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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer
Yaoqing Li1, Chuchu Xu1, Renjun Zhu2
1Department of Gastrointestinal Surgery, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
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.
