Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
ABSTRACT Objective The response to neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer (LARC) varies from achieving a complete pathological response to encountering resistance to treatment. Therefore, biomarkers for predicting the NACRT responses should be identified. This prosp...
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2025-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70815 |
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| author | Xi Zhu Xiaoming Kao Leilei Liu Xuan Wang Yang Li Qiurong Li |
| author_facet | Xi Zhu Xiaoming Kao Leilei Liu Xuan Wang Yang Li Qiurong Li |
| author_sort | Xi Zhu |
| collection | DOAJ |
| description | ABSTRACT Objective The response to neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer (LARC) varies from achieving a complete pathological response to encountering resistance to treatment. Therefore, biomarkers for predicting the NACRT responses should be identified. This prospective study aimed to identify key genomic biomarkers as the predictors of the NACRT response with LARC. Methods Overall, 67 patients with LARC treated with NACRT and proctectomy were divided into two groups based on the tumor regression grade (TRG) for identifying key biomarkers. Patients with a TRG of 0 or 1 were assigned to the sensitive response group, and patients with a TRG of 2 or 3 were the resistant response group. Twenty‐nine postsurgical tumor samples were collected for whole exome sequencing (WES) to identify genomic variation biomarkers. The other 38 pairs of tumor specimens from pretreatment and postsurgery samples were evaluated by immunohistochemistry (IHC) to examine the biomarker features. Results In the WES subcohort, 11 genes showed copy number variation, including FNKBIA, ARID1A, CCND2, CDK4, LYN, MDM2, RAD51B, RARA, SPEN, STAT3, and Daxx, which has the highest copy number variation. For the IHC subcohort, Daxx was initially highly expressed in the nuclei of tumor cells, particularly in the sensitive response group, while varying its expression after NACRT, demonstrating that Daxx levels were related to treatment responses and the survival benefit, especially a better disease‐free survival (DFS). Conclusion We identified multiple genomic variations between sensitive and resistant responders and verified that Daxx is a potential predictive biomarker of the response to NACRT in LARC. |
| format | Article |
| id | doaj-art-c1f5ddf29d1c4b86b738c42bec8181bd |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-c1f5ddf29d1c4b86b738c42bec8181bd2025-08-20T03:10:39ZengWileyCancer Medicine2045-76342025-03-01146n/an/a10.1002/cam4.70815Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal CancerXi Zhu0Xiaoming Kao1Leilei Liu2Xuan Wang3Yang Li4Qiurong Li5Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing ChinaResearch Institute of General Surgery, Jinling Hospital Nanjing Medical University Nanjing ChinaDepartment of Pathology, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing ChinaDepartment of Pathology, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing ChinaResearch Institute of General Surgery, Jinling Hospital Nanjing Medical University Nanjing ChinaResearch Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing ChinaABSTRACT Objective The response to neoadjuvant chemoradiotherapy (NACRT) for locally advanced rectal cancer (LARC) varies from achieving a complete pathological response to encountering resistance to treatment. Therefore, biomarkers for predicting the NACRT responses should be identified. This prospective study aimed to identify key genomic biomarkers as the predictors of the NACRT response with LARC. Methods Overall, 67 patients with LARC treated with NACRT and proctectomy were divided into two groups based on the tumor regression grade (TRG) for identifying key biomarkers. Patients with a TRG of 0 or 1 were assigned to the sensitive response group, and patients with a TRG of 2 or 3 were the resistant response group. Twenty‐nine postsurgical tumor samples were collected for whole exome sequencing (WES) to identify genomic variation biomarkers. The other 38 pairs of tumor specimens from pretreatment and postsurgery samples were evaluated by immunohistochemistry (IHC) to examine the biomarker features. Results In the WES subcohort, 11 genes showed copy number variation, including FNKBIA, ARID1A, CCND2, CDK4, LYN, MDM2, RAD51B, RARA, SPEN, STAT3, and Daxx, which has the highest copy number variation. For the IHC subcohort, Daxx was initially highly expressed in the nuclei of tumor cells, particularly in the sensitive response group, while varying its expression after NACRT, demonstrating that Daxx levels were related to treatment responses and the survival benefit, especially a better disease‐free survival (DFS). Conclusion We identified multiple genomic variations between sensitive and resistant responders and verified that Daxx is a potential predictive biomarker of the response to NACRT in LARC.https://doi.org/10.1002/cam4.70815Daxxlocally advanced rectal cancerneoadjuvant chemoradiotherapypredictive biomarkertherapeutic response |
| spellingShingle | Xi Zhu Xiaoming Kao Leilei Liu Xuan Wang Yang Li Qiurong Li Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Cancer Medicine Daxx locally advanced rectal cancer neoadjuvant chemoradiotherapy predictive biomarker therapeutic response |
| title | Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_full | Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_fullStr | Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_full_unstemmed | Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_short | Daxx Variation as a Potential Predictive Marker of the Therapeutic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_sort | daxx variation as a potential predictive marker of the therapeutic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer |
| topic | Daxx locally advanced rectal cancer neoadjuvant chemoradiotherapy predictive biomarker therapeutic response |
| url | https://doi.org/10.1002/cam4.70815 |
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