466P - Integrated analysis of potential prognosis and differential expression between primary and metastatic foci for COL12A1 in breast cancer

Background

Extracellular matrix (ECM) plays a key role in tumorigenesis and progression. Collagen XII, expressed by the COL12A1 gene, is an important component of the ECM. COL12A1 is associated with tumorigenesis and poor prognosis in several cancers, but its role in breast cancer (BC) is unclear, especially the different expression between primary and metastasic foci of BC has not been reported.

Methods

We analyzed the expression of COL12A1 in tumor tissue and normal tissue, plotted a Kaplan-Meier curve by GEPIA, and analyzed mutation by COSMIC and cBioPortal in BC. PPI, GGI and pathway and process enrichment analysis were performed by STRING and Metascape. GeneMANIA was used to map gene interaction networks. BC cases with paired primary and metastatic foci were found out from TCGA database for analyzing different expression of COL12A1 in primary and metastatic foci. Immunohistochemical (IHC) staining was performed in paraffin tissue samples of paired primary lesion and lung metastases from triple-negative breast cancer (TNBC) patients.

Results

The results showed that COL12A1 in BC tissues was upregulated and was associated with poor prognosis of BC and the Luminal A+Luminal B subgroup. 3.04% of BC patients had COL12A1 gene alteration. Missense substitution (37.59%) was the most frequent mutation type. Among the 10 related genes, COL3A1, COL5A2, MMP12, P4HA1, P4HA2, P4HA3 and SERPINH1 were significantly upregulated in tumor tissue. The 20 most relevant genes in the GGI network are COL11A1, ID1, COL8A1, MMP9, COL5A1, MMP2, ISLR, LUM, COL7A1, COL3A1, COL1A2, MMP3, COL10A1, COL6A1, COL11A2, COL8A2, MMP8, MMP12. SERPINH1 and MMP13, which are enriched in several pathways including collagen degradation, collagen formation, collagen metabolic process, endodermal cell differentiation, collagen fibril organization and so on. Furthermore, analysis of paired cases from the TCGA-BRCA database revealed that COL12A1 was expressed with higher level in primary foci than metastatic foci. IHC staining revealed that the expression of COL12A1 was upregulated in primary foci of TNBC.

Conclusions

In conclusion, COL12A1 may be a poor prognostic predictor and a specific therapeutic target for primary foci in BC, especially in TNBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Suzhou Science and Technology Developing Projects (SKYD2022083, SYSD2020079 and SYSD2020075).

Disclosure

All authors have declared no conflicts of interest.