Analysis of neuroendocrine clones in NSCLCs using an immuno-guided laser-capture microdissection-based approach

Elisa Baldelli, Martina Mandarano, Guido Bellezza, Emanuel F. Petricoin, Mariaelena Pierobon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Clonal evolution and lineage plasticity are key contributors to tumor heterogeneity and response to treatment in cancer. However, capturing signal transduction events in coexisting clones remains challenging from a technical perspective. In this study, we developed and tested a signal-transduction-based workflow to isolate and profile coexisting clones within a complex cellular system like non-small cell lung cancers (NSCLCs). Cooccurring clones were isolated under immunohistochemical guidance using laser-capture microdissection, and cell signaling activation portraits were measured using the reverse-phase protein microarray. To increase the translational potential of this work and capture druggable vulnerabilities within different clones, we measured expression/activation of a panel of key drug targets and downstream substrates of FDA-approved or investigational agents. We isolated intermixed clones, including poorly represented ones (<5% of cells), within the tumor microecology and identified molecular characteristics uniquely attributable to cancer cells that undergo lineage plasticity and neuroendocrine transdifferentiation in NSCLCs.

Original languageEnglish
Article number100271
JournalCell Reports Methods
Issue number8
StatePublished - 22 Aug 2022
Externally publishedYes


  • immuno-guided laser capture microdissection
  • neuroendocrine transdifferentiation
  • non-small cell lung cancer
  • phosphoproteome
  • reverse-phase protein microarray
  • signal transduction


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