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Biomedicines
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Molecular Research on Colorectal Cancer
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Molecular Research on Colorectal Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 9792

Special Issue Editors

Dr. Teresa Catalano

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, via Consolare Valeria, 98125 Messina, Italy
Interests: gene expression analysis in colorectal cancer; molecular analysis in gastric and cutaneous cancers; hepatoblastomas and hepatomas
Dr. Gitana Maria Aceto

E-Mail Website
Guest Editor
Unit of Experimental Pathology, Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: molecular biology assessment methods for hereditary susceptibility, gene expression assays, and cellular and tissue phenotypic markers involved in tumor onset and progression.
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal Cancer (CRC) is the third most common malignancy in humans. The incidence of CRC varies widely around the world, as the risk of developing this disease is influenced by environmental, genetic and lifestyle factors. Currently, primary prevention and early detection appear to be necessary weapons to increase survival rates.

Many risk factors can alter the microbiome composition and deregulate immune responses by inducing inflammation. In the colonic epithelium, chronic inflammation and reactive oxygen species (ROS) production impair pathways deputed to tissue turnover and DNA damage repair through metabolic alterations in the intestinal microenvironment.

Adenomas originate from altered functional homeostasis of the intestinal epithelium and are the main precursor of CRC in both high-risk family groups and the general population. Molecular characterization of the interactions between tumor cells and the microenvironment, during tumor progression, could allow the identification of biomarkers, useful for preventive approaches to CRC.

A better comprehension of the cellular and molecular bases underlying colorectal neoplasm initiation and progression, from adenoma to metastasis, is crucial to establish non-invasive, efficient detection tests for the identification of lesions at early stages, as well as for refining the current therapeutic approaches and developing new ones useful in advanced stages of the disease.

In light of the above, in this special issue of Biomedicine on “Molecular research on colorectal cancer” we welcome original articles on translational research, clinical studies and review articles in the area of diagnostic, prognostic and predictive biomarkers in CRC.

Dr. Teresa Catalano
Dr. Gitana Maria Aceto
Guest Editors

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Keywords

  • colorectal cancer
  • molecular pathophysiology
  • environmental and genetic factors
  • microbiota tumor microenvironment
  • carcinogenesis and metastasis
  • inflammation and reactive oxygen species (ROS)
  • hereditary
  • biomarkers
  • therapeutic approaches

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Published Papers (5 papers)

