Data · dataset · 2026
Molecular evolution of aggressive early stage colorectal cancer
Listed in ZivaHub and Deakin Research Online and DMU Figshare — shown once because both records carry DOI 10.17034/32639394.v1
Colorectal cancer (CRC) is a heterogenous disease and many groups have taken advantage of inter-patient heterogeneity to stratify CRC tumours, using transcriptional or histological data, into subtypes/subgroups with similar molecular and pathological features.
Description
A recurring poor prognostic feature in each of these studies is the enrichment of a stromal components within the tumour microenvironment, which is a defining characteristic of the consensus molecular subtype 4 (CMS4).
In addition to being the worst prognostic subtype relative to the other CMS’s, CMS4 tumours derive no benefit from current standard of care therapies meaning that there is an urgent need to identify efficacious therapeutic interventions for this subtype. To address this issue, this project focused on identifying the difference between stroma-rich high fibroblast (HiFi) tumours that relapse compared to those that don’t relapse after surgery. <br><br>Using an in silico analysis comparing the non-relapse and relapse HiFi samples, a n=7 gene list was created called the HiFi-specific prognostic signature (HPS), which was able to stratify the HiFi tumours into good prognostic (high HPS) and poor prognostic (low HPS) subgroups.
Read the rest (3 more)
To characterise the biology underpinning the HPS, differences within the multiple compartments of a tumour ecosystem were investigated, including the stroma and epithelial cells (chapter 1) and immune cells (chapter 2). Tumours with high HPS signalling were enriched for a double-stranded RNA/viral response upstream of an interferon signalling cascade, represented both by gene set analysis and transcription factor activity.
This biology was coupled with the activation of an immune response and an upregulation of antigen processing and presentation. The potential value of using the synthetic dsRNA compound Polyinosinic-polycytidylic acid (poly(I:C)) to induce these HPS-related biological phenotypes was identified and validated across multiple cell lines. The therapeutic efficacy of poly(I:C) in a stroma-rich setting was also investigated within an in vivo experiment, where the treatment resulted in significantly lower metastatic burden than the control group (chapter 3).
The application of poly(I:C)-induced biology along with the understanding of HPS biology then enabled CRC samples to be aligned across an immune landscape, supporting potential therapeutic positioning of poly(I:C). <br><br>In summary, this work supports the use of poly(I:C) as a new therapeutic option for a subgroup of CRC tumours that have the worst prognosis along with no current therapeutic intervention. <br><br><i>Thesis is embargoed until 31 July 2028.</i><br>
Links
Where it is published
- DOI doi.org/10.17034/32639394.v1 ↗
DOI / persistent id · from zivahub uct ac za
Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
metadata API · from zivahub uct ac za
Topics
- From keywords
- Cancer · Cancer · Cancer · Earth & Environmental Science · Earth & Environmental Science · Earth & Environmental Science · Medicine & Health · Medicine & Health · Medicine & Health
- Inferred from text
- Disease 75% · Oncology and carcinogenesis 71%
Provenance · 3 source records, 16 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ZivaHub | oai:figshare.com:article/32639394 | 11 d ago | JSON v1 |
| Deakin Research Online | oai:figshare.com:article/32639394 | 11 d ago | JSON v1 |
| DMU Figshare | oai:figshare.com:article/32639394 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[disease].local:disease:cancer | mapping · dro deakin edu au | vocabulary-mapper@1.0.0 | keywords['cancer'] |
| concepts[disease].local:disease:cancer | mapping · zivahub uct ac za | vocabulary-mapper@1.0.0 | keywords['cancer'] |
| concepts[disease].local:disease:cancer | mapping · figshare dmu ac uk | vocabulary-mapper@1.0.0 | keywords['cancer'] |
| concepts[disease].local:disease:disease | enrichment · zivahub uct ac za | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].anzsrc:group:3211 | enrichment · zivahub uct ac za | taxonomy-embedding@1.1.0 | title+keywords+description (71%) |
| concepts[field].local:field:earth-environmental | mapping · dro deakin edu au | connector:dro_deakin_edu_au@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · figshare dmu ac uk | connector:figshare_dmu_ac_uk@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · figshare dmu ac uk | connector:figshare_dmu_ac_uk@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · dro deakin edu au | connector:dro_deakin_edu_au@1.0.0 | |
| description | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/description |
| license_text | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| publication_date | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| title | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/title |