Purpose: The aim of this study was to screen biomarkers specific to Lynch syndrome (LS) with colorectal cancer (CRC) or endometrial cancer (EC) to explore the mechanisms by which LS develops into CRC and EC and their differences.
Methods: Differentially expressed or differentially methylated genes and differential mutations were identified in 10 LS, 50 CRC, and 50 EC patients from TCGA, and genes overlapping between LS and CRC or EC (named SGs-LCs and SGs-LEs, respectively) were identified. Afterward, we annotated the enriched GO terms and pathways and constructed a protein-protein interaction (PPI) network. Finally, samples from 10 clinical cases with MSI-H/MSS CRC and EC were collected to verify the mutations and their correlations with five LS pathogenic genes in the SGs-LCs and SGs-LEs.
Results: A total of 494 SGs-LCs and 104 SGs-LEs were identified and enriched in 106 and 14 GO terms, respectively. There were great differences in the gene count and enriched terms between SGs-LCs and SGs-LEs. In the PPI network, SST, GCG, SNAP25, and NPY had the highest degree of connection among the SGs-LCs, and KIF20A and NUF2 had the highest degree of connection among the SGs-LE. In the SGs-LCs and SGs-LEs, the genes whose expression levels affected the survival of LS, CRC or EC patients were quite different.
Conclusions: COL11A1 was found to be mutated in MSS CRC patients, similar to the mutations of MSH6. SST, GCG, SNAP25, and NPY may be biomarkers for the development of LS into CRC, and KIF20A and NUF2 may be markers of LS developing into EC.
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http://dx.doi.org/10.1007/s10552-021-01543-w | DOI Listing |
Front Oncol
December 2024
Department of Integrative Translational Sciences, City of Hope, Beckman Research Institute, Duarte, CA, United States.
Over the past century, colorectal cancer (CRC) has become one of the most devastating cancers impacting the human population. To gain a deeper understanding of the molecular mechanisms driving this solid tumor, researchers have increasingly turned their attention to the tumor microenvironment (TME). Spatial transcriptomics and proteomics have emerged as a particularly powerful technology for deciphering the complexity of CRC tumors, given that the TME and its spatial organization are critical determinants of disease progression and treatment response.
View Article and Find Full Text PDFInnate Immun
December 2024
Department of Clinical Pathology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Background: Globally, colorectal cancer (CRC) is among the most prevalent malignant tumors. It is characterized by unlimited proliferation, invasion, and metastasis. MicroRNA-126 (miR-126) has been shown in many studies to play a significant role in CRC, but data regarding its role in CRC Egyptian patients are limited.
View Article and Find Full Text PDFJ Pathol
December 2024
Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland.
Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.
View Article and Find Full Text PDFJ Gastrointest Cancer
December 2024
Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, 518100, China.
Background And Objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis.
View Article and Find Full Text PDFLangenbecks Arch Surg
December 2024
Department of Surgery, TUM Universitätsklinikum Klinikum Rechts der Isar Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Objective: Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities (Haematologica 99:392-398, 2014; Dis Colon Rectum 51:213-217, 2008; Dis Esophagus 21:334-339, 2008). The impact of splenectomy in pancreatic cancer is not fully resolved (J Am Coll Surg 188:516-521, 1999; J Surg Oncol 119:784-793, 2019).
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