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Research

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23 pages, 7967 KiB  
Article
Differential Regulation of Wingless-Wnt/c-Jun N-Terminal Kinase Crosstalk via Oxidative Eustress in Primary and Metastatic Colorectal Cancer Cells
by Gitana Maria Aceto, Sara Pagotto, Francesco Domenico Del Pizzo, Concetta Saoca, Federico Selvaggi, Rosa Visone, Roberto Cotellese, M’hammed Aguennouz, Rossano Lattanzio and Teresa Catalano
Biomedicines 2024, 12(8), 1816; https://doi.org/10.3390/biomedicines12081816 - 9 Aug 2024
Viewed by 978
Abstract
In the tumor microenvironment (TME), ROS production affects survival, progression, and therapy resistance in colorectal cancer (CRC). H2O2-mediated oxidative stress can modulate Wnt/β-catenin signaling and metabolic reprogramming of the TME. Currently, it is unclear how mild/moderate oxidative stress (eustress) [...] Read more.
In the tumor microenvironment (TME), ROS production affects survival, progression, and therapy resistance in colorectal cancer (CRC). H2O2-mediated oxidative stress can modulate Wnt/β-catenin signaling and metabolic reprogramming of the TME. Currently, it is unclear how mild/moderate oxidative stress (eustress) modulates Wnt/β-catenin/APC and JNK signaling relationships in primary and metastatic CRC cells. In this study, we determined the effects of the H2O2 concentration inducing eustress on isogenic SW480 and SW620 cells, also in combination with JNK inhibition. We assessed cell viability, mitochondrial respiration, glycolysis, and Wnt/β-catenin/APC/JNK gene and protein expression. Primary CRC cells were more sensitive to H2O2 eustress combined with JNK inhibition, showing a reduction in viability compared to metastatic cells. JNK inhibition under eustress reduced both glycolytic and respiratory capacity in SW620 cells, indicating a greater capacity to adapt to TME. In primary CRC cells, H2O2 alone significantly increased APC, LEF1, LRP6, cMYC and IL8 gene expression, whereas in metastatic CRC cells, this effect occurred after JNK inhibition. In metastatic but not in primary tumor cells, eustress and inhibition of JNK reduced APC, β-catenin, and pJNK protein. The results showed differential cross-regulation of Wnt/JNK in primary and metastatic tumor cells under environmental eustress conditions. Further studies would be useful to validate these findings and explore their therapeutic potential. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
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11 pages, 277 KiB  
Article
Association Study of IGF-1 rs35767 and rs6214 Gene Polymorphisms with Cancer Susceptibility and Circulating Levels of IGF-1, IGFBP-2, and IGFBP-3 in Colorectal Cancer Patients
by Maryam H. Alrashid, Ahmad E. Al-Serri, Rubina F. Hussain, Suzanne A. Al-Bustan and Jasem Al-Barrak
Biomedicines 2023, 11(12), 3166; https://doi.org/10.3390/biomedicines11123166 - 28 Nov 2023
Viewed by 1329
Abstract
Early detection of colorectal cancer (CRC) increases the 5-year survival rate by 90%; therefore, non-invasive biomarkers such as measurable circulating proteins for early detection and prognosis are crucial. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and apoptosis. IGF [...] Read more.
Early detection of colorectal cancer (CRC) increases the 5-year survival rate by 90%; therefore, non-invasive biomarkers such as measurable circulating proteins for early detection and prognosis are crucial. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and apoptosis. IGF binding proteins (IGFBPs) bind and inhibit the activity of IGF-1. It was inconsistently reported that high IGF-1 and IGFBP-2 and low IGFBP-3 circulating levels are associated with high cancer risk, poor prognosis, and tumor metastasis in several cancers. A total of 175 patients with CRC and 429 controls were enrolled in this study. We genotyped for IGF-1 rs35767 and rs6214 gene polymorphisms and assessed their association with circulating levels of IGF-1 and/or the risk for CRC. We also determined plasma levels of IGF-1, IGFBP-2, and IGFBP-3. Neither rs35767 nor rs2614 were associated with cancer risk or IGF-1 levels in our study cohort. IGF-1 and IGFBP-3 levels were higher in controls than in patients, whereas IGFBP-2 was higher in patients than in controls. Only IGFBP-2 was associated with increased tumor grade but not stage. Therefore, IGF-1, IGFBP-2, and IGFBP-3 may be useful as early detection and prognostic biomarkers in CRC. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
17 pages, 2479 KiB  
Article
Expression Levels of GHRH-Receptor, pAkt and Hsp90 Predict 10-Year Overall Survival in Patients with Locally Advanced Rectal Cancer
by Dávid Fodor, Éva Pozsgai, Andrew V. Schally, Zoltán László, Éva Gömöri, Éva Szabó, László Rumi, Dorottya Lőcsei, Árpád Boronkai and Szabolcs Bellyei
Biomedicines 2023, 11(3), 719; https://doi.org/10.3390/biomedicines11030719 - 27 Feb 2023
Cited by 2 | Viewed by 1436
Abstract
Background: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain [...] Read more.
Background: Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses, and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins, including growth-hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL, in specimens of locally advanced rectal cancer patients, as well as the time to metastasis and 10-year overall survival (OS) rates. We also investigated whether these outcome measures were associated with the presence of other clinical parameters. Methods: In total, 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for the proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan–Meier curves were used to show the relationships between the intensity of expression of biomarkers, clinical parameters, the time to metastasis and the 10-year OS rate. Results: High levels of p-Akt, GHRH-R and Hsp90 were associated with a significantly decreased 10-year OS rate (p = 0.001, p = 0.000, p = 0.004, respectively) and high expression levels of p-Akt and GHRH-R were correlated with a significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both a significantly longer time to metastasis and an improved 10-year OS rate. Conclusions: Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of the 10-year OS rate in locally advanced rectal cancer patients. The GHRH-R and Hsp90 expression levels were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for the anticancer treatment of advanced rectal cancer. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
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Review

