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Special Issue "Molecular Alterations in GastroIntestinal Pre-invasive Lesions"

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: 31 December 2021.

Special Issue Editors

Prof. Dr. Luca Saragoni
E-Mail Website
Guest Editor
Department of Pathology, G.B.Morgagni–L.Pierantoni Hospital, Forlì, Italy
Interests: gastrointestinal pathology; gastric cancer
Prof. Dr. Matteo Fassan
E-Mail Website
Guest Editor
Educational Dean of the Degree Course in Biomedical Laboratory Techniques, School of Medicine and Surgery, University of Padua, Padua (PD), Italy
Interests: colorectal cancer; gastric cancer; dysplasia; molecular carcinogenesis; predictive biomarkers
Special Issues and Collections in MDPI journals

Special Issue Information

Dear colleguaes,

The relatively recent comprehensive molecular characterization of gastrointestinal tumors has demonstrated that similar oncogenetic pathways are shared among different types of cancers. This represents the biological rationale for the development and introduction into clinical practice of targeted therapies and for the optimization of the already available chemotherapeutic drugs. Moreover, significant intra-tumor genomic and epigenomic heterogeneity has been observed, resulting in the identification of new specific and sensitive predictive and prognostic biomarkers and in innovative molecular classifications based on gene expression profiling. Despite these important information, complete molecular data on pre-invasive lesions of the gastrointestinal tract are still limited, significantly affecting the diagnostic process and treatment of gastrointestinal “early” lesions. The research topic aims to study: (i) the clinico-pathological features and their matched molecular characteristics distinguishing pre-invasive (early) gastrointestinal lesions; (ii) the identification of novel molecular markers, which can be useful in the identification of the neoplastic precursors/preinvasive lesions; (iii) the identification of novel molecular biomarkers to be implemented in the secondary prevention strategies of invasive gastrointestinal tumors.

Prof. Dr. Luca Saragoni
Prof. Dr. Matteo Fassan
Guest Editors

Manuscript Submission Information

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Keywords

  • gastrointestinal cancer
  • early diagnosis
  • molecular markers
  • non-invasive treatments.

Published Papers (6 papers)

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Research

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Article
The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence
Int. J. Mol. Sci. 2021, 22(18), 9791; https://doi.org/10.3390/ijms22189791 - 10 Sep 2021
Viewed by 302
Abstract
Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune [...] Read more.
Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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Review

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Review
Molecular Landscapes of Gastric Pre-Neoplastic and Pre-Invasive Lesions
Int. J. Mol. Sci. 2021, 22(18), 9950; https://doi.org/10.3390/ijms22189950 - 14 Sep 2021
Viewed by 347
Abstract
Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, [...] Read more.
Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. In this review, we describe the landscape of molecular alterations in gastric pre-invasive lesions with a glance at their potential use in the diagnostic and therapeutic decision-making process. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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Review
From Genetics to Histomolecular Characterization: An Insight into Colorectal Carcinogenesis in Lynch Syndrome
Int. J. Mol. Sci. 2021, 22(13), 6767; https://doi.org/10.3390/ijms22136767 - 23 Jun 2021
Viewed by 963
Abstract
Lynch syndrome is a hereditary cancer-predisposing syndrome caused by germline defects in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Carriers of pathogenic mutations in these genes have an increased lifetime risk of developing colorectal [...] Read more.
Lynch syndrome is a hereditary cancer-predisposing syndrome caused by germline defects in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. Carriers of pathogenic mutations in these genes have an increased lifetime risk of developing colorectal cancer (CRC) and other malignancies. Despite intensive surveillance, Lynch patients typically develop CRC after 10 years of follow-up, regardless of the screening interval. Recently, three different molecular models of colorectal carcinogenesis were identified in Lynch patients based on when MMR deficiency is acquired. In the first pathway, adenoma formation occurs in an MMR-proficient background, and carcinogenesis is characterized by APC and/or KRAS mutation and IGF2, NEUROG1, CDK2A, and/or CRABP1 hypermethylation. In the second pathway, deficiency in the MMR pathway is an early event arising in macroscopically normal gut surface before adenoma formation. In the third pathway, which is associated with mutations in CTNNB1 and/or TP53, the adenoma step is skipped, with fast and invasive tumor growth occurring in an MMR-deficient context. Here, we describe the association between molecular and histological features in these three routes of colorectal carcinogenesis in Lynch patients. The findings summarized in this review may guide the use of individualized surveillance guidelines based on a patient’s carcinogenesis subtype. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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Review
Molecular Alterations in Gastric Preneoplastic Lesions and Early Gastric Cancer
Int. J. Mol. Sci. 2021, 22(13), 6652; https://doi.org/10.3390/ijms22136652 - 22 Jun 2021
Viewed by 500
Abstract
Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) [...] Read more.
Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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Review
Molecular Alterations in Gastric Intestinal Metaplasia
Int. J. Mol. Sci. 2021, 22(11), 5758; https://doi.org/10.3390/ijms22115758 - 28 May 2021
Cited by 1 | Viewed by 889
Abstract
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers [...] Read more.
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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Review
Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations
Int. J. Mol. Sci. 2021, 22(9), 4388; https://doi.org/10.3390/ijms22094388 - 22 Apr 2021
Viewed by 635
Abstract
The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include [...] Read more.
The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions. Full article
(This article belongs to the Special Issue Molecular Alterations in GastroIntestinal Pre-invasive Lesions)
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