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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2020)

Objective: Determine the clinical effectiveness of definitive treatment for non-small cell lung cancer (NSCLC) and perform a comparative effectiveness study of the different techniques, between surgical resection of lobectomy, radiation therapy (RT), and stereotactic body radiation (SBRT).

Patients and Methods: This study used data from the SEER Program, with 20,889 patients with Stage IA to IIIC. NSCLC The inclusion criteria were any patient identified from SEER from 2014 to 2016, over 18 years old.

Chi-squared tests were used to evaluate the differences in dichotomous variables between the treatment groups. Unadjusted Kaplan-Meier methods were used to estimate overall survival and cancer-specific survival, and we used log-rank tests to evaluate the differences in time-to-event outcomes. Two-sided p values were used, and significance level was set at 0.05. Adjusted Cox regression models assumed proportional hazards.

Results: A total of 13,760 NSCLC patients with clinical stage IA to IIIC treated with lobectomy were compared with 7,129 patients treated with radiotherapy. Adjusted multivariable Cox proportional hazards models found lobectomy to be associated with significantly better outcomes compared to radiotherapy for both early-stage (hazard ratio, T1N0, 0.31, P<.001) and advanced-stage (hazard ratio, T2N2, 0.43, P<.001). Additionally, patients undergoing lobectomy had improved mean cancer-specific survival for stages IA to IIIC.

Conclusion: Among NSCLC patients with clinical stage IA to IIIC in the SEER Database, surgical resection with lobectomy is associated with significantly improved outcomes compared to definitive radiation. Radiation for early stage disease (SBRT) or combined with chemotherapy for locally advanced-stage disease remains a good treatment option. However, when medical comorbidities and tumor characteristics permit, surgical resection should be pursued. For patients with unresectable disease, this study supports the consideration of chemoradiation as a tool to enable downstaging to achieve surgical resection.

    Cover page: Surgical and Non-Surgical Outcomes for Patients with Non-Small Cell Lung Cancer
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2023)
    Natural sequence variation within mitochondrial DNA (mtDNA) contributes to human phenotypes and may serve as natural genetic markers in human cells for clonal and lineage tracing. We recently developed a single-cell multi-omic approach, called mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (mtscATAC-seq), enabling concomitant high-throughput mtDNA genotyping and accessible chromatin profiling. Specifically, our technique allows the mitochondrial genome-wide inference of mtDNA variant heteroplasmy along with information on cell state and accessible chromatin variation in individual cells. Leveraging somatic mtDNA mutations, our method further enables inference of clonal relationships among native ex vivo-derived human cells not amenable to genetic engineering-based clonal tracing approaches. Here, we provide a step-by-step protocol for the use of mtscATAC-seq, including various cell-processing and flow cytometry workflows, by using primary hematopoietic cells, subsequent single-cell genomic library preparation and sequencing that collectively take ~3-4 days to complete. We discuss experimental and computational data quality control metrics and considerations for the extension to other mammalian tissues. Overall, mtscATAC-seq provides a broadly applicable platform to map clonal relationships between cells in human tissues, investigate fundamental aspects of mitochondrial genetics and enable additional modes of multi-omic discovery.
      Cover page: Mitochondrial single-cell ATAC-seq for high-throughput multi-omic detection of mitochondrial genotypes and chromatin accessibility.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2021)
      The autoimmune regulator (Aire), a well-defined transcriptional regulator in the thymus, is also found in extrathymic Aire-expressing cells (eTACs) in the secondary lymphoid organs. eTACs are hematopoietic antigen-presenting cells and inducers of immune tolerance, but their precise identity has remained unclear. Here, we use single-cell multiomics, transgenic murine models, and functional approaches to define eTACs at the transcriptional, genomic, and proteomic level. We find that eTACs consist of two similar cell types: CCR7+ Aire-expressing migratory dendritic cells (AmDCs) and an Airehi population coexpressing Aire and retinoic acid receptor–related orphan receptor γt (RORγt) that we term Janus cells (JCs). Both JCs and AmDCs have the highest transcriptional and genomic homology to CCR7+ migratory dendritic cells. eTACs, particularly JCs, have highly accessible chromatin and broad gene expression, including a range of tissue-specific antigens, as well as remarkable homology to medullary thymic epithelium and RANK-dependent Aire expression. Transgenic self-antigen expression by eTACs is sufficient to induce negative selection and prevent autoimmune diabetes. This transcriptional, genomic, and functional symmetry between eTACs (both JCs and AmDCs) and medullary thymic epithelium—the other principal Aire-expressing population and a key regulator of central tolerance—identifies a core program that may influence self-representation and tolerance across the spectrum of immune development.
        Cover page: Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium
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