Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 13 June 2025 | Viewed by 1954

Special Issue Editor

Esophageal and Lung Institute, Allegheny Health Network Institute, Pittsburgh, PA 15212, USA
Interests: esophageal cancer; development therapeutics; precision medicine; lung cancer; surveillance; early detection; disease monitoring; treatment response and immunotherapy
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Special Issue Information

Dear Colleagues,

In recent years, cancer biomarkers have played a critical role in promoting personalized medicine and improving outcomes for patients with cancer by addressing critical unmet needs in their clinical management paradigms. In this context, biomarker-based cancer diagnosis is budding as one of the most promising ways for early detection, recurrence detection, disease progression monitoring, and effective cancer therapy. Gastrointestinal cancers account for 26% of the global cancer incidence burden and 35% of all cancer-related deaths. According to the World Health Organization, in 2018, there were an estimated 4.8 million new cases of cancer and 3.4 million related deaths worldwide. Therefore, the urgent development of novel and accurate biomarkers is necessary for enhancing screening and early detection, to better predict prognosis and identify novel therapeutic targets.

This Special Issue focuses on the need to find more meaningful gastrointestinal cancer biomarkers and druggable targets based on originality, importance, and timeliness. We welcome original research, reviews and clinical trials related but not limited to the following aspects:

  • Development of novel screening and early detection biomarkers—SCED and MCED approaches;
  • Identification and validation of clinically significant novel biomarkers to predict therapy response and prognosis of gastrointestinal cancer;
  • Data analysis and validation identifying the novel features of gastrointestinal cancer to better guide future treatment;
  • Underlying mechanisms of recurrence or metastasis of gastrointestinal cancer;
  • Identification of therapeutic targets in gastrointestinal cancers.

We look forward to hearing from you.

Dr. Ali Zaidi
Guest Editor

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Keywords

  • liquid biopsy
  • esophageal cancer
  • gastric cancer
  • colorectal cancer
  • pancreatic cancer
  • hepatocellular cancer
  • appendiceal cancer
  • cancer biomarker
  • DNA sequencing
  • transcriptomics
  • proteomics
  • immunohistochemistry

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Published Papers (3 papers)

