Abstract 3993: A microarray-based gene expression analysis identified diagnostic biomarkers for unknown primary cancer

Abstract

Abstract Background: Patients with cancer of unknown primary (CUP) present with metastatic disease for which the primary site cannot be found. Clinically, CUPs exhibit common characteristics, such as rapid progression and early dissemination, with a silent primary tumor that may become involuted and undetectable. Existence of such common properties prompts us to hypothesize that there may be potential biological markers that elucidate CUP as a whole. Methods: Tumor mRNA samples from 60 patients with CUP were measured for the expression of ∼22,000 genes using the Affymetrix U133A Plus 2.0 GeneChip and analyzed by applying normalization and classification algorithms to the gene expression data. The similarity of each tumor specimen's gene expression pattern is then compared to the gene-expression profiles specific to non-CUP groups (containing tumors from 24 known primary sites) that were constructed using publicly available raw microarray datasets. The t-tests were performed to compare the CUP with non-CUP groups and the top 59 CUP specific genes with the highest fold change were selected (p-value < 0.001). Results: This study enabled the identification of genes that exhibited a unique expression pattern in CUP. As a high metastasis potential and vulnerability to apoptosis would explain the properties of CUP well, we first searched for genes related to metastasis and apoptosis and found 14 genes among 44 that were up-regulated by more than 2.5-fold in the CUP samples. Some of these genes were associated with the epithelial-to-mesenchymal transition (EMT), a function that has been increasingly recognized as a key step in cancer metastasis. We also identified 6 genes for ribosomal proteins among 44 up-regulated genes, two of which (RPS7 and RPL11) were known to be involved in the Mdm2 - p53 pathway. Conclusions: The protein products of the up-regulated and down-regulated genes identified in this study suggest a biological attribute of CUP and, therefore, may become clinically useful biomarkers for CUP. Citation Format: Yoshihiko Fujita, Issei Kurahashi, Takayasu Kurata, Yasuhiro Koh, Kazuko Sakai, Kazuhiko Nakagawa, Kazuto Nishio. A microarray-based gene expression analysis identified diagnostic biomarkers for unknown primary cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3993. doi:10.1158/1538-7445.AM2014-3993