Investigating the relationship between proteomic and transcriptomic expression of key immune markers in HGSOC and their clinical relevance for patients.


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Laura Webster1,Manuel Salto-Tellez1,Darragh McArt1,Charlie Gourley2,Richard Kennedy1,Stephanie Craig1,Robb Hollis2,Matthew Alderdice1
1CCRCB,2University of Edinburgh

Abstract

Background

Ovarian cancer is the second most common gynaecological disease in the UK.  High grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and represents about 90% of ovarian serous carcinomas. Survival rates have changed little since the introduction of platinum-based therapies over 30 years ago.  HGSOC was one of the first human cancers to find an association between increased density of intraepithelial tumour-infiltrating lymphocytes (TILs) and longer overall survival.  Pathological assessment of the immune contexture using immunohistochemistry has been shown to successfully stratify patients for response to chemotherapy in other cancer types. This study investigates the use of the R package, MCPCounter, on gene expression values for HGSOC patients to establish whether the immune contexture can be determined in the absence of proteomic data.

Method

The density of intratumoral CD3 and CD8 lymphocytes was investigated by IHC on a tissue microarray of a series of 218 HGSOC patients and analysed using QuPath. The MCPCounter R package was then used to quantify the abundance of the immune cells in the tissues using matching transcriptomic data for these patients. This MCP Counter score was correlated with the IHC results as well as clinical outcome for the patients.

Results

Preliminary results show that MCPCounter scores for CD3 and CD8 correspond with respective high and low CD3/CD8 IHC expression (p<0.001) CD3 IHC showed a strong correlation with MCP CD3 (r = 0.7) However, CD8 showed a weak correlation.  From the gene expression data, only the CD3 MCPCounter score was predictive of survival.

Conclusion

Protein and gene expression of key immune markers carry different clinical predictive value.   MCP is not entirely representative of proteomic analysis using IHC for HGSOC.  Further investigation is required to establish the immune contexture in HGSOC and its potential to stratify patients for chemotherapy.