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Research

18 pages, 7757 KiB  
Article
Modeling the Transitional Phase of Epithelial Cells Reveals Prognostic and Therapeutic Targets in Pancreatic Ductal Adenocarcinoma
by Linhan Ye, Zongyao Chen, Jingcheng Zhang and Qiaolin Li
Cancers 2025, 17(11), 1813; https://doi.org/10.3390/cancers17111813 - 29 May 2025
Viewed by 246
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression is driven by epithelial plasticity and tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from the early stage to the aggressive phase would [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression is driven by epithelial plasticity and tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from the early stage to the aggressive phase would facilitate clinical management. Method: In this study, we employed single-cell RNA sequencing to characterize a distinct subpopulation of highly proliferative epithelial cells undergoing a transitional phase during PDAC progression. By linking to cell cycle dysregulation, epithelial differentiation, and clinical staging, we constructed a gene-based risk score model using Lasso Cox regression. The expression of selected genes within the model was further validated using qPCR. Results: The model demonstrated robust predictive power for patient prognosis, TNM staging, and chemotherapy sensitivity. Further analysis of the tumor microenvironment revealed intensified crosstalk between a specific fibroblast subpopulation and transitional epithelial cells, mediated largely by collagen signaling. This stromal–epithelial interaction was found to contribute to the fibrotic barrier characteristic of PDAC. Additionally, immune profiling uncovered altered infiltration patterns, particularly involving natural killer (NK) cells in high-risk patients, suggesting mechanisms of immune tolerance and inhibition. Conclusions: These findings offer potential avenues for early detection, risk stratification, and targeted therapeutic strategies in PDAC. Full article
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14 pages, 1624 KiB  
Article
Proportional Correlation Between Systemic Inflammation Response Index and Gastric Cancer Recurrence Time: A Retrospective Study
by Kyungryun In, Sunhyung Kang, Hyunseok Lee, Hyuksoo Eun, Heeseok Moon, Eaumseok Lee, Seokhyun Kim, Jaekyu Sung and Byungseok Lee
Cancers 2025, 17(9), 1415; https://doi.org/10.3390/cancers17091415 - 23 Apr 2025
Viewed by 301
Abstract
Background: Disease recurrence is the primary cause of death in patients with gastric cancer who have undergone complete surgical resection. No prognostic factors for recurrence, other than the Tumor, Node, and Metastasis stage, have been established. However, recurrence rates differ even within the [...] Read more.
Background: Disease recurrence is the primary cause of death in patients with gastric cancer who have undergone complete surgical resection. No prognostic factors for recurrence, other than the Tumor, Node, and Metastasis stage, have been established. However, recurrence rates differ even within the same Tumor, Node, and Metastasis stage. Therefore, we aimed to develop a new prognostic confidence measure for gastric cancer recurrence and demonstrate its practical utility. Methods: This was a retrospective study based on the medical records of the Chungnam National University Hospital, Republic of Korea. We enrolled patients diagnosed with stage II/III gastric cancer who underwent complete surgical resection and adjuvant chemotherapy over the past 12 years. The association between seven variables, including the systemic inflammation response index (SIRI) and gastric cancer recurrence, was analyzed. Results: A total of 296 patients were enrolled in this study. Although other factors did not exhibit significant correlations, SIRI showed a significant positive correlation with gastric cancer recurrence risk, confirmed through Cox regression testing (hazard ratio, 1.231; 95% confidence interval, 1.04–1.45). Linear regression analysis revealed a significant association between higher SIRI values and shorter recurrence time (p = 0.044; β = −0.225). Conclusions: In this study, other than SIRI, effective prognostic factors related to gastric cancer recurrence were not verified, thus indicating SIRI as a potential independent prognostic factor. Full article
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19 pages, 3338 KiB  
Article
Intra-Tumoral CD8+:CD3+ Lymphocyte Density Ratio in Appendix Cancer Is a Tumor Volume- and Grade-Independent Predictor of Survival
by Chelsea Knotts, Hyun Park, Christopher Sherry, Rose Blodgett, Catherine Lewis, Ashten Omstead, Kunhong Xiao, William LaFramboise, David L. Bartlett, Neda Dadgar, Ajay Goel, Ali H. Zaidi and Patrick L. Wagner
Cancers 2025, 17(3), 542; https://doi.org/10.3390/cancers17030542 - 6 Feb 2025
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Abstract
Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by [...] Read more.
Background: The immune contexture of solid tumors plays a critical role in cancer progression and response to immunotherapy. However, immunologic characterization of appendiceal cancer (AC) has lagged behind advancements in other gastrointestinal malignancies. This study aims to define the AC immune microenvironment by quantifying CD3+ and CD8+ lymphocyte densities and assessing their prognostic significance. Methods: Archival tissue samples from 95 AC patients were analyzed using immunohistochemistry to assess CD3+ and CD8+ T cell densities and their ratios. Associations between lymphocyte density and clinical, pathologic, and oncologic variables were examined using Spearman’s correlation, Kruskal–Wallis tests, and Cox proportional hazards analysis. Results: Tumor samples exhibited substantial immunologic heterogeneity with significant rightward skew. CD3+ and CD8+ densities were higher in low-grade tumors (p = 0.02 and p = 0.01, respectively) and low-grade histologic subtypes (p = 0.01 and p = 0.006). Lymphocyte density was inversely associated with patient age and was significantly lower in high-grade and non-mucinous tumors. The CD8+:CD3+ ratio emerged as an independent prognostic marker for progression-free survival (HR = 0.39, p = 0.004), whereas absolute CD3+ and CD8+ densities were less predictive. Conclusions: This study highlights the diverse immune microenvironment in AC, with immune infiltration patterns correlating with tumor grade and histologic subtype. The CD8+:CD3+ ratio is a potential prognostic biomarker for patient stratification, underscoring its clinical significance. Future studies should expand immune biomarker panels and explore immunomodulatory therapies for lymphocyte-rich AC subsets. Full article
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