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Diagnostics
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Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction
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Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 11688

Special Issue Editor

Dr. Alexander R. Siebenhüner

E-Mail Website
Guest Editor
Department of Hematology & Oncology, Hirslanden Zürich, 8032 Zürich, Switzerland
Interests: gastric cancer; colorectal cancer; gastroenteropancreatic neuroendocrine tumors

Special Issue Information

Dear Colleagues, 

Gastrointestinal cancer is a complex of heterogenous tumors. However, in the past, gastric cancer and, in some way, colorectal cancer (CRC) have been widely treated through a general chemotherapy combination without differentiation of molecular subtypes. While the addition of antibodies targeting antivascular endothelial factors (aVGFR) has been achieved some effort in the general colorectal cancer population in the metastatic setting, the effect of epithermal growth factor (EGFR) antibodies has shown a positive predictive outcome in the RAS wild-type population. In contrast, aEGFR antibodies have been a negative predictive marker in the RAS mutated CRC population, which is now depicted in the current guidelines. This is only one example of prognostication in the CRC setting, and more molecular-driven strategies have been detected in recent years. This knowledge has also emerged in the molecular understanding of gastric cancer (GC), while the addition of immune scores has been found to help to better select the patient population for more precise GC treatment. This means that we are now one step closer to a better understanding of the tumor and its interaction with the microenvironment. Therefore, additional knowledge must be gathered, especially in diagnostics via imaging, ctDNA, and detection of molecular-driven resistance to our therapy. These steps will help toward a more precise understanding of the individual tumor setup in the field of gastrointestinal cancers as well improve survival in this challenging format.

Dr. Alexander R. Siebenhüner
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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

  • colorectal cancer
  • gastric cancer
  • biomarkers
  • imaging
  • ctDNA

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Published Papers (4 papers)

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Research

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12 pages, 1052 KiB  
Article
KRAS Mutational Profiles among Colorectal Cancer Patients in the East Coast of Peninsular Malaysia
by Hidayati Husainy Hasbullah, Sarina Sulong, Nur Asyilla Che Jalil, Ahmad Aizat Abdul Aziz, Nurfadhlina Musa and Marahaini Musa
Diagnostics 2023, 13(5), 822; https://doi.org/10.3390/diagnostics13050822 - 21 Feb 2023
Cited by 5 | Viewed by 1771
Abstract
Background: KRAS is a key driver gene in colorectal carcinogenesis. Despite this, there are still limited data on the mutational status of KRAS amongst colorectal cancer (CRC) patients in Malaysia. In the present study, we aimed to analyze the KRAS mutational profiles on [...] Read more.
Background: KRAS is a key driver gene in colorectal carcinogenesis. Despite this, there are still limited data on the mutational status of KRAS amongst colorectal cancer (CRC) patients in Malaysia. In the present study, we aimed to analyze the KRAS mutational profiles on codons 12 and 13 amongst CRC patients in Hospital Universiti Sains Malaysia, Kelantan, located on the East Coast of Peninsular Malaysia. Methods: DNA were extracted from formalin-fixed, paraffin-embedded tissues obtained from 33 CRC patients diagnosed between 2018 and 2019. Amplifications of codons 12 and 13 of KRAS were conducted using conventional polymerase chain reaction (PCR) followed by Sanger sequencing. Results: Mutations were identified in 36.4% (12/33) of patients, with G12D (50%) being the most frequent single-point mutation observed, followed by G12V (25%), G13D (16.7%), and G12S (8.3%). No correlation was found between mutant KRAS and location of the tumor, staging, and initial carcinoembryonic antigen (CEA) level. Conclusion: Current analyses revealed that a significant proportion of CRC patients in the East Coast of Peninsular Malaysia have KRAS mutations, where this frequency is higher compared to those in the West Coast. The findings of this study would serve as a precursor for further research that explores KRAS mutational status and the profiling of other candidate genes among Malaysian CRC patients. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction)
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14 pages, 2805 KiB  
Article
NCR, an Inflammation and Nutrition Related Blood-Based Marker in Colon Cancer Patients: A New Promising Biomarker to Predict Outcome
by Melanie Langheinrich, Alexander Reinhard Siebenhüner, Justus Baecker, Maximilian Miragall, Felix Wiesmüller, Vera Schellerer, Susanne Merkel, Maximilian Brunner, Christian Krautz, Klaus Weber, Robert Grützmann and Stephan Kersting
Diagnostics 2023, 13(1), 116; https://doi.org/10.3390/diagnostics13010116 - 30 Dec 2022
Cited by 2 | Viewed by 2794
Abstract
Background: Colorectal carcinoma (CRC) is a heterogeneous disease, and differences in outcomes have been reported among patients diagnosed with the same disease stage. Prognostic and predictive biomarkers provide information for patient risk stratification and guide treatment selection. Although numerous studies have analyzed the [...] Read more.
Background: Colorectal carcinoma (CRC) is a heterogeneous disease, and differences in outcomes have been reported among patients diagnosed with the same disease stage. Prognostic and predictive biomarkers provide information for patient risk stratification and guide treatment selection. Although numerous studies have analyzed the effects of systemic inflammatory factors on CRC outcomes, clinical significance remains to be elucidated. In particular, the treatment strategy of colon cancer patients is different from that of rectal cancer due to outcome and recurrence differences. The identification of patients with a poor prognosis who might benefit from intensive treatment approaches is clinically necessary. Methods: This study aimed to evaluate the value of different blood-based markers and assess the significance of our newly developed inflammatory-nutrition-related biomarker (NCR = BMI × albumin/CRP) in patients with colon cancer. A two-stage design was used with 212 patients with colon cancer (CC) in the discovery cohort (n = 159) and in an external validation cohort (n = 53). Results: A lower preoperative NCR level was significantly correlated with a worse prognosis, sidedness, undifferentiated histology, nodal involvement, and advanced UICC stage. We compared the NCR with other established prognostic indices and showed that the NCR is a more reliable indicator of a poor prognosis for patients with CC. Patients with low NCR levels experienced a significantly shorter Overall Survival (OS) than patients with high levels. Multivariate analysis confirmed preoperative NCR levels as an independent predictor for overall survival with a hazard ratio of 3.3 (95% confidence interval 1.628–6.709, p < 0.001). Finally, we confirmed the predictive value of the NCR in an independent validation cohort and confirmed NCR as an independent prognostic factor for OS. Conclusion: Taken together, we discovered a new prognostic index (NCR) based on BMI, albumin, and CRP levels as an independent prognostic predictor of OS in patients with colon cancer. In all UICC stages, our newly developed NCR marker is able to distinguish patients with better and worse prognoses. We, therefore, propose that NCR may serve as a supplement to the TNM staging system to optimize the risk stratification in CC patients towards personalized oncology. In particular, NCR can be used in clinical trials to stratify patients with UICC II and III tumors and help better select patients who might benefit from adjuvant treatment. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction)
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Review

