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Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy...
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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 December 2025 | Viewed by 5209

Special Issue Editor

Dr. Ali Zaidi

E-Mail Website
Guest 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
Special Issues, Collections and Topics in MDPI journals

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

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • 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 (6 papers)

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Research

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22 pages, 3052 KB  
Article
Evaluation of Spectral Imaging for Early Esophageal Cancer Detection
by Li-Jen Chang, Chu-Kuang Chou, Arvind Mukundan, Riya Karmakar, Tsung-Hsien Chen, Syna Syna, Chou-Yuan Ko and Hsiang-Chen Wang
Cancers 2025, 17(12), 2049; https://doi.org/10.3390/cancers17122049 - 19 Jun 2025
Viewed by 711
Abstract
Objective: Esophageal carcinoma (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. Early detection is vital for improving prognosis, particularly for dysplasia and squamous cell carcinoma (SCC). Methods: This study evaluates a hyperspectral imaging conversion method, [...] Read more.
Objective: Esophageal carcinoma (EC) is the eighth most prevalent cancer and the sixth leading cause of cancer-related mortality worldwide. Early detection is vital for improving prognosis, particularly for dysplasia and squamous cell carcinoma (SCC). Methods: This study evaluates a hyperspectral imaging conversion method, the Spectrum-Aided Vision Enhancer (SAVE), for its efficacy in enhancing esophageal cancer detection compared to conventional white-light imaging (WLI). Five deep learning models (YOLOv9, YOLOv10, YOLO-NAS, RT-DETR, and Roboflow 3.0) were trained and evaluated on a dataset comprising labeled endoscopic images, including normal, dysplasia, and SCC classes. Results: Across all five evaluated deep learning models, the SAVE consistently outperformed conventional WLI in detecting esophageal cancer lesions. For SCC, the F1 score improved from 84.3% to 90.4% in regard to the YOLOv9 model and from 87.3% to 90.3% in regard to the Roboflow 3.0 model when using the SAVE. Dysplasia detection also improved, with the precision increasing from 72.4% (WLI) to 76.5% (SAVE) in regard to the YOLOv9 model. Roboflow 3.0 achieved the highest F1 score for dysplasia of 64.7%. YOLO-NAS exhibited balanced performance across all lesion types, with the dysplasia precision rising from 75.1% to 79.8%. Roboflow 3.0 also recorded the highest SCC sensitivity of 85.7%. In regard to SCC detection with YOLOv9, the WLI F1 score was 84.3% (95% CI: 71.7–96.9%) compared to 90.4% (95% CI: 80.2–100%) with the SAVE (p = 0.03). For dysplasia detection, the F1 score increased from 60.3% (95% CI: 51.5–69.1%) using WLI to 65.5% (95% CI: 57.0–73.8%) with SAVE (p = 0.04). These findings demonstrate that the SAVE enhances lesion detectability and diagnostic performance across different deep learning models. Conclusions: The amalgamation of the SAVE with deep learning algorithms markedly enhances the detection of esophageal cancer lesions, especially squamous cell carcinoma and dysplasia, in contrast to traditional white-light imaging. This underscores the SAVE’s potential as an essential clinical instrument for the early detection and diagnosis of cancer. Full article
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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18 pages, 7757 KB  
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 664
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
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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13 pages, 1624 KB  
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 650
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
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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19 pages, 3338 KB  
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
Viewed by 1188
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
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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Review

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14 pages, 1056 KB  
Review
Beyond Detection: Conventional and Emerging Biomarkers in Gastrointestinal Cancers
by Daniel M. Han, Mark R. Wakefield and Yujiang Fang
Cancers 2025, 17(17), 2725; https://doi.org/10.3390/cancers17172725 - 22 Aug 2025
Viewed by 548
Abstract
Gastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and [...] Read more.
Gastrointestinal (GI) cancers, particularly colorectal and gastric cancers, majorly contribute to global cancer mortality due to frequent late-stage diagnosis and poor therapeutic response in advanced disease. Earlier detection of GI cancers is needed for a better prognosis. This review examines both traditional and emerging biomarkers that contribute significantly to early detection, prognostication, and prediction of therapeutic resistance or sensitivity. Specifically, we highlight the diagnostic utility of non-invasive liquid biopsy biomarkers such as circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes. Moreover, we discuss the prognostic and predictive value of conventional genetic alterations, including KRAS, BRAF, and HER2. Although new findings have shown the advantages of liquid biopsy over colonoscopy, there are still limitations to the technique, such as cost-effectiveness, technological gaps in low-resource settings, and uncertain detection rates. Further studies are required to test the validity and accessibility of liquid biopsy and its biomarkers in order to advance personalized diagnosis and treatments for GI cancers. Such a study will be helpful for clinicians to better manage patients with GI cancers. Full article
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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40 pages, 480 KB  
Review
The Role of Epigenetic Biomarkers as Diagnostic, Predictive and Prognostic Factors in Colorectal Cancer
by Zuzanna Chilimoniuk, Konrad Gładysz, Natalia Moniczewska, Katarzyna Chawrylak, Zuzanna Pelc and Radosław Mlak
Cancers 2025, 17(16), 2632; https://doi.org/10.3390/cancers17162632 - 12 Aug 2025
Viewed by 645
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations [...] Read more.
Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting SDC2 and SEPT9 in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like LINE-1, mSEPT9 and ERCC1 have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of NKX6.1, IGFBP3, and LMX1A has been identified as an independent negative prognostic factor, while SFRP2 hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups. Full article
(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)
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