Radiosensitivity-specific proteomic and signaling pathway network of non-small cell lung cancer.

PURPOSE An unmet clinical need in non-small cell lung cancer (NSCLC) management is the accurate prediction of radiation response in patients receiving radical radiotherapy. We explored the intrinsic radiosensitivity of NSCLC from the proteomic profiles of NSCLC cell lines and paraffin-embedded human samples. EXPERIMENTAL DESIGN To uncover radiosensitivity-specific proteomic and signaling pathways, we performed quantitative proteomics by data-independent acquisition mass spectrometry assay on 29 human NSCLC cell lines and 13 paraffin-embedded human NSCLC samples. Closely interacting radioresistant proteins were validated by western blotting, immunofluorescence, real-time quantitative PCR in NSCLC cell lines, and immunohistochemistry in paraffin-embedded human samples. The functions of three key hub proteins were validated by lentivirus transfection, clonogenic survival assay, and flow cytometry. RESULTS The proteomic profiling of NSCLC showed that the intrinsic radiosensitivity of NSCLC is mainly modulated by signaling pathways of proteoglycans in cancer, focal adhesion, and regulation of the actin cytoskeleton. We identified 71 differentially expressed proteins, and eight closely interacting proteins were validated as radioresistant proteins of NSCLC. Moreover, we also validated the functionality of integrin-linked protein kinase, p21-activated kinase 1, and Ras GTPase-activating-like protein IQGAP1 in the radiation response of NSCLC cell lines. Finally, with the NSCLC radiosensitivity-specific proteins, we delineated the atlas network of NSCLC radiosensitivity-related signaling pathways. CONCLUSION Radiosensitivity-specific proteins have the potential to guide individualized radiotherapy in clinical practice by predicting the radiation response of patients with NSCLC. Moreover, the NSCLC radiosensitivity-related signaling pathway atlas could guide further exploration of the underlying mechanism.

• Publication year

  2021

• Venue

  International Journal of Radiation Oncology, Biology, Physics

• Publication date

  2021-09-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.ijrobp.2021.08.041PMID 34506873
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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