Proteomic Analysis for Finding Serum Pathogenic Factors and Potential Biomarkers in Multiple Myeloma

Zhang, Hongtao; Tian, Enbing; Chen, Yuling; Deng, Haiteng; Wang, Qingtao

doi:10.4103/0366-6999.155112

Cited by 25 publications

(13 citation statements)

References 24 publications

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“…MMRN1 has 2 isoforms, each measuring 138 and 58 kDa, due to alternative splicing. Isoform-1 of MMRN-1 has been identified as a potential serum biomarker for multiple myeloma and lung cancer (49) and urinary biomarker for cervical cancer (57). In the present study, serum levels of isoform-2 of MMRN-1, as confirmed by mass spectrometry, were decreased in the serum of HPV positive normal controls and in patients with early and late stage cervical cancer.…”

Section: Discussionsupporting

confidence: 63%

“…In addition to its role in vitamin D transport, other important biological functions of VDBP include extracellular G-actin scavenging, macrophage activation (immuno-modulatory function) and neutrophil chemotaxis (anti-inflammatory function) (47,48). Previous studies have suggested an association between low levels of VDBP and the risk of several types of cancer, including multiple myeloma, pancreatic, prostate and kidney cancer (49)(50)(51). These previous data were supported by the inverse association between serum VDBP levels and cervical cancer observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

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Identification of potential cervical cancer serum biomarkers in Thai patients

et al. 2020

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Cervical cancer is one of the most common causes of cancer-associated mortality in females worldwide. Serum biomarkers are important tools for diagnosis, disease staging, monitoring treatment and detecting recurrence in different types of cancer. However, only a small number of established biomarkers have been used for clinical diagnosis of cervical cancer. Therefore, the identification of minimally invasive, sensitive and highly specific biomarkers for detection of cervical cancer may improve outcomes. In the present pilot study, changes in disease-relevant proteins in 31 patients with cervical cancer were compared with 16 healthy controls. The Human 14 Multiple Affinity Removal system was used to deplete the 14 most abundant serum proteins to decrease sample complexity and to enrich proteins that exhibited decreased levels of abundance in the serum samples. Immunoaffinity-depleted serum samples were analyzed by in-gel digestion, followed by liquid chromatography mass spectrometry analysis and data processing. Automated quantitative western blot assays and receiver operating characteristic (ROC) curves were used to evaluate the differential protein expression levels between the two groups. Capillary electrophoresis-based western blot analysis was performed to quantitatively determine serum levels of the candidate biomarkers. Significantly increased levels of α-1-antitrypsin (A1AT) and pyrroline-5-carboxylate reductase 2 (PYCR2) were detected, whereas the levels of transthyretin (TTR), apolipoprotein A-I (ApoA-I), vitamin D binding protein (VDBP) and multimerin-1 (MMRN1) were significantly decreased in patients with cervical cancer compared with the healthy controls. ROC curve analysis indicated that the sensitivity and specificity was improved through the combination of the 6 candidate biomarkers. In summary, the results demonstrated that 6 candidate biomarkers (A1AT, PYCR2, TTR, ApoA-I, VDBP and MMRN1) exhibited significantly different expression between serum samples from healthy controls and patients with cervical cancer. These proteins may represent potential biomarkers for distinguishing patients with cervical cancer from healthy controls and for differentiation of patient subgroups.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Identification of potential cervical cancer serum biomarkers in Thai patients

et al. 2020

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“…Such correlation has also been reported in lung cancer, breast cancer and nasopharyngeal cancer [24]. A proteomic analysis has identified 22 proteins in myeloma patients that have a different level of expression from healthy controls, among which Apo A1 was found down regulated in myeloma patients [25], while the exact mechanism under these phenomenon was still unknown. An experiment by Maryam et al has indicated that Apo A1 might have potent anti-tumorigenic effects on melanoma cells through several different mechanisms: increase CD8 T cell expression, increase anti-tumor macrophages, decrease angiogenesis, inhibit tumor growth, and reduce tumor invasion and metastasis [15].…”

Section: Discussionmentioning

confidence: 55%

Identification of High Serum Apolipoprotein A1 as a Favorable Prognostic Indicator in Patients with Multiple Myeloma

Liang¹,

Li²,

Fu³

et al. 2019

J. Cancer

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This study is to explore the prognostic significance of serum lipid profiles in patients with multiple myeloma (MM). The study retrospectively enrolled 307 MM patients in Zhongshan Hospital, Shanghai, China, from 2007 to 2016. We evaluated the prognostic significance of the pre-diagnostic serum lipid profile [cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), Apolipoprotein A1 (Apo A1) and Apolipoprotein B (Apo B)]. Prognostic factors identified through univariate and multivariate analysis were used to construct a new model based on Lasso Cox regression. Results indicated that lipid levels showed significant difference between ISS stages: Apo A1, Apo B, Cholesterol and LDL levels were lower in late ISS stage. However, only Apo A1 showed statistically significance in overall survival (OS), progression free survival (PFS) and cause specific survival (CSS) (P=0.038, P=0.028, P=0.011) in univariate Cox regression. Patients with higher Apo A1 displayed longer OS (median OS, 67 months vs. 30 months; P<0.001). Also, Apo A1 was revealed to be an independent prognostic indicator through multivariate analysis. Combining the Apo A1 level, Zhongshan Score model was constructed with Lasso regression for prognosis prediction. This model exhibited higher accuracy than International Staging System (ISS) and Durie and Salmon (DS) system. In conclusion, among all the serum lipid profiles, serum Apo A1 is a powerful prognostic indicator for patients with MM.

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“…Dowling et al focused on biomarkers of bone disease in myeloma and identified 24 proteins (six of which were downregulated) including complement proteins and extracellular matrix glycoproteins [97], while Zhang et al found 22 proteins (10 downregulated) [98]. …”

Section: Future Developmentsmentioning

confidence: 99%

Towards Stratified Medicine in Plasma Cell Myeloma

Egan¹,

Drain²,

Conway³

et al. 2016

IJMS

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Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient’s age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies. Clinical staging, recurring acquired cytogenetic aberrations, and serum biomarkers such as β-2 microglobulin, and free light chains are in widespread use but often fail to predict the disease progression or inform treatment decision making. Recent scientific advances have provided considerable insight into the biology of myeloma. For example, gene expression profiling is already making a contribution to enhanced understanding of the biology of the disease whilst Next Generation Sequencing has revealed great genomic complexity and heterogeneity. Pathways involved in the oncogenesis, proliferation of the tumour and its resistance to apoptosis are being unravelled. Furthermore, knowledge of the tumour cell surface and its interactions with bystander cells and the bone marrow stroma enhance this understanding and provide novel targets for cell and antibody-based therapies. This review will discuss the development in understanding of the biology of the tumour cell and its environment in the bone marrow, the implementation of new therapeutic options contributing to significantly improved outcomes, and the progression towards more personalised medicine in this disorder.

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Proteomic Analysis for Finding Serum Pathogenic Factors and Potential Biomarkers in Multiple Myeloma

Cited by 25 publications

References 24 publications

Identification of potential cervical cancer serum biomarkers in Thai patients

Identification of potential cervical cancer serum biomarkers in Thai patients

Identification of High Serum Apolipoprotein A1 as a Favorable Prognostic Indicator in Patients with Multiple Myeloma

Towards Stratified Medicine in Plasma Cell Myeloma

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