PPP4C: a potential molecular marker and therapeutic target in thyroid cancer and triple-negative breast cancer

  • BMC Cancer. 2026 May 4;26(1):768. doi: 10.1186/s12885-026-16083-2.
Huashui Li  #  1  2 Yifan Chen  #  1  3 Guodong Guo  #  4 Qinghua Luo  5 Qiang Lin  2 Wenjun Xie  6  7 Maolin Yan  8  9
Affiliations
  • 1. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, 350001, People's Republic of China.
  • 2. Department of Thyroid & Hernia Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China.
  • 3. Department of Breast Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China.
  • 4. Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China.
  • 5. Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China.
  • 6. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, 350001, People's Republic of China. [email protected].
  • 7. Department of Thyroid & Hernia Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China. [email protected].
  • 8. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, 350001, People's Republic of China. [email protected].
  • 9. Department of Hepatobiliary Pancreatic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

The protein Phosphatase PPP4C has been implicated in oncogenic processes, but its role in thyroid carcinoma (THCA) and triple-negative breast Cancer (TNBC) remains unclear. Here, we combined bioinformatic analyses with in vitro experiments to investigate the clinical and functional significance of PPP4C in these malignancies. PPP4C was significantly upregulated in both THCA and TNBC compared with normal tissues, and higher expression was associated with adverse clinicopathological features and poorer overall survival. Functional assays showed that PPP4C knockdown suppressed proliferation, migration, and invasion in TNBC and THCA cell lines, supporting a pro-tumorigenic role in vitro. Integrative analyses further suggested that elevated PPP4C expression is associated with oncogenic signaling pathways, RNA modification-related genes, and immune-related characteristics. Drug sensitivity prediction analysis indicated differential responsiveness to selected targeted agents, and experimental validation demonstrated that PPP4C depletion enhances sensitivity to specific inhibitors in vitro. Overall, PPP4C is consistently overexpressed and functionally relevant in THCA and TNBC. PPP4C may represent a candidate biomarker associated with tumor progression and therapeutic response, warranting further mechanistic and in vivo investigation.

Keywords
Biomarker; Drug sensitivity; PPP4C; Targeted therapy; Thyroid cancer; Triple-negative breast cancer.
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