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Published on: February 8, 2018
Proteomics Identifies Circulating TIMP-1 as a Prognostic Biomarker for Diffuse Large B-Cell Lymphoma
Ning Lou1, Guibin Wang2, Yanrong Wang3
1Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.
Researchers classified diffuse large B-cell lymphoma (DLBCL) into four subtypes using plasma proteomics. High levels of tissue metalloproteinase inhibitor-1 (TIMP-1) correlated with poor prognosis, improving patient stratification when combined with the international prognostic index (IPI).
Area of Science:
- Oncology
- Proteomics
- Biochemistry
Background:
- Diffuse large B-cell lymphoma (DLBCL) is a complex and heterogeneous hematologic malignancy.
- Current prognostic models for DLBCL lack the granularity to fully capture disease heterogeneity.
- In-depth plasma proteomic analysis has not been extensively utilized for DLBCL stratification.
Purpose of the Study:
- To stratify DLBCL patients into distinct subtypes based on plasma proteomic profiles.
- To identify novel protein biomarkers associated with prognosis in DLBCL.
- To evaluate the potential of combining proteomic markers with existing prognostic indices for improved patient risk stratification.
Main Methods:
- Plasma samples from 147 DLBCL patients were analyzed using data-independent acquisition mass spectrometry and antibody arrays.
- Over 1000 proteins were quantified to classify patients into proteomic subtypes (PS-I-IV).
- Validation was performed in two independent cohorts (n=180) to confirm findings.
Main Results:
- DLBCL patients were successfully classified into four distinct proteomic subtypes.
- The PS-IV subtype, associated with the poorest prognosis, exhibited elevated levels of inflammation-related proteins.
- High expression of tissue metalloproteinase inhibitor-1 (TIMP-1) was significantly correlated with poor survival.
- Combining TIMP-1 with the international prognostic index (IPI) substantially improved the identification of relapsed and deceased patients compared to IPI alone.
Conclusions:
- Plasma proteomic profiling reveals significant heterogeneity within DLBCL.
- TIMP-1 is a promising biomarker for predicting survival in DLBCL patients.
- The combination of TIMP-1 and IPI offers a more accurate prognostic tool for DLBCL patient stratification.

