Mesenchymal and Phosphatase of Regenerating Liver-3 Status in Circulating Tumor Cells May Serve as a Crucial Prognostic Marker for Assessing Relapse or Metastasis in Postoperative Patients With Colorectal Cancer

Clin Transl Gastroenterol. 2020 Dec;11(12):e00265. doi: 10.14309/ctg.0000000000000265.

Abstract

Introduction: Circulating tumor cells (CTCs) and phosphatase of regenerating liver-3 (PRL-3) have been considered to be significant prognostic indicators in metastatic colorectal cancer (CRC). This study discusses the prognostic significance of mesenchymal CTCs with PRL-3 (M+ PRL-3+ CTCs) in postoperative patients with CRC.

Methods: We detected CTC subtypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) and PRL-3 in CTCs from the peripheral blood samples of 156 patients. Receiver operating characteristic curve analysis, Kaplan-Meier analysis, and Cox proportional hazards regression analysis were performed to identify the prognostic value of mesenchymal CTCs with PRL-3+. Immunohistochemistry was used to detect the expression of PRL-3 in tumor tissues from some of the patients to explore the connection between CTCs and tissues.

Results: All CTCs were positive in all samples, both mesenchymal CTCs and PRL-3-positive cells. The count of mesenchymal and PRL-3+ CTCs was significantly associated with recurrence, and the optimal cutoff value was 2 (area under the curve = 0.690, P < 0.001). In addition, these patients had a significantly shorter median disease-free survival than those who did not fulfill the criteria (8.5 vs 24 months, P < 0.001) according to multivariable and multinomial logistic regression. Immunohistochemistry was applied to explore the associations between PRL-3 expression and significant prognostic risk factors, including recurrence (R = 0.566; P < 0.001), and M+ PRL-3+ status in CTCs (R = 0.452; P = 0.001).

Discussion: The status of M+ PRL-3+ in CTCs may serve as a crucial prognostic marker for assessing clinical outcomes in CRC.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Colectomy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / metabolism*
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Proctectomy
  • Prognosis
  • Prospective Studies
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / metabolism*
  • ROC Curve
  • Risk Assessment / methods
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases