TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer

  • J Cancer Res Clin Oncol. 2023 Mar 11. doi: 10.1007/s00432-023-04670-w.
Yaoqing Li  1 ,  Chuchu Xu  1 ,  Renjun Zhu  2 ,  Liyijing Shen  3 ,  Gengyuan Hu  1 ,  Kelong Tao  1 ,  Feng Tao  4  5 ,  Zengxin Lu  6  7 ,  Guolin Zhang  8
Affiliations
  • 1. Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
  • 2. Department of Emergency, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
  • 3. Department of Radiology, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
  • 4. Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China. [email protected].
  • 5. Medical School of Shaoxing University, The First Hospital Affiliated to Shaoxing University, Shaoxing, 312000, Zhejiang, China. [email protected].
  • 6. Department of Radiology, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China. [email protected].
  • 7. Medical School of Shaoxing University, The First Hospital Affiliated to Shaoxing University, Shaoxing, 312000, Zhejiang, China. [email protected].
  • 8. Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China. [email protected].
PMID: 36905423 DOI: 10.1007/s00432-023-04670-w
Abstract

Purpose: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal Cancer.

Methods: The 5-Fu resistance of colorectal Cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal Cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance.

Results: Our experimental results display that TIMP-2 expression is elevated in colorectal Cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal Cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal Cancer earlier than tumor volume.

Conclusion: TIMP-2 is a good indicator of 5-Fu resistance in colorectal Cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal Cancer patients earlier during chemotherapy.

Keywords
5-Fu; Biomarker; Colorectal cancer; Drug resistance; TIMP-2.
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