HCK can serve as novel prognostic biomarker and therapeutic target for Breast Cancer patients

Int J Med Sci. 2020 Sep 30;17(17):2773-2789. doi: 10.7150/ijms.43161. eCollection 2020.

Abstract

The role of HCK expression in the prognosis of breast cancer patients is unclear. Thus, this study aimed to explore the clinical implications of HCK expression in breast cancer. We assessed HCK expression and genetic variations in breast cancer using Oncomine, GEPIA, UALCAN, and cBioPortal databases. Then, immunochemistry was used to analyze HCK expression in breast cancer specimens, non-cancer tissues and metastatic cancer tissues. Consequently, we evaluated the effect of HCK expression on survival outcomes set as disease-free survival (DFS) and overall survival (OS). Finally, STRING, Coexpedia, and TISIDB database were explored to identify the molecular functions and regulation pathways of HCK. We found that breast cancer tissues have more HCK mRNA transcripts than non-cancer tissues. Patients with HCK expression had significantly shorter DFS and OS. The ratio of HCK expression was higher in cancer tissues than in non-cancer tissues. These results from STRING database, FunRich software, and TISIDB database showed that HCK was involved in mediating multiple biological processes including immune response-regulating signaling pathway, cell growth and maintenance through multiple signaling pathways including epithelial to mesenchymal transition, PI3K/AKT signaling pathway, and focal adhesion. Overall, HCK may be an oncogene in the development of breast cancer and thus may as a novel biomarker and therapeutic target for breast cancer.

Keywords: HCK; bioinformatic; biomarker; breast cancer; prognosis.

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / mortality*
  • Carcinoma, Ductal, Breast / therapy
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Focal Adhesions / drug effects
  • Focal Adhesions / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunochemistry
  • Mastectomy
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Phosphatidylinositol 3-Kinases
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-hck / antagonists & inhibitors
  • Proto-Oncogene Proteins c-hck / blood
  • Proto-Oncogene Proteins c-hck / genetics*
  • Risk Assessment / methods
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • HCK protein, human
  • Proto-Oncogene Proteins c-hck
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt