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The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes.
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Internal Motion Estimation by Internal-external Motion Modeling for Lung Cancer Radiotherapy
The aim of this study is to develop an internal-external correlation model for internal motion estimation for lung cancer radiotherapy. Deformation vector fields that characterize the internal-external motion are obtained by respectively registering the internal organ meshes and external surface meshes from the 4DCT images via a recently developed local topology preserved non-rigid point matching algorithm. A composite matrix is constructed by combing the estimated internal phasic DVFs with external phasic and directional DVFs. Principle component analysis is then applied to the composite matrix to extract principal motion characteristics, and generate model parameters to correlate the internal-external motion. The proposed model is evaluated on a 4D NURBS-based cardiac-torso (NCAT) synthetic phantom and 4DCT images from five lung cancer patients. For tumor tracking, the center of mass errors of the tracked tumor are 0.8(±0.5)mm/0.8(±0.4)mm for synthetic data, and 1.3(±1.0) mm/1.2(±1.2)mm for patient data in the intra-fraction/inter-fraction tracking, respectively. For lung tracking, the percent errors of the tracked contours are 0.06(±0.02)/0.07(±0.03) for synthetic data, and 0.06(±0.02)/0.06(±0.02) for patient data in the intra-fraction/inter-fraction tracking, respectively. The extensive validations have demonstrated the effectiveness and reliability of the proposed model in motion tracking for both the tumor and the lung in lung cancer radiotherapy.
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- Award ID(s):
- 1657364
- PAR ID:
- 10058440
- Date Published:
- Journal Name:
- Scientific reports
- Volume:
- 8
- ISSN:
- 2045-2322
- Page Range / eLocation ID:
- Article number: 3677
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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