://doi.org/10.3390/biom15070957 - 2 Jul 2025
Viewed by 295
Abstract
Recent pan-cancer transcriptome analysis has revealed differential activity of two alternative PHF19 gene promoters in malignant versus non-malignant gut mucosa. One of these promoters upregulated in colon cancer leads to the expression of the PHF19-207 transcript, suggesting its potential role in tumor promotion. [...] Read more.
Recent pan-cancer transcriptome analysis has revealed differential activity of two alternative PHF19 gene promoters in malignant versus non-malignant gut mucosa. One of these promoters upregulated in colon cancer leads to the expression of the PHF19-207 transcript, suggesting its potential role in tumor promotion. The objective of this study was to investigate the function of PHF19-207 using in silico tools and publicly available data, as well as to assess its expression in colon cancer. Expression analyses were conducted via qPCR and RNA sequencing on RNA extracted from the immortalized colonic epithelial cell line HCEC-1CT, as well as a series of colon cancer cell lines cultured in both 2D and 3D environments. The expression of PHF19-207 was found to be elevated in all malignant cell lines compared to the non-malignant HCEC-1CT cell line in both culture conditions, with the most prominent increase observed in cell lines derived from advanced stages of the disease and in the HCEC-1CT cell line overexpressing KRAS. Furthermore, the PHF19-207 transcript was detected in exosomes derived from malignant cells. These findings suggest that PHF19-207 holds potential as a diagnostic biomarker. In addition, in silico analyses indicate that this transcript may function as a long non-coding RNA involved in the regulation of gene expression. Further functional investigations are required to elucidate its precise role in colon carcinogenesis. Full article
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25 pages, 6856 KiB  
Article
The Proapoptotic Effect of MB-653 Is Associated with the Modulation of Metastasis and Invasiveness-Related Signalling Pathways in Human Colorectal Cancer Cells
by Libor Sokoli, Peter Takáč, Mariana Budovská, Radka Michalková, Martin Kello, Natália Nosálová, Ľudmila Balážová, Šimon Salanci and Ján Mojžiš
Biomolecules 2025, 15(1), 72; https://doi.org/10.3390/biom15010072 - 6 Jan 2025
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Abstract
Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing [...] Read more.
Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC50 values of 5.8 ± 0.3 μmol/L for HCT116 cells and 6.1 ± 2.1 μmol/L for Caco2 cells. Flow cytometry and Western blot analysis were employed to investigate the molecular mechanisms underlying cytotoxicity, proapoptotic action, and anti-invasion effects. The proapoptotic activity was evidenced by the activation of caspases 3 and 7, mitochondrial dysfunction, and an increased number of apoptotic cells, confirmed by annexin V/PI and AO/PI staining. Additionally, MB-653 induces dose-dependent G2/M phase cell cycle arrest, the cause of which could be cyclin B1/CDC2 complex dysfunction and/or a decrease in α-tubulin protein expression. Another important observation was that MB-653 modulated several signalling pathways associated with various cellular activities, including survival, proliferation, tumour invasiveness, metastasis, and epithelial–mesenchymal transition (EMT). We further demonstrated its safety for topical and parenteral application. To sum up, our results indicate the real potential of MB-653 in treating colorectal cancer. Full article
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12 pages, 4071 KiB  
Article
IL6 and IL6R as Prognostic Biomarkers in Colorectal Cancer
by Kathryn A. F. Pennel, Ahmad Kurniawan, Sara Samir Foad Al-Badran, Leonor Schubert Santana, Jean Quinn, Colin Nixon, Phimmada Hatthakarnkul, Noori Maka, Campbell Roxburgh, Donald McMillan and Joanne Edwards
Biomolecules 2024, 14(12), 1629; https://doi.org/10.3390/biom14121629 - 19 Dec 2024
Cited by 1 | Viewed by 1556
Abstract
Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is [...] Read more.
Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome. However, evidence is more limited for the role of IL6 and its cognate receptor, IL6R, within the tumour epithelium and microenvironment. This study aimed to investigate IL6 and IL6R expression in a large cohort of retrospectively collected patient tumour specimens and determine association with clinical outcomes and characteristics. High expression of IL6R in the tumour epithelium was associated with reduced cancer-specific survival in patients with right-sided colon cancer. In these patients, high IL6R expression was also associated with an increased systemic neutrophil-to-lymphocyte ratio. A high number of copies of IL6 mRNA within the tumour-associated stroma, but not epithelium, was associated with reduced cancer-specific survival. The results from this study have validated IL6R as a marker of poor prognosis in a subgroup of CRC patients and identified the spatially resolved prognostic nature of intra-tumoural IL6 expression. This study has also highlighted the need for investigation of IL6/IL6R-targeted therapies as novel treatment strategies for patients with colon cancer. Full article
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Review

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28 pages, 1513 KiB  
Review
The Impact of the Microbiota on the Immune Response Modulation in Colorectal Cancer
by Ana Iulia Neagu, Marinela Bostan, Vlad Alexandru Ionescu, Gina Gheorghe, Camelia Mia Hotnog, Viviana Roman, Mirela Mihaila, Simona Isabelle Stoica, Camelia Cristina Diaconu, Carmen Cristina Diaconu, Simona Maria Ruta and Coralia Bleotu
Biomolecules 2025, 15(7), 1005; https://doi.org/10.3390/biom15071005 - 14 Jul 2025
Viewed by 485
Abstract
Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis—dysbiosis—has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide [...] Read more.
Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis—dysbiosis—has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8+ T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies—ranging from dietary interventions and prebiotics to fecal microbiota transplantation (FMT) and microbial consortia—as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome-informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms. Full article
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19 pages, 1135 KiB  
Review
Intratumoral Microbiota: Metabolic Influences and Biomarker Potential in Gastrointestinal Cancer
by Xueyuan Bi, Jihan Wang and Cuicui Liu
Biomolecules 2024, 14(8), 917; https://doi.org/10.3390/biom14080917 - 27 Jul 2024
Cited by 5 | Viewed by 2890
Abstract
Gastrointestinal (GI) cancers impose a substantial global health burden, highlighting the necessity for deeper understanding of their intricate pathogenesis and treatment strategies. This review explores the interplay between intratumoral microbiota, tumor metabolism, and major types of GI cancers (including esophageal, gastric, liver, pancreatic, [...] Read more.
Gastrointestinal (GI) cancers impose a substantial global health burden, highlighting the necessity for deeper understanding of their intricate pathogenesis and treatment strategies. This review explores the interplay between intratumoral microbiota, tumor metabolism, and major types of GI cancers (including esophageal, gastric, liver, pancreatic, and colorectal cancers), summarizing recent studies and elucidating their clinical implications and future directions. Recent research revealed altered microbial signatures within GI tumors, impacting tumor progression, immune responses, and treatment outcomes. Dysbiosis-induced alterations in tumor metabolism, including glycolysis, fatty acid metabolism, and amino acid metabolism, play critical roles in cancer progression and therapeutic resistance. The integration of molecular mechanisms and potential biomarkers into this understanding further enhances the prognostic significance of intratumoral microbiota composition and therapeutic opportunities targeting microbiota-mediated tumor metabolism. Despite advancements, challenges remain in understanding the dynamic interactions within the tumor microenvironment (TME). Future research directions, including advanced omics technologies and prospective clinical studies, offer promising avenues for precision oncology and personalized treatment interventions in GI cancer. Overall, integrating microbiota-based approaches and molecular biomarkers into GI cancer management holds promise for improving patient outcomes and survival. Full article
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