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| Status |
Public on Nov 11, 2022 |
| Title |
Widespread genomic/molecular alterations of DNA helicases and their clinical/therapeutic implications across human cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
DNA helicases are essential to genomic stability by regulating DNA metabolisms and their loss-of-function mutations lead to genomic instability and predisposition to cancer. Paradoxically, overexpression of DNA helicases is observed in several cancers, but systemic analyses of their alterations and biological or clinical implications in human cancer have not been reported. Here we analyzed genomic and molecular alterations in 12 important DNA helicases across 33 cancer types from the TCGA dataset to provide an overview of their aberrations. Significant expression heterogeneity of 12 DNA helicases was observed. We calculated DNA helicase score (DHS) based on their expression, and categorized tumors into high, low and intermediate subtypes. High DHS subtypes were robustly associated with stemness, proliferation, hyperactivated oncogenic signaling, longer telomeres, total mutation burden, copy number alterations (CNAs) and shorter survival. Importantly, tumors with high DHSs exhibited stronger expression of alternative end-join (alt-EJ) factors, indicative of sensitivity to chemo- and radio-therapies. Several drugs are identified to inhibit DNA helicases, with the Auror A kinase inhibitor Danusertib as the strongest candidate. The aberrant expression of DNA helicases was associated with CNAs, DNA methylation and m6A regulators. Our findings thus reveal widespread dysregulation of DNA helicases and their broad connection with featured oncogenic aberrations across human cancer. The close association of DHS with the alt-EJ pathway and cellular proliferation suggests that tumors with higher DHS are sensitive to chemotherapy and radiotherapy; The Auror A kinase inhibitor Danusertib may also inhibit DNA helicases. These findings thus contribute to DNA helicase-based cancer therapy.
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| Overall design |
mRNA expression profile in 10 pairs of clear cell renal cell carcinoma tissues and adjacent non-neoplastic tissues.
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| Web link |
https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(22)01582-7
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| Contributor(s) |
Qin X, Wang J, Wang X, Huang T, Fang Z, Yan L, Fan Y, Xu D |
| Citation(s) |
36586240, 37197417, 37434223 |
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| Submission date |
Nov 06, 2022 |
| Last update date |
Sep 12, 2023 |
| Contact name |
Xin Qin |
| Organization name |
Qilu hospital of Shandong University
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| Street address |
Wenhuaxi Road
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| City |
jinan |
| State/province |
Shandong Province |
| ZIP/Postal code |
265600 |
| Country |
China |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (20)
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| GSM6716400 |
clear cell renal cell carcinoma sample 1CA |
| GSM6716401 |
clear cell renal cell carcinoma sample 2CA |
| GSM6716402 |
clear cell renal cell carcinoma sample 3CA |
| GSM6716403 |
clear cell renal cell carcinoma sample 4CA |
| GSM6716404 |
clear cell renal cell carcinoma sample 5CA |
| GSM6716405 |
clear cell renal cell carcinoma sample 6CA |
| GSM6716406 |
clear cell renal cell carcinoma sample 7CA |
| GSM6716407 |
clear cell renal cell carcinoma sample 8CA |
| GSM6716408 |
clear cell renal cell carcinoma sample 9CA |
| GSM6716409 |
clear cell renal cell carcinoma sample 10CA |
| GSM6716410 |
adjacent non-neoplastic tissue sample 1NT |
| GSM6716411 |
adjacent non-neoplastic tissue sample 2NT |
| GSM6716412 |
adjacent non-neoplastic tissue sample 3NT |
| GSM6716413 |
adjacent non-neoplastic tissue sample 4NT |
| GSM6716414 |
adjacent non-neoplastic tissue sample 5NT |
| GSM6716415 |
adjacent non-neoplastic tissue sample 6NT |
| GSM6716416 |
adjacent non-neoplastic tissue sample 7NT |
| GSM6716417 |
adjacent non-neoplastic tissue sample 8NT |
| GSM6716418 |
adjacent non-neoplastic tissue sample 9NT |
| GSM6716419 |
adjacent non-neoplastic tissue sample 10NT |
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| Relations |
| BioProject |
PRJNA898782 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE217386_Count.allSamples.txt.gz |
4.5 Mb |
(ftp)(http) |
TXT |
| GSE217386_FPKM.allSamples.txt.gz |
5.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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