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Sci Rep ; 14(1): 10105, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698020

RESUMO

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.


Assuntos
Adenoma , Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Adenoma/genética , Adenoma/imunologia , Adenoma/patologia , República da Coreia , Biologia Computacional/métodos , Masculino , Feminino , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Estimativa de Kaplan-Meier , Perfilação da Expressão Gênica
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