UBC Theses and Dissertations
Identifying putative biomarkers for lymph node metastasis in oral cancer Liu, Kelly Yi Ping
Oral cancer metastasis to cervical lymph nodes (LN+) has been one of the major indicators of poor prognosis, which has not been improved over the past five decades. There remains a need for improved biomarkers for risk assessment. Pathology of primary tumours has been commonly used to indicate risk of tumour spread; however, a biomarker with greater clinical utility, especially for clinically early-stage cancer, would need to come with increased accuracy. Objective and quantifiable genetic or phenotypic characteristics may add complementary information in the decision of neck management for early-stage oral cancer. With the aims of identifying putative biomarkers that are clinically applicable, I analyzed the genetic, by microRNA sequencing and immune gene expression using NanoString technology, and phenotypic, by image analysis of nuclear phenotype, from surgical primary tumours of oral squamous cell carcinoma (OSCC). The analysis provided predictive marker panels modeled through training and test sets of surgical tissues. Of note, I identified miRNAs and immune genes that were overexpressed in tumours with nodal disease and further suggested a possible inverse relationship between the markers. In addition, I characterized the cancer nuclear phenotype of OSCC and developed a machine-leaning-based cell classification algorithm that can be applied to characterize any area of interests on both nuclear and spatial resolution. I presented predictive biomarker panels that outperforms conventional pathological criteria for neck management of clinically early-stage OSCC. By integrating the results from each aim, I also proposed a patient triage algorithm for elective neck dissection. Overall, the research presented in this thesis is a major step forward in our understanding of the biological alterations that can differentiate high-risk OSCC of nodal disease. Due to its detrimental impact on patient outcomes, the need for objective biomarkers for nodal disease is urgent. The findings generated from robust technologies on routine clinical samples demonstrate great promise in developing new strategies for risk stratification with biomarkers that could be clinically applicable in guiding elective neck dissection. Through early intervention and avoidance of unnecessary procedures, the outcomes of OSCC can be improved.
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