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1.
S100 family members: potential therapeutic target in patients with hepatocellular carcinoma: A STROBE study.
Zhang, C, Yao, R, Chen, J, Zou, Q, Zeng, L
Medicine. 2021;(3):e24135
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Abstract
Proteins in S100 family exhibit different expressions patterns and perform different cytological functions, playing substantial roles in certain cancers, carcinogenesis, and disease progression. However, the expression and role of S100 family members in the prognosis of hepatocellular carcinoma (HCC) remains unclear. To investigate the effect of S100 family members for the prognosis of liver cancer, we assessed overall survival (OS) using a Kaplan-Meier plotter (KM plotter) in liver cancer patients with different situation. Our results showed that 15 members of the S100 family exhibited high levels of expression and these levels were correlated with OS in liver cancer patients. The higher expression of S100A5, S100A7, S100A7A, S100A12, S100Z, and S100G was reflected with better survival in liver cancer patients. However, worse prognosis was related to higher levels of expression of S100A2, S100A6, S100A8, S100A9, S100A10, S100A11, S10013, S100A14, and S100P. We then evaluated the prognostic values of S100 family members expression for evaluating different stages of AJCC-T, vascular invasion, alcohol consumption, and the presence of hepatitis virus in liver cancer patients. Lastly, we studied the prognostic values of S100 family members expression for patients after sorafenib treatment. In conclusion, our findings show that the proteins of S100 family members exhibit differential expression and may be useful as targets for liver cancer, facilitating novel diagnostic and therapeutic strategies in cancer.
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Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer.
Guo, AJ, Wang, FJ, Ji, Q, Geng, HW, Yan, X, Wang, LQ, Tie, WW, Liu, XY, Thorne, RF, Liu, G, et al
Proteomics. Clinical applications. 2021;(1):e2000056
Abstract
PURPOSE The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. EXPERIMENTAL DESIGN Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. RESULTS Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. CONCLUSIONS AND CLINICAL RELEVANCE The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.
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The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins.
Bharadwaj, A, Kempster, E, Waisman, DM
Biomolecules. 2021;(12)
Abstract
Mutualistic symbiosis refers to the symbiotic relationship between individuals of different species in which both individuals benefit from the association. S100A10, a member of the S100 family of Ca2+-binding proteins, exists as a tight dimer and binds two annexin A2 molecules. This association forms the annexin A2/S100A10 complex known as AIIt, and modifies the distinct functions of both proteins. Annexin A2 is a Ca2+-binding protein that binds F-actin, phospholipid, RNA, and specific polysaccharides such as heparin. S100A10 does not bind Ca2+, but binds tPA, plasminogen, certain plasma membrane ion channels, neurotransmitter receptors, and the structural scaffold protein, AHNAK. S100A10 relies on annexin A2 for its intracellular survival: in the absence of annexin A2, it is rapidly destroyed by ubiquitin-dependent and independent proteasomal degradation. Annexin A2 requires S100A10 to increase its affinity for Ca2+, facilitating its participation in Ca2+-dependent processes such as membrane binding. S100A10 binds tissue plasminogen activator and plasminogen, and promotes plasminogen activation to plasmin, which is a process stimulated by annexin A2. In contrast, annexin A2 acts as a plasmin reductase and facilitates the autoproteolytic destruction of plasmin. This review examines the relationship between annexin A2 and S100A10, and how their mutualistic symbiosis affects the function of both proteins.
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The Role of CK7, S100A1, and CD82 (KAI1) Expression in the Differential Diagnosis of Chromophobe Renal Cell Carcinoma and Renal Oncocytoma.
Sari, ZB, Açikalin, MF, Arik, D, Özen, A, Can, C, Çolak, E
Applied immunohistochemistry & molecular morphology : AIMM. 2021;(7):534-540
Abstract
Renal oncocytoma is a benign renal tumor originated from intercalated cells of collecting ducts like chromophobe renal cell carcinoma (RCC). The differential diagnosis of these 2 tumors is important because while they are histologically and cytologically similar, they show different biological behavior. For the differential diagnosis, several immunohistochemical markers have been investigated. But, differential diagnostic challenges remain and the identification of additional markers is needed. Cytokeratin 7 (CK7) is one of ductal-type keratins, which is expressed in tumors of breast, pancreas, lung, thyroid, ovary, endometrium, urinary bladder, and the kidney. S100A1 is the first defined member of the calcium-binding S100 protein family and it organizes several cellular functions including cell cycle progression and cell differentiation.CD82 is a tetraspanin membrane protein, which functions as a metastasis supressor. In this study, we immunohistochemically investigated the expressions of CK7, S100A1, and CD82 in 30 chromophobe RCC (23 classic and 7 eosinophilic variant) and 19 oncocytomas. When these markers were evaluated separately and together, their expressions in chromophobe RCC and renal oncocytoma show statistically significant difference (P<0.001). Similar statistically significant results were also seen between eosinophilic chromophobe RCC and oncocytoma (P<0.001). For both classic and eosinophilic-variant chromophobe RCCs, CK7+/S100A1-/CD82+ profile being the most common. In oncocytomas, the most frequently observed profile was CK7-/S100A1+/CD82-. Our results showed that the application of a panel consisting of CK7, S100A1, and CD82 may provide accurate categorization of the tumors in difficult cases.
