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Quantitative imaging-based analysis of cell state heterogeneity in Head and Neck Squamous Cell Carcinoma (HNSCC)

Show simple item record 2021-06-30T05:38:58Z 2021-06-30
dc.title Quantitative imaging-based analysis of cell state heterogeneity in Head and Neck Squamous Cell Carcinoma (HNSCC) en
ethesis.faculty Bio- ja ympäristötieteellinen tiedekunta fi
ethesis.faculty Faculty of Biological and Environmental Sciences en
ethesis.faculty Bio- och miljövetenskapliga fakulteten sv
ethesis.faculty.URI Helsingin yliopisto fi University of Helsinki en Helsingfors universitet sv
dct.creator Dawka, Sagarika
dct.issued 2021
dct.language.ISO639-2 eng
dct.abstract Head and neck squamous cell carcinoma (HNSCC) is a diverse group of cancers defined by their localization in the head and neck region. These cancers are recognized for the heterogeneity between tumors from separate patients (inter-patient heterogeneity) as well as between cell types within individual tumors (intra-tumoral heterogeneity). Heterogeneity poses a major clinical challenge by making accurate diagnosis and selection of treatment options difficult. This study aims to improve precision of prognosis, quantify heterogeneity in HNSCC, and address its functional implications using two approaches: (1) profiling a set of HNSCC patient tumors using multiplexed immunohistochemistry and single-cell computational methods to identify a set of phenotypic descriptors correlating with differences in survival; and (2) using patient-derived cancer cell lines to investigate which cellular features correlate with relevant functional properties such as plasticity, invasiveness, clonogenicity and tumorsphere-forming abilities of cells. Epithelial-mesenchymal transition (EMT) as well as excistence of stem cell like states have been implicated in cancer aggressiveness and poor outcomes. We thus focused on identification of putative EMT, partial EMT (pEMT) and stem cell-like states. Based on a combination of morphometric analyses and stem cell- and EMT marker profiling, our computational method assigned patients into groups with different survival probabilities, and these patients’ tumors were found to differ in their expression of the stem cell transcription factor Sox2, the EMT transcription factor Slug, and in their morphometric parameters. Functional studies of patient-derived cell lines found that significant differences exist in protein expression, morphological features and cell behaviours between cell lines in vitro, and that inhibiting EMT promotes clonogenicity and can increase Sox2 expression. Thus, this study highlights important heterogeneous patient phenotypes and cellular behaviours in HNSCC, and implicates the need for a multimodal approach to diagnosis and therapy of this cancer. en
dct.subject head and neck squamous cell carcinoma (HNSCC) en
dct.subject head and neck cancer en
dct.subject tumour heterogeneity en
dct.subject epithelial-mesenchymal transition (EMT) en
dct.subject partial EMT (pEMT) en
dct.subject nuclear mechanics en
dct.language en
ethesis.language englanti fi
ethesis.language English en
ethesis.language engelska sv
ethesis.supervisor Wickstrom, Sara
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
ethesis.thesistype pro gradu-avhandlingar sv
dct.identifier.ethesis E-thesisID:58025ad5-e826-4ea0-b9f5-e3869f610554 2024-06-30
ethesis-internal.timestamp.reviewStep 2021-05-10 07:45:35:015
ethesis.principalprofessor Heino, Tapio
dct.identifier.urn URN:NBN:fi:hulib-202106303264
dc.type.dcmitype Text
ethesis.facultystudyline Solu- ja kehitysbiologia fi
ethesis.facultystudyline Cell and Developmental Biology en
ethesis.facultystudyline Cell- och utvecklingsbiologi sv
ethesis.mastersdegreeprogram Genetiikan ja molekulaaristen biotieteiden maisteriohjelma fi
ethesis.mastersdegreeprogram Master's Programme in Genetics and Molecular Biosciences en
ethesis.mastersdegreeprogram Magisterprogrammet i genetik och molekylära biovetenskaper sv

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