A closer look at esophageal cancer through different lenses.
A closer look at esophageal cancer through different lenses.
复制标题
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
中科院分区:
文献类型:
--
作者:
Lin DC
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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