Ruolun Wei

All Publications

• VCAN in the extracellular matrix drives glioma recurrence by enhancing cell proliferation and migration. Frontiers in neuroscience Wei, R., Xie, H., Zhou, Y., Chen, X., Zhang, L., Bui, B., Liu, X. 2024; 18: 1501906

  Abstract

  Gliomas are the most prevalent primary malignant intracranial tumors, characterized by high rates of therapy resistance, recurrence, and mortality. A major factor contributing to the poor prognosis of gliomas is their ability to diffusely infiltrate surrounding and even distant brain tissues, rendering complete total resection almost impossible and leading to frequent recurrences. The extracellular matrix (ECM) plays a key role in the tumor microenvironment and may significantly influence glioma progression, recurrence, and therapeutic response.In this study, we first identified the ECM and the Versican (VCAN), a key ECM protein, as critical contributors to glioma recurrence through a comprehensive analysis of transcriptomic data comparing recurrent and primary gliomas. Using single-cell sequencing, we revealed heterogeneous distribution patterns and extensive intercellular communication among ECM components. External sequencing and immunohistochemical (IHC) staining further validated that VCAN is significantly upregulated in recurrent gliomas and is associated with poor patient outcomes.Functional assays conducted in glioma cell lines overexpressing VCAN demonstrated that VCAN promotes cell proliferation and migration via the PI3K/Akt/AP-1 signaling pathway. Furthermore, inhibiting the PI3K/Akt pathway effectively blocked VCAN-mediated glioma progression.These findings provide valuable insights into the mechanisms underlying glioma recurrence and suggest that targeting both VCAN and the PI3K/Akt pathway could represent a promising therapeutic strategy for managing recurrent gliomas.

  View details for DOI 10.3389/fnins.2024.1501906

  View details for PubMedID 39554845

  View details for PubMedCentralID PMC11565936

• Glioma actively orchestrate a self-advantageous extracellular matrix to promote recurrence and progression BMC CANCER Wei, R., Zhou, J., Bui, B., Liu, X. 2024; 24 (1): 974

  Abstract

  The intricate interplay between cancer cells and their surrounding microenvironment has emerged as a critical factor driving the aggressive progression of various malignancies, including gliomas. Among the various components of this dynamic microenvironment, the extracellular matrix (ECM) holds particular significance. Gliomas, intrinsic brain tumors that originate from neuroglial progenitor cells, have the remarkable ability to actively reform the ECM, reshaping the structural and biochemical landscape to their advantage. This phenomenon underscores the adaptability and aggressiveness of gliomas, and highlights the intricate crosstalk between tumor cells and their surrounding matrix.In this review, we delve into how glioma actively regulates glioma ECM to organize a favorable microenvironment for its survival, invasion, progression and therapy resistance. By unraveling the intricacies of glioma-induced ECM remodeling, we gain valuable insights into potential therapeutic strategies aimed at disrupting this symbiotic relationship and curbing the relentless advance of gliomas within the brain.

  View details for DOI 10.1186/s12885-024-12751-3

  View details for Web of Science ID 001287535300009

  View details for PubMedID 39118096

  View details for PubMedCentralID PMC11308147

• Evaluation of Oil-Absorbing Film for Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) on Biological Samples. Metabolites Li, J., Wei, R., Meng, Y., Zare, R. N. 2024; 14 (3)

  Abstract

  Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) has proven to be a robust and reliable tool for chemically imaging biological samples such as fungi, animal tissues, and plants, but the choice of the imprint substrate is crucial. It must effectively transfer maximum amounts of species from the sample while preserving the original spatial distribution of detected molecules. In this study, we explored the potential of utilizing an oil-absorbing film, known for its soft nature and excellent lipophilicity, as an imprint substrate for IDESI-MSI on biological samples. To assess the transfer efficiency of the amounts of molecules and molecular patterns, we conducted experiments using mouse brain tissue. The result shows that more than 90% of the analytes can be transferred to the oil-absorbing film from the original tissue. A comparison of IDESI-MSI results between the oil-absorbing film and the original tissue demonstrates the material's capability to transfer most molecules from the original tissue and retain images of different analytes with high spatial fidelity. We extended our investigation to plant imaging, where we applied IDESI-MSI to a cross-section of okra. The oil-absorbing film exhibited promise in this context as well. These findings suggest that IDESI-MSI utilizing the oil-absorbing film holds potential across various research fields, including biological metabolism, chemistry, and clinical research, making this technique widely applicable.

