Yan Wang, Jiawei Sun, Di Wang, Hongguang Liu, Qing Ma, Shuo Chen
{"title":"慢传输型便秘与结直肠癌的综合分析揭示其共同致病靶点及其潜在临床价值。","authors":"Yan Wang, Jiawei Sun, Di Wang, Hongguang Liu, Qing Ma, Shuo Chen","doi":"10.1080/07357907.2025.2506102","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Slow transit constipation (STC) is a potential risk of the onset of colorectal cancer (CRC). Thus, the purpose of this work is to focus on the co-pathogenic targets between STC and CRC, meanwhile evaluating their prognostic value for CRC.</p><p><strong>Methods: </strong>The miRNA and mRNA data of STC and CRC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The prognostic signature was constructed based on hub genes, which identified using differential expression analysis and LASSO Cox regression analysis. The hub genes were validated employing multiple public databases. Enrichment analysis was employed to elucidate their functions. Survival analysis was performed using Kaplan-Meier method. Transcription factor binding sites were predicted and verified using FIMO and ChIP-seq database, respectively.</p><p><strong>Results: </strong>We identified four common key differentially expressed miRNAs of STC and CRC, including hsa-miR-340, hsa-miR-30b, hsa-miR-20b, and hsa-miR-29c (p-value <0.05), and their targets were involved in the CRC's metabolic processes (all p-values <0.05). We developed a prognostic signature based on nine hub genes, and patient prognosis could be predicted employing Risk score = 0.099063054* <i>NOG</i> + 0.074815408* <i>PLD5</i> + 0.003499667* <i>NOVA1</i> + 0.051762032*<i>DTNA</i> + 0.050495722* <i>GPR26</i> + 0.045057094* <i>TNFAIP8L3</i> + 0.097209257* <i>SLC29A4</i>+ (-0.246941474)* <i>CCNJL</i> + 0.039294168* <i>TRABD2B</i>. High-risk patients exhibited significantly poorer prognosis (p-value <0.05). The hub genes <i>CCNJL</i>, <i>NOVA1</i>, <i>PLD5</i>, and <i>SLC29A4</i> were significantly down-regulated targets of hsa-miR-340 in the CRC samples (p-value <0.05). Functional analyses suggested their involvement in immune-related processes (all p-values <0.05). Our exploration of upstream regulators revealed six and one reliable transcription factors for <i>CCNJL</i> and <i>SLC29A4</i>, respectively.</p><p><strong>Conclusion: </strong>This study delved into common biomarkers between STC and CRC, and developed a reliable prognostic signature for CRC.</p>","PeriodicalId":9463,"journal":{"name":"Cancer Investigation","volume":" ","pages":"337-354"},"PeriodicalIF":1.9000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Integrated Analysis of Slow Transit Constipation and Colorectal Cancer Reveals the Co-Pathogenic Targets and Their Potential Clinical Value.\",\"authors\":\"Yan Wang, Jiawei Sun, Di Wang, Hongguang Liu, Qing Ma, Shuo Chen\",\"doi\":\"10.1080/07357907.2025.2506102\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Slow transit constipation (STC) is a potential risk of the onset of colorectal cancer (CRC). Thus, the purpose of this work is to focus on the co-pathogenic targets between STC and CRC, meanwhile evaluating their prognostic value for CRC.</p><p><strong>Methods: </strong>The miRNA and mRNA data of STC and CRC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The prognostic signature was constructed based on hub genes, which identified using differential expression analysis and LASSO Cox regression analysis. The hub genes were validated employing multiple public databases. Enrichment analysis was employed to elucidate their functions. Survival analysis was performed using Kaplan-Meier method. Transcription factor binding sites were predicted and verified using FIMO and ChIP-seq database, respectively.</p><p><strong>Results: </strong>We identified four common key differentially expressed miRNAs of STC and CRC, including hsa-miR-340, hsa-miR-30b, hsa-miR-20b, and hsa-miR-29c (p-value <0.05), and their targets were involved in the CRC's metabolic processes (all p-values <0.05). We developed a prognostic signature based on nine hub genes, and patient prognosis could be predicted employing Risk score = 0.099063054* <i>NOG</i> + 0.074815408* <i>PLD5</i> + 0.003499667* <i>NOVA1</i> + 0.051762032*<i>DTNA</i> + 0.050495722* <i>GPR26</i> + 0.045057094* <i>TNFAIP8L3</i> + 0.097209257* <i>SLC29A4</i>+ (-0.246941474)* <i>CCNJL</i> + 0.039294168* <i>TRABD2B</i>. High-risk patients exhibited significantly poorer prognosis (p-value <0.05). The hub genes <i>CCNJL</i>, <i>NOVA1</i>, <i>PLD5</i>, and <i>SLC29A4</i> were significantly down-regulated targets of hsa-miR-340 in the CRC samples (p-value <0.05). Functional analyses suggested their involvement in immune-related processes (all p-values <0.05). Our exploration of upstream regulators revealed six and one reliable transcription factors for <i>CCNJL</i> and <i>SLC29A4</i>, respectively.