Abstract 5125: Biological and clinical value of OCT4A/SPP1C axis in endometrial and lung adenocarcinoma

Abstract

Abstract Background: It is largely unclear whether octamer-binding transcription factor 4A (OCT4A, OCT3/4A) functions physiologically or pathologically in adult somatic tissues and related cancers. We have recently identified OCT4A translation in a human cancer cell subpopulation that might exacerbate cell migration and invasion. Here, we focus on biological and clinical features of OCT4A and its relationship with secreted phosphoprotein 1(SPP1), which is strongly related to the malignant progression of numerous tumors. Methods: RT-PCR or qPCR analysis was used to identify full-length spliced forms of OCT4A and SPP1 transcripts in non-tumor and tumor human cells. An OCT4A-FLAG-tagged genomic transgene identified OCT4A-positive cancer cells. Cell-ablation of OCT4A-positive cells using promoter-driven diphtheria toxin A was used to examine the potential role of OCT4A in lung and endometrial adenocarcinoma cells. OCT4A and SPP1 transcripts in early-stage lung adenocarcinoma (stage I, fifty-eight cases) were analyzed and compared with pathohistological and prognostic features. Results: We found that OCT4A and SPP1C are co-expressed in highly aggressive human lung and endometrial adenocarcinoma cell lines but not in mesothelioma or non-tumor cell lines. Ablation of OCT4A-positive cells significantly decreased cancer-cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinomas, and all four cases of recurrence and/or metastasis out of 58 cases were included in the OCT4A and SPP1C positive group. Conclusions: Co-expression of OCT4A and SPP1C may correlate with human cancer cell migration and the OCT4A/SPP1C axis may have a prognostic value in high-risk, early-stage lung adenocarcinomas.