{"title":"AURKA通过激活结直肠癌CD4+ T细胞增殖增强抗肿瘤免疫。","authors":"Yidong Xu, Wei Wang, Jiazi Yu, Jianpei Zhao, Xiaoyu Dai, Zhongchen Liu","doi":"10.1080/07357907.2025.2559403","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) ranks third globally in cancer incidence. Aurora Kinase A (AURKA) critically regulates tumor proliferation and microenvironment, yet its dual CRC roles remain unclear.</p><p><strong>Methods: </strong>We integrated bulk RNA-seq, scRNA-seq, and 10x Visium spatial transcriptomics to profile AURKA. Immune infiltration was assessed via CIBERSORT/ssGSEA. Clinical validation used IHC/HE staining. Immunotherapy associations were tested in ICB cohorts and murine models.</p><p><strong>Results: </strong>Pan-cancer analysis showed CRC-specific AURKA prognostic value (<i>p</i> < 0.05). High AURKA correlated with prolonged OS (median 68 vs 42 months; log-rank <i>P </i>= 0.034), conventional adenocarcinoma (<i>p</i> < 0.001), left-sided tumors (<i>p</i> < 0.001), and absent perineural invasion (<i>p</i> = 0.041). Pathway analyses linked AURKA to cell cycle (G2/M checkpoint) and immune pathways (IL-2/STAT5). Spatial transcriptomics identified peritumoral niches (clusters 6/7/12) co-expressing AURKA, CD4, MKI67, and immune-activation markers (HLA-DRB1, CXCL10). IHC confirmed AURKA-CD4 + T-cell correlation (R = 0.66, <i>p</i> < 0.05). scRNA-seq revealed AURKA dominance in proliferating T cells. High AURKA predicted anti-PD-1 response (HR = 0.44, <i>p</i> = 0.003) and CD4+ memory T-cell expansion in murine models.</p><p><strong>Conclusion: </strong>AURKA dually regulates tumor proliferation and immune engagement. Its spatial enrichment in T-cell niches supports its use as an immunotherapy biomarker.</p>","PeriodicalId":9463,"journal":{"name":"Cancer Investigation","volume":" ","pages":"1-18"},"PeriodicalIF":1.9000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"AURKA Enhances Antitumor Immunity by Activating CD4+ T Cell Proliferation in Colorectal Cancer.\",\"authors\":\"Yidong Xu, Wei Wang, Jiazi Yu, Jianpei Zhao, Xiaoyu Dai, Zhongchen Liu\",\"doi\":\"10.1080/07357907.2025.2559403\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Colorectal cancer (CRC) ranks third globally in cancer incidence. Aurora Kinase A (AURKA) critically regulates tumor proliferation and microenvironment, yet its dual CRC roles remain unclear.</p><p><strong>Methods: </strong>We integrated bulk RNA-seq, scRNA-seq, and 10x Visium spatial transcriptomics to profile AURKA. Immune infiltration was assessed via CIBERSORT/ssGSEA. Clinical validation used IHC/HE staining. Immunotherapy associations were tested in ICB cohorts and murine models.</p><p><strong>Results: </strong>Pan-cancer analysis showed CRC-specific AURKA prognostic value (<i>p</i> < 0.05). High AURKA correlated with prolonged OS (median 68 vs 42 months; log-rank <i>P </i>= 0.034), conventional adenocarcinoma (<i>p</i> < 0.001), left-sided tumors (<i>p</i> < 0.001), and absent perineural invasion (<i>p</i> = 0.041). Pathway analyses linked AURKA to cell cycle (G2/M checkpoint) and immune pathways (IL-2/STAT5). Spatial transcriptomics identified peritumoral niches (clusters 6/7/12) co-expressing AURKA, CD4, MKI67, and immune-activation markers (HLA-DRB1, CXCL10). IHC confirmed AURKA-CD4 + T-cell correlation (R = 0.66, <i>p</i> < 0.05). scRNA-seq revealed AURKA dominance in proliferating T cells. High AURKA predicted anti-PD-1 response (HR = 0.44, <i>p</i> = 0.003) and CD4+ memory T-cell expansion in murine models.</p><p><strong>Conclusion: </strong>AURKA dually regulates tumor proliferation and immune engagement. Its spatial enrichment in T-cell niches supports its use as an immunotherapy biomarker.</p>\",\"PeriodicalId\":9463,\"journal\":{\"name\":\"Cancer Investigation\",\"volume\":\" \",\"pages\":\"1-18\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-09-25\",\"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/10.1080/07357907.2025.2559403\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/07357907.2025.2559403","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
AURKA Enhances Antitumor Immunity by Activating CD4+ T Cell Proliferation in Colorectal Cancer.
Introduction: Colorectal cancer (CRC) ranks third globally in cancer incidence. Aurora Kinase A (AURKA) critically regulates tumor proliferation and microenvironment, yet its dual CRC roles remain unclear.
Methods: We integrated bulk RNA-seq, scRNA-seq, and 10x Visium spatial transcriptomics to profile AURKA. Immune infiltration was assessed via CIBERSORT/ssGSEA. Clinical validation used IHC/HE staining. Immunotherapy associations were tested in ICB cohorts and murine models.
Results: Pan-cancer analysis showed CRC-specific AURKA prognostic value (p < 0.05). High AURKA correlated with prolonged OS (median 68 vs 42 months; log-rank P = 0.034), conventional adenocarcinoma (p < 0.001), left-sided tumors (p < 0.001), and absent perineural invasion (p = 0.041). Pathway analyses linked AURKA to cell cycle (G2/M checkpoint) and immune pathways (IL-2/STAT5). Spatial transcriptomics identified peritumoral niches (clusters 6/7/12) co-expressing AURKA, CD4, MKI67, and immune-activation markers (HLA-DRB1, CXCL10). IHC confirmed AURKA-CD4 + T-cell correlation (R = 0.66, p < 0.05). scRNA-seq revealed AURKA dominance in proliferating T cells. High AURKA predicted anti-PD-1 response (HR = 0.44, p = 0.003) and CD4+ memory T-cell expansion in murine models.
Conclusion: AURKA dually regulates tumor proliferation and immune engagement. Its spatial enrichment in T-cell niches supports its use as an immunotherapy biomarker.
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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