</p><p><strong>Conclusion: </strong>This study delved into common biomarkers between STC and CRC, and developed a reliable prognostic signature for CRC.</p>\",\"PeriodicalId\":9463,\"journal\":{\"name\":\"Cancer Investigation\",\"volume\":\" \",\"pages\":\"337-354\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/07357907.2025.2506102\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/07357907.2025.2506102","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/2 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Integrated Analysis of Slow Transit Constipation and Colorectal Cancer Reveals the Co-Pathogenic Targets and Their Potential Clinical Value.
Background: Slow transit constipation (STC) is a potential risk of the onset of colorectal cancer (CRC). Thus, the purpose of this work is to focus on the co-pathogenic targets between STC and CRC, meanwhile evaluating their prognostic value for CRC.
Methods: The miRNA and mRNA data of STC and CRC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The prognostic signature was constructed based on hub genes, which identified using differential expression analysis and LASSO Cox regression analysis. The hub genes were validated employing multiple public databases. Enrichment analysis was employed to elucidate their functions. Survival analysis was performed using Kaplan-Meier method. Transcription factor binding sites were predicted and verified using FIMO and ChIP-seq database, respectively.
Results: We identified four common key differentially expressed miRNAs of STC and CRC, including hsa-miR-340, hsa-miR-30b, hsa-miR-20b, and hsa-miR-29c (p-value <0.05), and their targets were involved in the CRC's metabolic processes (all p-values <0.05). We developed a prognostic signature based on nine hub genes, and patient prognosis could be predicted employing Risk score = 0.099063054* NOG + 0.074815408* PLD5 + 0.003499667* NOVA1 + 0.051762032*DTNA + 0.050495722* GPR26 + 0.045057094* TNFAIP8L3 + 0.097209257* SLC29A4+ (-0.246941474)* CCNJL + 0.039294168* TRABD2B. High-risk patients exhibited significantly poorer prognosis (p-value <0.05). The hub genes CCNJL, NOVA1, PLD5, and SLC29A4 were significantly down-regulated targets of hsa-miR-340 in the CRC samples (p-value <0.05). Functional analyses suggested their involvement in immune-related processes (all p-values <0.05). Our exploration of upstream regulators revealed six and one reliable transcription factors for CCNJL and SLC29A4, respectively.
Conclusion: This study delved into common biomarkers between STC and CRC, and developed a reliable prognostic signature for CRC.
期刊介绍：
Cancer Investigation is one of the most highly regarded and recognized journals in the field of basic and clinical oncology. It is designed to give physicians a comprehensive resource on the current state of progress in the cancer field as well as a broad background of reliable information necessary for effective decision making. In addition to presenting original papers of fundamental significance, it also publishes reviews, essays, specialized presentations of controversies, considerations of new technologies and their applications to specific laboratory problems, discussions of public issues, miniseries on major topics, new and experimental drugs and therapies, and an innovative letters to the editor section. One of the unique features of the journal is its departmentalized editorial sections reporting on more than 30 subject categories covering the broad spectrum of specialized areas that together comprise the field of oncology. Edited by leading physicians and research scientists, these sections make Cancer Investigation the prime resource for clinicians seeking to make sense of the sometimes-overwhelming amount of information available throughout the field. In addition to its peer-reviewed clinical research, the journal also features translational studies that bridge the gap between the laboratory and the clinic.
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