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31 pages, 2035 KiB  
Review
Long Non-Coding RNAs in Colorectal Cancer: Navigating the Intersections of Immunity, Intercellular Communication, and Therapeutic Potential
by Nikolay K. Shakhpazyan, Liudmila M. Mikhaleva, Arcady L. Bedzhanyan, Nikolay K. Sadykhov, Konstantin Y. Midiber, Alexandra K. Konyukova, Andrey S. Kontorschikov, Ksenia S. Maslenkina and Alexander N. Orekhov
Biomedicines 2023, 11(9), 2411; https://doi.org/10.3390/biomedicines11092411 - 28 Aug 2023
Cited by 9 | Viewed by 2034
Abstract
This comprehensive review elucidates the intricate roles of long non-coding RNAs (lncRNAs) within the colorectal cancer (CRC) microenvironment, intersecting the domains of immunity, intercellular communication, and therapeutic potential. lncRNAs, which are significantly involved in the pathogenesis of CRC, immune evasion, and the treatment [...] Read more.
This comprehensive review elucidates the intricate roles of long non-coding RNAs (lncRNAs) within the colorectal cancer (CRC) microenvironment, intersecting the domains of immunity, intercellular communication, and therapeutic potential. lncRNAs, which are significantly involved in the pathogenesis of CRC, immune evasion, and the treatment response to CRC, have crucial implications in inflammation and serve as promising candidates for novel therapeutic strategies and biomarkers. This review scrutinizes the interaction of lncRNAs with the Consensus Molecular Subtypes (CMSs) of CRC, their complex interplay with the tumor stroma affecting immunity and inflammation, and their conveyance via extracellular vesicles, particularly exosomes. Furthermore, we delve into the intricate relationship between lncRNAs and other non-coding RNAs, including microRNAs and circular RNAs, in mediating cell-to-cell communication within the CRC microenvironment. Lastly, we propose potential strategies to manipulate lncRNAs to enhance anti-tumor immunity, thereby underlining the significance of lncRNAs in devising innovative therapeutic interventions in CRC. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
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14 pages, 1360 KiB  
Review
The Immunosuppressive Effect of TNFR2 Expression in the Colorectal Cancer Microenvironment
by Nurul Hakimah Mohd Salim, Ali Mussa, Naveed Ahmed, Suhana Ahmad, Chan Yean Yean, Rosline Hassan, Vuk Uskoković, Rohimah Mohamud and Nur Asyilla Che Jalil
Biomedicines 2023, 11(1), 173; https://doi.org/10.3390/biomedicines11010173 - 10 Jan 2023
Cited by 5 | Viewed by 2977
Abstract
Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The [...] Read more.
Colorectal cancer (CRC) represents one of the most common causes of death among cancers worldwide. Its incidence has been increasing among the young population. Many risk factors contribute to the development and progression of CRC and about 70% of them are sporadic. The CRC microenvironment is highly heterogeneous and represents a very complex immunosuppressive platform. Many cytokines and their receptors are vital participants in this immunosuppressive microenvironment. Tumor necrosis factors (TNFs) and TNF receptor 2 (TNFR2) are critical players in the development of CRC. TNFR2 was observed to have increased the immunosuppressive activity of CRC cells via regulatory T cells (T regs) and myeloid-derived suppressor cells (MDSC) in the CRC microenvironment. However, the exact mechanism of TNFR2 in regulating the CRC prognosis remains elusive. Here, we discuss the role of TNFR2 in immune escape mechanism of CRC in the immunosuppressive cells, including Tregs and MDSCs, and the complex signaling pathways that facilitate the development of CRC. It is suggested that extensive studies on TNFR2 downstream signaling must be done, since TNFR2 has a high potential to be developed into a therapeutic agent and cancer biomarker in the future. Full article
(This article belongs to the Special Issue Molecular Research on Colorectal Cancer)
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