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SCG3 transcript in peripheral blood is a prognostic biomarker for REST-deficient small cell lung cancer.

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.
AuthorsAdrian C Moss, Gregory M Jacobson, Lauren E Walker, Neil W Blake, Ernie Marshall, Judy M Coulson
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 1 Pg. 274-83 (Jan 1 2009) ISSN: 1078-0432 [Print] United States
PMID19118055 (Publication Type: Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Chromogranins
  • RNA, Messenger
  • SCG3 protein, human
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (blood)
  • Cell Line, Tumor
  • Chromogranins (blood)
  • DNA Fingerprinting
  • Female
  • Humans
  • Lung Neoplasms (blood, drug therapy)
  • Male
  • Middle Aged
  • Neuroendocrine Tumors (blood)
  • Prognosis
  • RNA, Messenger (blood)
  • Small Cell Lung Carcinoma (blood, drug therapy)

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