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Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition
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Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition

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: closed (20 January 2025) | Viewed by 6625

Special Issue Editor

Prof. Dr. Simona Gurzu

E-Mail Website
Guest Editor
Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 38 Gheorghe Marinescu Street, 540139 Targu Mures, Romania
Interests: oncopathology; gastric cancer; colorectal cancer; hepatocellular carcinoma; epithelial–mesenchymal transition; targeted therapy of cancer; histopathology; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The scope of this Special Issue is to collect papers referring to the biomarkers involved in the genesis, evolution, and systemic or lymphatic spread of gastrointestinal cancer. As, nowadays, targeted therapy is a hot topic, the identification of new predictive biomarkers has become mandatory in clinical practice. Any research or review-type papers that include data about tumor biomarkers, from experimental studies to clinical trials, are welcome. If some papers are mainly based on in silico analyses or examinations of public gene databases, they should include external validations of their own cohorts. We expect to receive papers focused on tissue or serum biomarkers, from protein expression to gene mutations and circulating DNA. Your individual contribution might be a step towards a better life for oncologic patients.

Prof. Dr. Simona Gurzu
Guest Editor

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Keywords

  • serum biomarkers
  • circulating DNA
  • microRNAs
  • tumor tissue
  • individualized therapy
  • gene profile
  • oncology
  • pathology
  • gastric cancer
  • colorectal cancer
  • esophageal cancer
  • carcinogenesis in oral mucosa
  • hepatocellular carcinoma
  • cholangiocarcinoma
  • pancreatic cancer
  • familial cancer

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Published Papers (4 papers)

