Biochemistry Seminar: Holly Pinkney, PhD Candidate
Colorectal cancer (CRC) is a major contributor to the global burden of disease. At present, clinicians are unable to predict which patients will develop recurrent or metastatic disease, and there is no prioritisation system beyond stage of diagnosis for whether a patient receives adjuvant chemotherapy post-resection of their tumour.
There is a high unmet clinical need for the development of biomarkers which predict risk of disease recurrence. While most previous exploration of therapeutic targets and biomarkers have been directed towards proteins, the majority of the transcribed genome comprises non-coding RNA, in particular long non-coding RNAs (lncRNAs). LncRNAs are transcripts of >200 nucleotides in length that do not encode a protein. They are highly suited as biomarkers, due to their superior tissue- and cancer-specific expression compared to protein-coding genes.
In order to discover lncRNAs which could be important as biomarkers, I studied their expression in CRC using spatial transcriptomics. In addition to providing spatial context, this method is superior to bulk RNA sequencing as it better captures lncRNA expression signal, which is cell-type specific and can be lost if expression is only in a small population of cells, for example, the cells driving metastasis.
During the course of my PhD, I have had the privilege of working with the Dunedin Colorectal Cohort (DNCRC). I used spatial transcriptomics to profile primary tumour, adjacent normal and metastatic tissue from two DNCRC patients, and found a number of lncRNAs that were expressed specifically in tumour and metastatic tissues, but not in normal colon tissue. Investigation in silico and using fluorescent in situ hybridisation in tissues from seven further DNCRC patients revealed two candidate lncRNAs which had significantly higher expression in metastatic tissue than primary tumours. These candidates were also detectable in early stage disease prior to recurrence, indicating their potential as predictive markers of recurrence for CRC.
Zoom link: https://otago.zoom.us/j/97756704741