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ASPM Predicts Poor Clinical Outcome and Promotes Tumorigenesis for Diffuse Large B-cell Lymphoma
Jingjing Wu1, Zhengmei He1, Yaning Zhu2
1Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
Background:
Abnormal spindle-like microcephaly-associated protein (ASPM) has been implicated in the aggressive behavior of several malignant tumors. However, its potential effects on diffuse large B-cell lymphoma (DLBCL) still remain unknown.
Methods:
ASPM levels were determined by immunohistochemically in DLBCL tissues from 54 patients and 15 reactive lymphoid hyperplasia (RLH) tissues as control, and its association with clinical features and overall survival were evaluated. The effects of ASPM on cell growth, cell apoptosis and cell cycle of DLBCL cells were assessed. Bioinformatics, quantitative RT-PCR and western blotting were conducted for mechanic investigation.
Results:
ASPM expression was upregulated in DLBCL tissues compared with RLH tissues. Its high expression was correlated with inferior clinicopathological characteristics and poor outcomes of DLBCL patients. Multivariate analysis revealed that high ASPM expression emerged as an independent factor for poor prognosis. In DLBCL cell lines, silencing of ASPM suppressed cell growth, induced cell apoptosis and arrested the cell cycle. Mechanically, effects of ASPM knockdown on DLBCL cells were partially dependent on its block of the Wnt/β-catenin pathway.
Conclusion:
Collectively, our results suggested that ASPM potentially served as a predictive biomarker of DLCBL tumorigenesis and prognosis, representing a potential therapeutic target for DLCBL.
Insights
Abnormal spindle-like microcephaly-associated protein (ASPM) is upregulated in diffuse large B-cell lymphoma (DLBCL), correlating with poor prognosis. Silencing ASPM inhibits DLBCL cell growth and impacts the Wnt/β-catenin pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Abnormal spindle-like microcephaly-associated protein (ASPM) is linked to aggressive behavior in various cancers.
- The role of ASPM in diffuse large B-cell lymphoma (DLBCL) remains unexplored.
Purpose of the Study:
- To investigate ASPM expression in DLBCL.
- To evaluate the association between ASPM and DLBCL patient outcomes.
- To elucidate the functional role and mechanism of ASPM in DLBCL.
Main Methods:
- Immunohistochemistry was used to assess ASPM levels in DLBCL tissues and controls.
- DLBCL cell lines were utilized to study the effects of ASPM on cell growth, apoptosis, and cell cycle.
- Bioinformatics, quantitative RT-PCR, and western blotting were employed for mechanistic investigations.
Main Results:
- ASPM expression was significantly higher in DLBCL tissues than in reactive lymphoid hyperplasia.
- High ASPM expression correlated with unfavorable clinicopathological features and poorer overall survival in DLBCL patients.
- ASPM knockdown inhibited DLBCL cell proliferation, induced apoptosis, and caused cell cycle arrest, partly via the Wnt/β-catenin pathway.
Conclusions:
- ASPM may serve as a predictive biomarker for DLBCL tumorigenesis and prognosis.
- ASPM represents a potential therapeutic target for diffuse large B-cell lymphoma.
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