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Research

21 pages, 8609 KiB  
Article
Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer
by Wanqian Liao, Yu Wang, Rui Wang, Bibo Fu, Xiangfu Chen, Ying Ouyang, Bing Bai, Ying Jin, Yunxin Lu, Furong Liu, Yang Zhang, Dongni Shi and Dongsheng Zhang
Int. J. Mol. Sci. 2025, 26(3), 1089; https://doi.org/10.3390/ijms26031089 - 27 Jan 2025
Viewed by 1038
Abstract
Advanced gastric cancer (AGC) is characterized by poor prognosis and limited responsiveness to immunotherapy. Tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapeutic outcomes. In this study, we developed a novel gene signature associated with M1-like TAMs using data from [...] Read more.
Advanced gastric cancer (AGC) is characterized by poor prognosis and limited responsiveness to immunotherapy. Tumor-associated macrophages (TAMs) play a pivotal role in cancer progression and therapeutic outcomes. In this study, we developed a novel gene signature associated with M1-like TAMs using data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) to predict prognosis and immunotherapy response. This gene signature was determined as an independent prognostic indicator for AGC, with high-risk patients exhibiting an immunosuppressive tumor immune microenvironment (TIME) and poorer survival outcomes. Furthermore, Interferon regulatory factor 8 (IRF8) was identified as a key gene and validated through in vitro and in vivo experiments. IRF8 overexpression reshaped the suppressive TIME, leading to an increased presence of M1-like TAMs, IFN-γ+ CD8+ T cells, and Granzyme B+ CD8+ T cells. Notably, the combination of IRF8 overexpression and anti-PD-1 therapy significantly inhibited tumor growth in syngeneic mouse models. AGC patients with elevated IRF8 expression were found to be more responsive to anti-PD-1 treatment. These findings highlight potential biomarkers for prognostic evaluation and immunotherapy in AGC, offering insights that could guide personalized treatment strategies. Full article
(This article belongs to the Special Issue Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition)
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24 pages, 7226 KiB  
Article
Bioinformatic Analysis of IKK Complex Genes Expression in Selected Gastrointestinal Cancers
by Marta Żebrowska-Nawrocka, Dagmara Szmajda-Krygier, Adrian Krygier, Agnieszka Jeleń and Ewa Balcerczak
Int. J. Mol. Sci. 2024, 25(18), 9868; https://doi.org/10.3390/ijms25189868 - 12 Sep 2024
Cited by 1 | Viewed by 1251
Abstract
Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role [...] Read more.
Gastrointestinal cancers account for over a quarter of all cancer cases and are associated with poor prognosis and high mortality rates. The IKK complex (the canonical I kappa B kinase), comprising the CHUK, IKBKB, and IKBKG genes, plays a crucial role in activating the NF-kB signaling pathway. This study aimed to analyze publicly available bioinformatics data to elucidate the oncogenic role of IKK genes in selected gastrointestinal cancers. Our findings reveal that IKBKB and IKBKG are significantly upregulated in all examined cancers, while CHUK is upregulated in esophageal carcinoma and stomach adenocarcinoma. Additionally, the expression of IKK genes varies with histological grade and nodal metastases. For instance, in stomach adenocarcinoma, CHUK and IKBKB are upregulated in higher histological grades and greater lymph node infiltration. Lower expression levels of CHUK, IKBKB, and IKBKG in stomach adenocarcinoma and IKBKB in esophageal squamous cell carcinoma correlate with shorter overall survival. Conversely, in esophageal adenocarcinoma, reduced IKBKG expression is linked to longer overall survival, while higher IKBKB expression in colon adenocarcinoma is associated with longer overall survival. Given the significant role of IKK genes in the development and progression of selected gastrointestinal cancers, they hold potential as prognostic markers and therapeutic targets, offering valuable insights for clinical practice. Full article
(This article belongs to the Special Issue Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition)
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11 pages, 1429 KiB  
Article
Gastric Carcinogenesis and Potential Role of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptor: An Observational Histopathological Study
by Sylvester R. Groen, Daniel Keszthelyi, Arpad Szallasi, Jara A. van Veghel, Annick M. E. Alleleyn, Kata Csekő, Zsuzsanna Helyes, Iryna Samarska, Heike I. Grabsch, Ad A. M. Masclee and Zsa Zsa R. M. Weerts
Int. J. Mol. Sci. 2024, 25(15), 8294; https://doi.org/10.3390/ijms25158294 - 30 Jul 2024
Viewed by 1613
Abstract
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was [...] Read more.
The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis. Full article
(This article belongs to the Special Issue Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition)
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14 pages, 5674 KiB  
Article
The Tumor Microenvironment Mediates the HIF-1α/PD-L1 Pathway to Promote Immune Escape in Colorectal Cancer
by Jing Sun, Zhengtian Zhao, Jiaqi Lu, Wen An, Yiming Zhang, Wei Li and Li Yang
Int. J. Mol. Sci. 2024, 25(7), 3735; https://doi.org/10.3390/ijms25073735 - 27 Mar 2024
Cited by 4 | Viewed by 2191
Abstract
The unsatisfactory efficacy of immunotherapy for colorectal cancer (CRC) remains a major challenge for clinicians and patients. The tumor microenvironment may promote CRC progression by upregulating the expression of hypoxia-inducing factor (HIF) and PD-L1. Therefore, this study explored the expression and correlation of [...] Read more.
The unsatisfactory efficacy of immunotherapy for colorectal cancer (CRC) remains a major challenge for clinicians and patients. The tumor microenvironment may promote CRC progression by upregulating the expression of hypoxia-inducing factor (HIF) and PD-L1. Therefore, this study explored the expression and correlation of HIF-1α and PD-L1 in the CRC microenvironment. The expression and correlation of HIF-1α and PD-L1 in CRC were analyzed using bioinformatics and Western blotting (WB). The hypoxia and inflammation of the CRC microenvironment were established in the CT26 cell line. CT26 cells were stimulated with two hypoxia mimics, CoCl2 and DFO, which were used to induce the hypoxic environment. Western blotting was used to assess the expression and correlation of HIF-1α and PD-L1 in the hypoxic environment.LPS stimulated CT26 cells to induce the inflammatory environment. WB and bioinformatics were used to assess the expression and correlation of TLR4, HIF-1α, and PD-L1 in the inflammatory environment. Furthermore, the impact of curcumin on the inflammatory environment established by LPS-stimulated CT26 cells was demonstrated through MTT, Transwell, molecular docking, network pharmacology and Western blotting assays. In this study, we found that the HIF-1α/PD-L1 pathway was activated in the hypoxic and inflammatory environment and promoted immune escape in CRC. Meanwhile, curcumin suppressed tumor immune escape by inhibiting the TLR4/HIF-1α/PD-L1 pathway in the inflammatory environment of CRC. These results suggest that combination therapy based on the HIF-1α/PD-L1 pathway can be a promising therapeutic option and that curcumin can be used as a potent immunomodulatory agent in clinical practice. Full article
(This article belongs to the Special Issue Advanced Research on Biomarkers in Gastrointestinal Cancer: 2nd Edition)
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