Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells.
Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells.
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DOI：
10.1186/s12967-023-04260-x
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发表时间：
2023-06-16
影响因子：
7.4
通讯作者：
Huang, Qian
中科院分区：
文献类型：
--
作者：
Song, Yanwei;Deng, Zheng;Sun, Haoran;Zhao, Yucui;Zhao, Ruyi;Cheng, Jin;Huang, Qian
具有放射抵抗能力的肿瘤细胞在放射治疗后可以逃脱细胞死亡的命运，成为治疗失败的主要原因。放疗后肿瘤的再增殖主要是这组残留细胞，这大大降低了复发肿瘤对治疗的敏感性，导致临床结局不佳。因此，揭示放射抵抗细胞参与肿瘤再增殖的机制，对于肿瘤患者获得更好的预后具有重要意义。通过使用辐射抗性细胞（来自GEO数据库）和TCGA结直肠癌的遗传数据来搜索共表达基因。单因素和多因素考克斯回归分析确定最显著的共表达基因，以建立预后指标。Logistic分析、WGCNA分析和其他类型的肿瘤被纳入以验证该指标的预测能力。RT-qPCR检测大肠癌细胞系中关键基因的表达水平。克隆形成实验检测关键基因敲减细胞的辐射敏感性和再增殖能力。建立了基于TCGA结直肠癌患者的预后指标，该指标包含四个关键的辐射抗性基因（LGR 5，KCNN 4，TNS 4，CENPH）。该指标被证明与接受放射治疗的结直肠癌患者的预后显著相关，并且在其他五种癌症中也具有可接受的预测效果。RT-qPCR显示关键基因的表达水平与大肠癌细胞的辐射抗性水平基本一致。与对照组相比，所有关键基因敲除细胞的克隆形成能力在辐射处理后均下降。提示LGR 5、KCNN 4、TNS 4和CENPH与大肠癌细胞的放射敏感性相关，它们组成的指标可以反映大肠癌放射治疗患者的预后。我们的数据提供了参与肿瘤再增殖的放射抗性肿瘤细胞的证据，并为接受放射治疗的患者提供了关于肿瘤进展的认可预后指标。在线版本包含补充材料，可通过10.1186/s12967-023-04260-x获得。
Tumor cells with the capability of radiation resistance can escape the fate of cell death after radiotherapy, serving as the main cause of treatment failure. Repopulation of tumors after radiotherapy is dominated by this group of residual cells, which greatly reduce the sensitivity of recurrent tumors to the therapy, resulting in poor clinical outcomes. Therefore, revealing the mechanism of radiation resistant cells participating in tumor repopulation is of vital importance for cancer patients to obtain a better prognosis. Co-expressed genes were searched by using genetic data of radiation resistant cells (from GEO database) and TCGA colorectal cancer. Univariate and multivariate Cox regression analysis were performed to define the most significant co-expressed genes for establishing prognostic indicator. Logistic analysis, WGCNA analysis, and other types of tumors were included to verify the predictive ability of the indicator. RT-qPCR was carried out to test expression level of key genes in colorectal cancer cell lines. Colongenic assay was utilized to test the radio-sensitivity and repopulation ability of key gene knockdown cells. Prognostic indicator based on TCGA colorectal cancer patients containing four key radiation resistance genes (LGR5, KCNN4, TNS4, CENPH) was established. The indicator was shown to be significantly correlated with the prognosis of colorectal cancer patients undergoing radiotherapy, and also had an acceptable predictive effect in the other five types of cancer. RT-qPCR showed that expression level of key genes was basically consistent with the radiation resistance level of colorectal cancer cells. The clonogenic ability of all key gene knockdown cells decreased after radiation treatment compared with the control groups. Our data suggest that LGR5, KCNN4, TNS4 and CENPH are correlated with radiation sensitivity of colorectal cancer cells, and the indicator composed by them can reflect the prognosis of colorectal cancer patients undergoing radiation therapy. Our data provide an evidence of radiation resistant tumor cells involved in tumor repopulation, and give patients undergoing radiotherapy an approving prognostic indicator with regard to tumor progression. The online version contains supplementary material available at 10.1186/s12967-023-04260-x.
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
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DOI：
10.1016/j.bbrc.2017.10.072
发表时间：
2017-12-09
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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影响因子：
3.8
作者：
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通讯作者：
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影响因子：
2.4
作者：
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