Survivin Expression in Luminal Breast Cancer and Adjacent Normal Tissue for Immuno-Oncology Applications

Int J Mol Sci. 2023 Jul 23;24(14):11827. doi: 10.3390/ijms241411827.

Abstract

Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study.

Keywords: BIRC5; artificial intelligence; bioinformatics; breast cancer; immuno-oncology; next-generation sequencing; survivin; tumor associated antigen.

MeSH terms

  • Breast / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / therapy
  • Carcinoma, Ductal, Breast* / pathology
  • Carcinoma, Intraductal, Noninfiltrating* / metabolism
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Survivin / genetics

Substances

  • Survivin
  • Inhibitor of Apoptosis Proteins

Grants and funding

This research received no external funding.