Cancer-associated fibroblasts in uterine corpus endometrial carcinoma.

Abstract

e17618 Background: The general role of cancer-associated fibroblasts (CAFs) and their invasive characteristics in Uterine Corpus Endometrial Carcinoma (UCEC) remain unknown. CAFs serve as an important component of the tumor microenvironment and promote tumorigenesis and cancer aggressiveness. Methods: UCEC mRNA data were downloaded from TCGA cBioPortal ( http://www.cbioportal.org/ ). CAF levels were estimated by three algorithms: MCPCOUNTER, XCELL, and EPIC, so three CAF scores were gotten and ranked. Then, the data of CAF scores in each cohort were divided into quarters, and we labeled the sample by upper quartile and lower quartile with “high”, “medium”, and “low”. To mitigate the possible classification error from each estimation method, we defined samples as “high” by at least two methods consistently labeling “high”. Samples labeled with “low” by at least two methods were assigned to the consensual low CAF group. The high and low group were analysis using GSEA software, Survival analysis was performed using the R package “survival”. Results: There were 129, 118 and 280 samples in the high, low and middle CAFs group, respectively. GSEA results showed extensive gene expression differences between the high and low CAF groups. 193 gene sets were significantly enriched at nominal p value < 0.01 in the low group, 869 gene sets were significantly enriched at nominal p value < 0.01 in the high group. In the low group, obvious differences, included lim mammary stem cell up, reactome degradation of the extracellular matrix, bertucci medullary vs ductal breast cancer dn etc. are enriched in the high group. xu akt1 targets 6hr, OUELLET (Gene Set) ovarian cancer invasive vs lmp up etc. are enriched in the low group. OS and PFS survival analysis showed there was no significant difference between these two groups. Conclusions: Our study analyzed the relationship between CAFs with UCEC, CAFs were associated with an immunosuppressive microenvironment. Larger transcriptomic alterations occurred in UCECs with high CAF infiltration, and with AKT, ALCALA APOPTOSIS and SPLICEOSOME pathways prominent in this process. But Survival analysis showed no difference between the two groups.