Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC
Lung cancer is the main cause of cancer mortality worldwide. Approximately ∼80% of lung cancer cases are non-small cell lung cancer (NSCLC) in type and >50% of NSCLC are adenocarcinoma in histopathology. A shifting paradigm in the field of pulmonary oncology is the identification of molecular markers that are therapeutic targets and/or provide prognostic information. The recent recognition of the role biomarkers such as EGFR, KRAS, and ALK play in NSCLC adenocarcinoma patients demonstrates this trend. Although these three highly characterized molecular markers make up one-quarter to two-thirds of NSCLC adenocarcinoma patients, the remaining population, termed “Triple-Negative Lung Cancer” (TNLC), has yet to be fully defined. The complete absence of therapeutic targets for triple-negative lung cancer patients undeniably supports the need to identify up-regulated and mutated genes that better define this poor prognostic cohort. Recent genome-wide expression profiles subdivided TNLC patients into a poor prognostic group based on the overexpression of the DEP domain containing 1 gene (DEPDC1) (Okayama et al., 2011). We hypothesized that overexpression of DEPDC1 correlates with a specific sub-population of adenocarcinoma patients. Our initial studies indicate that DEPDC1 is constitutively expressed in both normal lung as well as lung cancer specimens. DEPDC1 transcripts are present as two variants (V1 and V2), with constitutive expression of the V1 variant in normal lung. We hypothesized that expression of the V2 transcript could be unique to NSCLC adenocarcinomas. Screening of FFPE NSCLC adenocarcinoma specimens using a proprietary qPCR approach demonstrated the presence of the DEPDC1 V2 variant but at levels that were not sufficient to serve as a sole biomarker. We therefore investigated whether the ratio of DEPDC1 V2 expression relative to V1 could serve as a biomarker in TNLC. Our preliminary data suggest that the ratio of V2 to V1 expression of DEPDC1 does in fact segregate TNLC into specific sub-populations. These studies have exciting diagnostic as well as therapeutic implications as Phase I/II studies using novel peptide vaccines derived against DEPDC1 have proven tolerable and efficacious for patients with bladder cancer and could potentially be extended to target these newly identified TNLC sub-populations.
Citation Format: Brock L. Schweitzer, Kasey D. Lawrence, John Handshoe, Rachel Skelton, Lindsay Chatfield, Liquan Xue, Stephan W. Morris, David R. Hout. The unknown piece of the pie: Molecular markers in triple-negative lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1930. doi:10.1158/1538-7445.AM2013-1930