Serum HMGB1 as a Diagnostic Marker for Malignant Peritoneal Mesothelioma

Tabata, Chiharu; Kanemura, Shingo; Tabata, Rie; Masachika, Eriko; Shibata, Eisuke; Otsuki, Taiichiro; Nishizaki, Tomoyuki; Nakano, Takashi

doi:10.1097/mcg.0b013e318297fa65

Cited by 32 publications

(24 citation statements)

References 36 publications

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“…Consistently, we found that HMGB1 levels in serum and plasma were higher in MM patients compared to healthy individuals (Figure 1) (78) and these findings were confirmed by other studies reporting significantly higher serum HMGB1 levels in MM patients compared to individuals with benign asbestos-related diseases (79,80). A systematic review and meta-analysis established HMGB1 as a prognostic marker for MM (79,81).…”

Section: High Mobility Group Box 1 Protein (Hmgb1)supporting

confidence: 79%

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Chen

Gaudino

Pass

et al. 2017

Transl. Lung Cancer Res.

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Malignant mesothelioma (MM) is an aggressive and lethal cancer, mostly related to inhalation of asbestos and erionite fibers. MM is associated with poor prognosis, because of its resistance to current therapies, even if higher survival occurs in patients diagnosed and treated when at stage I of the disease.However, these do not exceed 5% of the total number of cases, due to the inadequacy of the existing biomarkers for early and accurate diagnosis. Therefore, new effective biomarkers are needed for MM detection at earlier stages and to develop tailored therapies. Here we review the most promising biomarkers in MM to date: mesothelin, soluble mesothelin-related peptides (SMRPs), megakaryocyte potentiating factor (MPF), Osteopontin (OPN), Fibulin-3, high mobility group B1 (HMGB1), microRNAs (miRNAs), multiplex protein signatures. The validation of these biomarkers will allow their use, alone or in combination, for monitoring individuals from cohorts at risk of MM and attaining early detection of MM that is instrumental in improving patient survival.

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Section: High Mobility Group Box 1 Protein (Hmgb1)supporting

confidence: 79%

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Chen

Gaudino

Pass

et al. 2017

Transl. Lung Cancer Res.

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“…One group from the USA provided the first evidence that HMGB1 was highly expressed in both tissues and sera of mesothelioma patients [20]. In a following report with similar results based on the exposure of Japanese subjects to asbestos, the HMGB1 protein levels in the sera from patients with diffuse malignant peritoneal mesothelioma were also reported to be significantly higher than those of nonmesothelioma subjects with a history of exposure to asbestos [21]. Serum HMGB1 was also a prognostic marker for Japanese patients with malignant pleural mesothelioma (MPM) [22].…”

Section: Introductionmentioning

confidence: 94%

Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases

Ying

Jiang

et al. 2017

Disease Markers

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High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine and is one of the most intriguing molecules in inflammatory disorders and cancers. Notably, HMGB1 is a potential therapeutic target and novel biomarker in related diseases. However, the diagnostic value of HMGB1 for benign and malignant asbestos-related diseases (ARDs) remains unclear. In this work, we detected preoperative serum HMGB1 levels in Chinese asbestos-exposed (AE) and ARDs populations and further evaluated the diagnostic value of HMGB1 in patients with certain types of ARDs, including those with pleural plaques, asbestosis, or malignant mesothelioma (MM). The experimental data presented that the serum level of HMGB1 was significantly elevated in AE and ARDs subjects. Our findings indicated that serum HMGB1 is a sensitive and specific biomarker for discriminating asbestosis- and MM-affected individuals from healthy or AE individuals. In addition, serum matrix metalloproteinases 2 and 9 are not correlated with HMGB1 in ARDs. Thus, our study provides supporting evidence for HMGB1 as a potential biomarker either for the clinical diagnosis of high-risk AE cohorts or for evaluating ARDs.

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“…44,45 Increased circulating HMGB1 is found in some cancers, including malignant peritoneal mesothelioma 46 and myelodysplastic syndromes. 20 Higher circulating HMGB1 is associated with worse clinical outcomes, and plasma samples with higher concentrations of HMGB1 (.150 ng/mL) in our study were from relapsed or progressive CLL patients and are correlated with .…”

Section: Org Frommentioning

confidence: 99%

Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia

Clear

Liu

et al. 2014

Blood

102

104

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Key Points• HMGB1 and DNA released from CLL cells induce nurse-like cell differentiation.• This differentiation appears TLR9/RAGE dependent.Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1. (Blood. 2014;123(11):1709-1719 IntroductionMany cancers arise from sites of infection, chronic irritation, and inflammation. An inflammatory microenvironment is an important participant in the neoplastic process, fostering proliferation, survival, and migration for cancers, including chronic lymphocytic leukemia (CLL).1-4 Stressed, injured, or dying cells release damage-associated molecular patterns (DAMPs), which initiate noninfectious inflammatory responses. [5][6][7] The DAMP high-mobility group protein B1 (HMGB1) is a major player associating inflammation and cancer. 8,9 HMGB1 is a nuclear protein that can be released passively by damaged or dead cells or actively by immune cells and stressed cancer cells. [10][11][12][13][14] HMGB1 regulates transcription factors but also behaves as a proinflammatory cytokine mediating inflammation. 13,[15][16][17][18] Nonprotein DAMPs, including DNA, RNA, and ATP, are also released by damaged or dying cells. 6,7,19 DAMPs are associated with acute inflammatory responses, chronic inflammation, and wound healing, but are also important components of the disordered tumor microenvironment. 8,20 HMGB1 is a DNA-binding protein, and increased serum concentrations of the HMGB1-DNA complex can activate the immune system and cause systemic autoimmune disease via the receptor for advanced glycation end products (RAGE) and toll-like receptor-9 (TLR9). 21 Interactions of HMGB1-RAGE-TLR9 constitute a tripod that triggers nuclear factor kB (NF-kB) activation 22 and promotes ...

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Serum HMGB1 as a Diagnostic Marker for Malignant Peritoneal Mesothelioma

Abstract: Our data suggest that serum HMGB1 concentration is a useful serum marker for DMPM.

Cited by 32 publications

References 36 publications

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

Serum HMGB1 as a Potential Biomarker for Patients with Asbestos-Related Diseases

Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia

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