A closer look at esophageal cancer through different lenses.

A closer look at esophageal cancer through different lenses.
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通过不同的镜头仔细观察食管癌。

DOI:
10.1016/j.ebiom.2021.103545
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发表时间:
2021-09
期刊:
影响因子:
11.1
通讯作者:
Lin DC
Lin DC
中科院分区:
医学1区
文献类型:
--
作者:
Lin DC

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食管鳞状细胞癌(ESCC)具有高度侵袭性和致死性,但与其他常见癌症相比,对其研究不足。对于ESCC患者来说,基因组引导疗法仍然是不可用的,这些患者的临床结果非常差,5年生存率低于20%。毫无疑问,迫切需要表征ESCC的生物学特性,以发现创新的治疗靶点和生物标志物。这不仅需要对大量患者进行表征(考虑到ESCC很强的肿瘤间异质性[2,3]),还需要深入了解整个肿瘤生态系统,这对癌症生物学和对治疗的反应性有很大影响。在这一期的《电子生物医学杂志》上,Li等人专门研究了这些问题,进行了广泛而深入的研究,并为理解ESCC中具有临床和转化价值的肿瘤内在和外在因素提供了新的见解。为了克服肿瘤间异质性并确定ESCC的共同改变,研究人员首先对来自多个已发表研究的718例ESCC患者样本的表达谱进行了综合分析,这是迄今为止最大的联合队列。共鉴定出112个常见差异表达基因。该基因列表为ESCC研究界提供了重要的资源,因为它们在不同的队列和平台上具有稳健性和可重复性。为了测试这些失调基因的功能必要性,作者使用来自DepMap数据库的全基因组CRISPR-Cas9功能缺失数据分析了ESCC细胞系的依赖谱。通过这种方法发现了许多新的候选功能,如heat1、TIMELESS、DTL、GINS1、RUVBL1和ECT2,它们值得未来的实验验证。此外,还提出了丰富的生物学途径。总之,这些结果可能反映了ESCC肿瘤在转录水平上最保守和最常见的改变。为了了解保守转录变化背后的表观遗传机制,我们对6个具有匹配RNA-的样本进行了ATAC-seq分析
Esophageal squamous cell carcinoma (ESCC) is highly aggressive and lethal, and yet it is understudied compared with other common cancers. Genome-guided therapies are still unavailable for ESCC patients, who suffer extremely poor clinical outcomes with a 5-year survival rate lower than 20%[1]. Undoubtedly, an urgent need exists to characterize the biology of ESCC for the discovery of innovative therapeutic targets and biomarkers. This requires not only characterization of a large number of patients (considering the strong intertumor heterogeneity of ESCC [2, 3]) but also in-depth understanding of the tumor ecosystem as a whole which strongly impacts cancer biology and responsiveness to treatment. In this issue of EBiomedicine [4], Li et al. have specifically taken on these issues, conducted investigations with significant breadth and depth, and provided novel insights into understanding both tumor-intrinsic and-extrinsic factors with clinical and translational values in ESCC. To overcome the inter-tumor heterogeneity and identify shared alterations in ESCC, the researchers first performed integrated analysis of expression profiling of 718 ESCC patient samples from multiple published studies, representing the largest combined cohort so far. A total of 112 common differentially expressed genes were identified. This list of genes provides an important resource for the ESCC research community, given their robustness and reproducibility across different cohorts and platforms. In order to test functional essentiality of these dysregulated genes, the authors analyzed the dependency profiles from ESCC cell lines using genome-wide CRISPR-Cas9 loss-of-function data from the DepMap database. A number of novel functional candidates were uncovered by this approach, such as HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2, which warrant future experimental validations. In addition, enriched biological pathways were presented. Together, these results likely reflect the most conserved and common alterations in ESCC tumors at the transcriptional level. As an attempt to understand epigenetic mechanisms underlying the conserved transcriptional changes, ATAC-seq was conducted on 6 samples with matched RNA-
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