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dc.contributor.authorMoss, Adrian C.
dc.contributor.authorJacobson, Gregory M.
dc.contributor.authorWalker, Lauren E.
dc.contributor.authorBlake, Neil W.
dc.contributor.authorMarshall, Ernie
dc.contributor.authorCoulson, Judy M.
dc.identifier.citationMoss, A. C., Jacobson, G. M., Walker, L. E., Blake, N. W., Marshall, E., & Coulson, J. M. (2009). SCG3 transcript in peripheral blood Is a prognostic biomarker for REST-deficient small cell lung cancer. Clinical Cancer Research, 15(1), 274-283.en_NZ
dc.description.abstractPurpose: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood. Experimental Design: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals. Results: Expression profiling revealed multiple chromogranin transcripts were readily induced on REST depletion, most notably SCG3 was induced >500-fold. The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022). Conclusions: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.en_NZ
dc.publisherAmerican Association for Cancer Researchen_NZ
dc.relation.ispartofClinical Cancer Research
dc.subjectsecretogranin IIIen_NZ
dc.subjectcirculating tumor cellsen_NZ
dc.titleSCG3 transcript in peripheral blood Is a prognostic biomarker for REST-deficient small cell lung canceren_NZ
dc.typeJournal Articleen_NZ
dc.relation.isPartOfClinical Cancer Researchen_NZ

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