Elucidating immunological characteristics of the adenoma-carcinoma sequence in colorectal cancer patients in South Korea using a bioinformatics approach

• Published in: Scientific reports Vol. 14; no. 1; p. 10105
• Main Authors: Song, Jaeseung, Kim, Daeun, Jung, Junghyun, Choi, Eunyoung, Lee, Yubin, Jeong, Yeonbin, Lee, Byungjo, Lee, Sora, Shim, Yujeong, Won, Youngtae, Cho, Hyeki, Jang, Dong Kee, Kang, Hyoun Woo, Joo, Jong Wha J., Jang, Wonhee
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/553; 631/67/1504; 631/67/327; 631/67/69; Adenoma; Adenoma - genetics; Adenoma - immunology; Adenoma - pathology; Adenoma-carcinoma sequence; Advanced colorectal adenoma; Aged; Bioinformatics; Biomarkers, Tumor - genetics; Cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Computational Biology - methods; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Humanities and Social Sciences; Humans; Immune repertoire; Immunoglobulins; Immunology; Innate immunity; Kaplan-Meier Estimate; Lymphocytes B; Male; Malignancy; Middle Aged; multidisciplinary; Neoplasms; Prognosis; Recombination; Republic of Korea; Science; Science (multidisciplinary); Survival analysis; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors; Republic of Korea; South Korea; Immune repertoire; Colorectal cancer; Adenoma-carcinoma sequence; Advanced colorectal adenoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-56078-2

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.