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Modulation of Ion Channels and Receptors by p11 (S100A10).
Seo, JS, Svenningsson, P
Trends in pharmacological sciences. 2020;(7):487-497
Abstract
p11 (S100A10, annexin II light chain, calpactin I light chain) is a multifunctional protein that forms a heterotetrameric complex with Annexin A2, particularly at cell membranes. p11, alone or together with Annexin A2, interacts with several ion channels and receptors and regulates their cellular localization and function. Altered levels of p11 are implicated in the pathophysiology of several forms of cancer, psychiatric disorders, and neurodegeneration. Via interactions with ion channels and receptors, p11 modulates therapeutic actions of drugs targeting brain disorders. By serving as a plasminogen receptor, p11 plays an important role in plasmin generation, fibrinolysis, angiogenesis, tumor progression, and metastasis. Here, we review mechanisms whereby p11 regulates functions of ion channels and receptors in health and disease states.
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The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients.
Gall, LS, Vulliamy, P, Gillespie, S, Jones, TF, Pierre, RSJ, Breukers, SE, Gaarder, C, Juffermans, NP, Maegele, M, Stensballe, J, et al
Annals of surgery. 2019;(6):1184-1191
Abstract
OBJECTIVE To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. METHODS A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. RESULTS Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. CONCLUSIONS Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.
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Association between serum S100A1 level and Global Registry of Acute Coronary Events score in patients with non-ST-segment elevation acute coronary syndrome.
Li, Y, Han, C, Zhang, P, Zang, W, Guo, R
The Journal of international medical research. 2018;(7):2670-2678
Abstract
Objective Acute coronary syndrome (ACS) is associated with several clinical syndromes, one of which is acute non-ST-segment ACS (NSTE-ACS). S100A1 is a calcium-dependent regulator of heart contraction and relaxation. We investigated the association between the serum S100A1 level and the Global Registry of Acute Coronary Events (GRACE) risk score in patients with NSTE-ACS and the potential of using the serum S100A1 level to predict the 30-day prognosis of NSTE-ACS. Methods The clinical characteristics of 162 patients with NSTE-ACS were analyzed to determine the GRACE score. The serum S100A1 concentration was determined using fasting antecubital venous blood. The patients were divided into different groups according to the serum S100A1 level, and the 30-day NSTE-ACS prognosis was evaluated using Kaplan-Meier analysis. Results The serum S100A1 levels differed significantly among the groups. Correlation analysis showed that the serum S100A1 level was positively correlated with the GRACE score. Kaplan-Meier analysis revealed that the number of 30-day cardiac events was significantly higher in patients with an S100A1 level of >3.41 ng/mL. Conclusions S100A1 is a potential biomarker that can predict the progression of NSTE-ACS and aid in its early risk stratification and prognosis.
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Neuron-specific enolase and S-100b in prolonged targeted temperature management after cardiac arrest: A randomised study.
Duez, CHV, Grejs, AM, Jeppesen, AN, Schrøder, AD, Søreide, E, Nielsen, JF, Kirkegaard, H
Resuscitation. 2018;:79-86
Abstract
BACKGROUND We aimed to investigate the impact of prolonged targeted temperature management (TTM) in cardiac arrest patients on release of serum levels of NSE and S-100b and their prognostic performances. METHODS This is a substudy of the Targeted Temperature Management for 24 vs 48h trial. NSE and S-100b levels were analysed retrospectively in serum samples collected upon admission, at 24, 48, and 72h after reaching the target temperature of 33±1°C. The primary outcome was biomarker serum concentrations and secondary outcome was the cerebral performance category score after 6 months. RESULTS 115 patients from two centres were analysed. NSE and S-100b levels did not differ between TTM groups at any single time-point. Poor outcome patients had higher biomarker levels at 24, 48, and 72h: NSE: 9.73 (7.2; 10.9) versus 20.40 (12.7; 27.2), 8.86 (6.6; 9.6) versus 17.47 (11.1; 37.3) and 6.23 (5.3; 8.5) versus 31.05 (12.8; 52.5) respectively and S-100b: 0.09 (0.07; 0.11) versus 0.23 (0.19; 0.39), 0.08 (0.07; 0.09) versus 0.18 (0.15; 0.33) and 0.07 (0.06; 0.08) versus 0.13 (0.09; 0.23). The daily changes in NSE from admission to Day 2 after the cardiac arrest (CA) were also related to the outcome (p=0.003 and p=0.02). The best prediction of outcome was found at 72h for NSE and at 24h as well as 48h for S100b. CONCLUSIONS No clinically relevant differences were found in the levels of NSE or S-100b between standard and prolonged TTM. Prognostic reliability of NSE and S-100b was unaltered by prolonged TTM.