  View details for DOI 10.3390/metabo14030160

  View details for PubMedID 38535320

  View details for PubMedCentralID PMC10972117

• Online calculator to predict early mortality in patient with surgically treated recurrent lower-grade glioma. BMC cancer Wei, R., Zhao, C., Li, J., Yang, F., Xue, Y., Wei, X. 2022; 22 (1): 114

  Abstract

  The aim of this study was to investigate the epidemiological characteristics and associated risk factors of recurrent lower-grade glioma [LGG] (WHO grades II and III) according to the 2016 updated WHO classification paradigm and finally develop a model for predicting early mortality (succumb within a year after reoperation) in recurrent LGG patients.Data were obtained from consecutive patients who underwent surgery for primary LGG and reoperation for tumor recurrence. The end point "early mortality" was defined as death within 1 year after the reoperation. Predictive factors, including basic clinical characteristics and laboratory data, were retrospectively collected.A final nomogram was generated for surgically treated recurrent LGG. Factors that increased the probability of early mortality included older age (P = 0.042), D-dimer> 0.187 (P = 0.007), RDW > 13.4 (P = 0.048), PLR > 100.749 (P = 0.014), NLR > 1.815 (P = 0.047), 1p19q intact (P = 0.019), IDH1-R132H Mutant (P = 0.048), Fib≤2.80 (P = 0.018), lack of Stupp concurrent chemoradiotherapy (P = 0.041), and an initial symptom of epilepsy (P = 0.047). The calibration curve between the prediction from this model and the actual observations showed good agreement.A nomogram that predicts individualized probabilities of early mortality for surgically treated recurrent LGG patients could be a practical clinical tool for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free online software implementing this nomogram is provided at https://warrenwrl.shinyapps.io/RecurrenceGliomaEarlyM/.

  View details for DOI 10.1186/s12885-022-09225-9

  View details for PubMedID 35086512

  View details for PubMedCentralID PMC8796632

• Advanced Diagnosis of Glioma by Using Emerging Magnetic Resonance Sequences. Frontiers in oncology Wei, R. L., Wei, X. T. 2021; 11: 694498

  Abstract

  Glioma, the most common primary brain tumor in adults, can be difficult to discern radiologically from other brain lesions, which affects surgical planning and follow-up treatment. Recent advances in MRI demonstrate that preoperative diagnosis of glioma has stepped into molecular and algorithm-assisted levels. Specifically, the histology-based glioma classification is composed of multiple different molecular subtypes with distinct behavior, prognosis, and response to therapy, and now each aspect can be assessed by corresponding emerging MR sequences like amide proton transfer-weighted MRI, inflow-based vascular-space-occupancy MRI, and radiomics algorithm. As a result of this novel progress, the clinical practice of glioma has been updated. Accurate diagnosis of glioma at the molecular level can be achieved ahead of the operation to formulate a thorough plan including surgery radical level, shortened length of stay, flexible follow-up plan, timely therapy response feedback, and eventually benefit patients individually.

  View details for DOI 10.3389/fonc.2021.694498

  View details for PubMedID 34422648

  View details for PubMedCentralID PMC8374052

• Behavior-Oriented Nomogram for the Stratification of Lower-Grade Gliomas to Improve Individualized Treatment. Frontiers in oncology Wei, R. L., Zhang, L. W., Li, J. G., Yang, F. D., Xue, Y. K., Wei, X. T. 2020; 10: 538133

  Abstract

  Secondary glioblastomas (sGBM) are derived from previously lower-grade [World Health Organization (WHO) grades II or III] gliomas. Lower-grade benign-behaving gliomas may retain their former grade following recurrence, or may become malignant higher-grade glioblastomas. Prediction of tumor behavior in lower-grade gliomas is critical for individualized glioma therapy. A total of 89 patients were included between January 2000 and January 2019 in the present study to establish a nomogram via univariate and multivariate logistic regression analyses. Nomogram predictive performance was tested in the validation group. We then analyzed 36 O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated lower-grade gliomas from patients seen at West China Hospital of Sichuan University. Survival statistics were calculated with the Kaplan-Meier method. Two clinical factors (molecular diagnosis and WHO grade), five radiological factors (location, cortical involvement, multicentricity, uniformity, and margin enhancement), one biomarker (1p19q codeletion), and a combination of three biomarkers (IDH+/ATRX-/TP53-) were associated with glioma upgrading. Nomograms positive for these prognostic factors had an AUC of 0.880 in the derivation group and 0.857 in the validation group. The calibration and score-stratified survival curves for the derivation group and validation group were good. An operational nomogram was published at https://warrenwrl.shinyapps.io/DynNomapp/. The overall survival of secondary gliomas in the MGMT-unmethylated cohort were influenced independently by the use of temozolomide during the treatment of formerly low-grade gliomas (p=0.00096). Clinical and radiological factors and biomarker-based behavior-oriented nomograms may offer a feasible identification tool for the detection of sGBM precursors. This method may further assist neurosurgeons with the stratification of lower-grade glioma cases and thus the development of better, more individualized treatment plans.

