关键词: Colorectal cancer DNA damage repair ZNF281 prognosis radioresistance

Mesh : Humans Animals Mice Rectal Neoplasms / genetics radiotherapy drug therapy Prognosis Chemoradiotherapy Neoadjuvant Therapy Retrospective Studies Treatment Outcome Repressor Proteins / therapeutic use

来  源:   DOI:10.1080/07853890.2023.2278619   PDF(Pubmed)

Abstract:
The treatment of Colorectal cancer (CRC) is extremely complex and survival rates vary depending on the stage of the disease at the time of diagnosis. Neoadjuvant chemoradiotherapy (NACRT), is the conventional treatment for locally advanced rectal cancer (LARC); however, the resistance to chemoradiotherapy in LARC is difficult to predict.
In this study, clinical data of 126 LARC patients were collected and analyzed, and relevant validation was performed using GEO database and in vitro and in vivo experiments, including Western blotting and Real-time quantitative PCR, immunohistochemistry, immunofluorescence, clonogenic cell survival assays, and nude-mouse xenograft models.
In patients with LARC who were treated with neoadjuvant radiotherapy (NART), higher ZNF281 expression in malignant tissue was associated with a poorer prognosis and lesser degree of tumor regression. Cell and mouse experiments have shown that ZNF281 reduces the damage caused by X-rays to CRC cells and tumors grown in mice.
We found that the expression of ZNF281 predicted the radiation response of CRC cells and suggested the prognosis of patients with LARC who received neoadjuvant radiation therapy.
摘要:
结直肠癌(CRC)的治疗是极其复杂的,并且存活率根据诊断时的疾病阶段而变化。新辅助放化疗(NACRT),是局部晚期直肠癌(LARC)的常规治疗方法;然而,LARC对放化疗的耐药性难以预测.
在这项研究中,收集和分析126例LARC患者的临床资料,并使用GEO数据库和体外和体内实验进行相关验证,包括Western印迹和实时定量PCR,免疫组织化学,免疫荧光,克隆细胞存活测定,和裸鼠异种移植模型。
在接受新辅助放疗(NART)治疗的LARC患者中,恶性组织中ZNF281的高表达与预后较差和肿瘤消退程度较低相关.细胞和小鼠实验表明,ZNF281减少了X射线对小鼠中生长的CRC细胞和肿瘤的损伤。
我们发现ZNF281的表达可预测CRC细胞的放射反应,并提示接受新辅助放射治疗的LARC患者的预后。
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