ST6GAL1 与直肠癌化疗反应差有关

IF 4.8 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Mary Smithson , Sameer Al Diffalha , Regina K. Irwin , Gregory Williams , M. Chandler McLeod , Vivek Somasundaram , Susan L. Bellis , Karin M. Hardiman
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引用次数: 0

摘要

导言:大肠癌是第三大常见癌症死因。直肠癌占所有结直肠癌病例的三分之一。局部晚期直肠癌的治疗包括化疗和手术。我们以前曾发现 ST6GAL1 是体外化疗耐药的原因之一,并假设它与人类衍生模型和人体组织的不良反应相关。化疗后通过免疫染色法评估 ST6GAL1 和裂解 Caspase-3 (CC3)。本研究机构从接受化疗的 26 例直肠腺癌患者的治疗前和治疗后标本中创建了组织微阵列(TMA)。对 ST6GAL1 进行了免疫组化,评估了癌细胞染色阳性率,并测量了与病理反应等级的相关性。结果类器官模型接受化疗后,ST6GAL1 mRNA 和蛋白均显著增加。以 ST6GAL1 敲除为靶点的类器官模型在治疗后发现 CC3 增加。在组织芯片中,42%的患者样本在治疗后ST6GAL1的肿瘤细胞染色百分比增加。结论ST6GAL1与人类直肠癌的耐药性有关,在类器官模型中敲除ST6GAL1可减轻化疗引起的细胞凋亡耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ST6GAL1 is associated with poor response to chemoradiation in rectal cancer

Introduction

Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues.

Methods

Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured.

Results

Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01).

Conclusion

ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.

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来源期刊
Neoplasia
Neoplasia 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
82
审稿时长
26 days
期刊介绍: Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.
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