  View details for DOI 10.3389/fonc.2020.538133

  View details for PubMedID 33392065

  View details for PubMedCentralID PMC7774016

• A Hematological-Related Prognostic Scoring System for Patients With Newly Diagnosed Glioblastoma. Frontiers in oncology Zhao, C., Li, L. Q., Yang, F. D., Wei, R. L., Wang, M. K., Song, D. X., Guo, X. Y., Du, W., Wei, X. T. 2020; 10: 591352

  Abstract

  Glioblastoma is the most common primary malignant brain tumor. Recent studies have shown that hematological biomarkers have become a powerful tool for predicting the prognosis of patients with cancer. However, most studies have only investigated the prognostic value of unilateral hematological markers. Therefore, we aimed to establish a comprehensive prognostic scoring system containing hematological markers to improve the prognostic prediction in patients with glioblastoma.A total of 326 patients with glioblastoma were randomly divided into a training set and external validation set to develop and validate a hematological-related prognostic scoring system (HRPSS). The least absolute shrinkage and selection operator Cox proportional hazards regression analysis was used to determine the optimal covariates that constructed the scoring system. Furthermore, a quantitative survival-predicting nomogram was constructed based on the hematological risk score (HRS) derived from the HRPSS. The results of the nomogram were validated using bootstrap resampling and the external validation set. Finally, we further explored the relationship between the HRS and clinical prognostic factors.The optimal cutoff value for the HRS was 0.839. The patients were successfully classified into different prognostic groups based on their HRSs (P < 0.001). The areas under the curve (AUCs) of the HRS were 0.67, 0.73, and 0.78 at 0.5, 1, and 2 years, respectively. Additionally, the 0.5-, 1-y, and 2-y AUCs of the HRS were 0.51, 0.70, and 0.79, respectively, which validated the robust prognostic performance of the HRS in the external validation set. Based on both univariate and multivariate analyses, the HRS possessed a strong ability to predict overall survival in both the training set and validation set. The nomogram based on the HRS displayed good discrimination with a C-index of 0.81 and good calibration. In the validation cohort, a high C-index value of 0.82 could still be achieved. In all the data, the HRS showed specific correlations with age, first presenting symptoms, isocitrate dehydrogenase mutation status and tumor location, and successfully stratified them into different risk subgroups.The HRPSS is a powerful tool for accurate prognostic prediction in patients with newly diagnosed glioblastoma.

  View details for DOI 10.3389/fonc.2020.591352

  View details for PubMedID 33363021

  View details for PubMedCentralID PMC7758450

• Long noncoding RNA ENST00000413528 sponges microRNA-593-5p to modulate human glioma growth via polo-like kinase 1. CNS neuroscience & therapeutics Zhang, R., Wei, R. L., Du, W., Zhang, L. W., Du, T., Geng, Y. D., Wei, X. T. 2019; 25 (8): 842-854

  Abstract

  In this study, we examined the expression of lncRNA ENST00000413528 in glioma and determined its role in glioma development.LncRNA ENST00000413528 was detected in glioma tissues by lncRNA microarray. Then, we performed real-time PCR, CCK-8, colony formation assay, flow cytometry, caspase-3/7 assay and animal experiment to detect the function of ENST00000413528 in glioma after ENST00000413528 knockdown. Subsequent bioinformatics analysis, luciferase reporter assays and RNA immunoprecipitation (RIP) assay western blotting indicated possible downstream regulatory molecules. The expression of PLK1 in glioma tissues was also examined by immunohistochemistry staining.Expression of ENST00000413528 was significantly increased in glioma tissues and LN229 and U251 cells. PLK1 protein could not be detected in peritumoral brain edema (PTBE) tissues; however, it showed an increasing number of positively cytoplasmic stained from WHO-Grade II to Grade III gliomas. Knockdown of ENST00000413528 in glioma cells inhibited cell proliferation and colony formation abilities, induced the G0/G1 arrest of the cell cycle, and promoted apoptosis. The dual reporter assay and RNA immunoprecipitation assay verified the interaction between ENST00000413528 and miR-593. We also demonstrated that polo-like kinase 1 (PLK1) was regulated by miR-593; PLK1 messenger RNA lacking 3'UTR partially reversed the effects caused by ENST00000413528 knockdown or miR-593 upregulation.lncRNA ENST00000413528 is closely related to the development of glioma via the miR-593-5p/PLK1 pathway.

  View details for DOI 10.1111/cns.13121

  View details for PubMedID 30924320

  View details for PubMedCentralID PMC6630009