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14 pages, 862 KiB  
Review
Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
by Moonsik Kim, Ji Yun Jeong and An Na Seo
Diagnostics 2023, 13(17), 2782; https://doi.org/10.3390/diagnostics13172782 - 28 Aug 2023
Cited by 3 | Viewed by 2218
Abstract
Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Unfortunately, molecular heterogeneity and, consequently, acquired resistance in GC are the major causes of failure in the development of biomarker-guided targeted [...] Read more.
Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Unfortunately, molecular heterogeneity and, consequently, acquired resistance in GC are the major causes of failure in the development of biomarker-guided targeted therapies. However, by showing promising survival benefits in some studies, the recent emergence of immunotherapy in GC has had a significant impact on treatment-selectable procedures. Immune checkpoint inhibitors (ICIs), widely indicated in the treatment of several malignancies, target inhibitory receptors on T lymphocytes, including the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and release effector T-cells from negative feedback signals. In this article, we review currently available predictive biomarkers (including PD-L1, microsatellite instability, Epstein–Barr virus, and tumor mutational burden) that affect the ICI treatment response, focusing on PD-L1 expression. We further briefly describe other potential biomarkers or mechanisms for predicting the response to ICIs in GC. This review may facilitate the expansion of the understanding of biomarkers for predicting the response to ICIs and help select the appropriate therapeutic approaches for patients with GC. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction)
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15 pages, 1231 KiB  
Review
Current Concepts of Precancerous Lesions of Hepatocellular Carcinoma: Recent Progress in Diagnosis
by Ziyue Liao, Cuiping Tang, Rui Luo, Xiling Gu, Jun Zhou and Jian Gao
Diagnostics 2023, 13(7), 1211; https://doi.org/10.3390/diagnostics13071211 - 23 Mar 2023
Cited by 5 | Viewed by 4221
Abstract
The most common cause of hepatocellular carcinoma (HCC) is chronic hepatitis and cirrhosis. It is proposed that precancerous lesions of HCC include all stages of the disease, from dysplastic foci (DF), and dysplastic nodule (DN), to early HCC (eHCC) and progressed HCC (pHCC), [...] Read more.
The most common cause of hepatocellular carcinoma (HCC) is chronic hepatitis and cirrhosis. It is proposed that precancerous lesions of HCC include all stages of the disease, from dysplastic foci (DF), and dysplastic nodule (DN), to early HCC (eHCC) and progressed HCC (pHCC), which is a complex multi-step process. Accurately identifying precancerous hepatocellular lesions can significantly impact the early detection and treatment of HCC. The changes in high-grade dysplastic nodules (HGDN) were similar to those seen in HCC, and the risk of malignant transformation significantly increased. Nevertheless, it is challenging to diagnose precancerous lesions of HCC. We integrated the literature and combined imaging, pathology, laboratory, and other relevant examinations to improve the accuracy of the diagnosis of precancerous lesions. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Diagnosis, Prognosis and Therapy Response Prediction)
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