Lung cancer transcriptomes refined with laser capture microdissection

Juan Lin, Gabrielle Marquardt, Nandita Mullapudi, Tao Wang, Weiguo Han, Miao Shi, Steven Keller, Changcheng Zhu, Joseph Locker, Simon D. Spivack

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


We evaluated the importance of tumor cell selection for generating gene signatures in non-small cell lung cancer. Tumor and nontumor tissue from macroscopically dissected (Macro) surgical specimens (31 pairs from 32 subjects) was homogenized, extracted, amplified, and hybridized to microarrays. Adjacent scout sections were histologically mapped; sets of approximately 1000 tumor cells and nontumor cells (alveolar or bronchial) were procured by laser capture microdissection (LCM). Within histological strata, LCM and Macro specimens exhibited approximately 67% to 80% nonoverlap in differentially expressed (DE) genes. In a representative subset, LCM uniquely identified 300 DE genes in tumor versus nontumor specimens, largely attributable to cell selection; 382 DE genes were common to Macro, Macro with preamplification, and LCM platforms. RT-qPCR validation in a 33-gene subset was confirmatory (ρ = 0.789 to 0.964, P = 0.0013 to 0.0028). Pathway analysis of LCM data suggested alterations in known cancer pathways (cell growth, death, movement, cycle, and signaling components), among others (eg, immune, inflammatory). A unique nine-gene LCM signature had higher tumor-nontumor discriminatory accuracy (100%) than the corresponding Macro signature (87%). Comparison with Cancer Genome Atlas data sets (based on homogenized Macro tissue) revealed both substantial overlap and important differences from LCM specimen results. Thus, cell selection via LCM enhances expression profiling precision, and confirms both known and under-appreciated lung cancer genes and pathways.

Original languageEnglish (US)
Pages (from-to)2868-2884
Number of pages17
JournalAmerican Journal of Pathology
Issue number11
StatePublished - Nov 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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