Prognostic value of transglutaminase 2 in non-small cell lung cancer patients

Zhu, Chihong; Ling, Yutian; Danying, Wan; Jiang, Ruibin; Sheng, Huaying; Gu, Linhui; Jiang, Feng

doi:10.18632/oncotarget.17374

Cited by 12 publications

(8 citation statements)

References 30 publications

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“…Two independent studies of non‐small cell lung cancer patients show that elevated TG2 level predicts disease recurrence and shorter disease free survival, and suggest that TG2 level may be a prognostic marker of disease progression . Moreover, in chemotherapy patients, progression free survival is lengthened if the patients have low tumor levels of TG2 .…”

Section: Tg2 In Tumor Typesmentioning

confidence: 99%

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Eckert

2019

Molecular Carcinogenesis

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Transglutaminase 2 (TG2) has emerged as a key cancer cell survival factor that drives epithelial to mesenchymal transition, angiogenesis, metastasis, inflammation, drug resistance, cancer stem cell survival and stemness, and invasion and migration. TG2 can exist in a GTP‐bound signaling‐active conformation or in a transamidase‐active conformation. The GTP bound conformation of TG2 contributes to cell survival and the transamidase conformation can contribute to cell survival or death. We present evidence suggesting that TG2 has a role in human cancer, summarize what is known about the TG2 mechanism of action in a range of cancer types, and discuss TG2 as a cancer therapy target.

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Section: Tg2 In Tumor Typesmentioning

confidence: 99%

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Eckert

2019

Molecular Carcinogenesis

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“… 16 , 17 Role of TG2 expression in inflammation induced carcinogenesis is well established in various cancers including ovary, colorectal, breast, renal and lung. 8 , 10 - 13 Its role in GBC has not yet been studied. Our study, comprising 100 patients of GBC and 28 patients of cholelithiasis (control group) is the first study to evaluate expression of TG2 in a large cohort of GBC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Chihong et al 13 have demonstrated the role of TG2 in cell survival and cancer progression in 194 patients diagnosed with non-small cell lung cancer (NSCLC) and found that TG2 expression was significantly higher in lung cancer tissues as compared to paired marginal tissues or normal tissues. They also postulated that patients with low TG2 expression levels had longer disease free survival and overall survival as compared those with higher TG2 expression and also found that high TG2 expression correlated with NSCLC recurrence.…”

Section: Discussionmentioning

confidence: 99%

“… 9 Role of TG2 in cancer progression has been studied in various cancers including ovary, 8 colorectal, 10 breast, 11 renal 12 and lung. 13 These studies showed that high TG2 expression group had poorer overall survival rate than those in the low expression group. We aim to analyze the expression of TG2 in GBC and its role as potential prognostic marker, a first of its kind study.…”

Section: Introductionmentioning

confidence: 97%

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Study of tumor transglutaminase 2 expression in gallbladder cancer – Is it a novel predictor of survival?

Gupta

Garg

Kumar

et al. 2020

Ann Hepatobiliary Pancreat Surg

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Backgrounds/Aims Transglutaminase 2 (TG2) is known to be an important mediator of inflammation induced carcinogenesis pathway. Chronic inflammation is the most important causative factor in Gallbladder cancer (GBC) carcinogenesis. We analyzed the expression of TG2 in GBC and its role as potential prognostic marker, first of its kind study. Methods We analyzed TG2 expression in 100 cases of GBC and 28 cases of non-cancer gallbladder specimen (calculus cholecystitis). We studied TG2 expression in GBC in comparison to control group and evaluated its role as a potential prognostic marker. Results TG2 score (1-9) was calculated by multiplying percentage cytoplasmic expression (P) with intensity of expression (I) in tumor cells. Positive TG-2 expression was observed in 62% of GBC patients compared to only 21% (n=6) in control group ( p =0.001). In curative resection subgroup (n=54), TG2 positive patients showed shorter disease free survival rate ( p =0.04) and higher rate of recurrence ( p =0.03) compared to TG2 negative patients. TG2 positive expression was observed in 15/16 of patients with recurrent disease. In palliative treatment subgroup, patients with strong TG2 positive expression had poorer disease specific survival ( p =0.01) as compared to weakly positive group. On multivariate analysis, lymph node status ( p =0.03) and TG2 expression ( p =0.037), were found to be significant predictor of recurrence and eventual survival. Conclusions Positive TG2 expression was related to higher recurrence rates post curative surgery, shorter disease free and overall survival and ultimately portended poor prognosis. It may be helpful in better prognostication and tailoring therapeutic approach for better management of GBC.

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“…These sections were then prepared for antigen retrieval in a citrate buffer with a pH of 6.0 by heating them in a microwave for 5-min cycles. The sections were then incubated overnight at a temperature of 4°C with a 1:200 diluted Anti-TG2 antibody (Abcam, USA), after which we incubated them with biotinlabeled Rabbit Anti-Mouse IgG H&L preabsorbed (Abcam, USA) for immunostaining (Chihong, et al, 2017).…”

Section: Lung Tissue Immunohistochemistrymentioning

confidence: 99%

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

et al. 2020

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Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps take up Ca2+ from the cytoplasm to maintain the balance of intracellular Ca2+. A decline in expression or activity of SERCA results in persistent store-operated calcium entry (SOCE). In cardiomyocytes as well as vascular smooth muscle cells (SMCs), SERCA2 acts as an important regulator of calcium cycling. The purpose of this study is to identify and better understand the role of transglutaminases2 (TG2) as a key factor involved in SERCA2 serotonination (s-SERCA2) and to elucidate the underlying mechanism of action. Human pulmonary venous smooth muscle cell in normal pulmonary lobe were isolated and cultured in vitro. Establishment of hypoxic pulmonary hypertension model in wild type and TG2 knockout mice. SERCA2 serotonylation was analyzed by co-(immunoprecipitation) IP when the TG2 gene silenced or overexpressed under normoxia and hypoxia in vivo and in vitro. Intracellular calcium ion was measured by using Fluo-4AM probe under normoxia and hypoxia. Real-time (RT)-PCR and Western blot analyzed expression of TG2, TRPC1, and TRPC6 under normoxia and hypoxia. Bioactivity of cells were analyzed by using Cell Counting Kit (CCK)-8, flow cytometry, wound healing, RT-PCR, and Western blot under PST-2744 and cyclopiazonic acid. We confirmed that 1) hypoxia enhanced the expression and activity of TG2, and 2) hypoxia increased the basal intracellular Ca2+ concentration ([Ca2+]i) and SOCE through activating TRPC6 on human pulmonary vein smooth muscle cells (hPVSMC). Then, we investigated the effects of overexpression and downregulation of the TG2 gene on the activity of SERCA2, s-SERCA2, basal [Ca2+]i, and SOCE under normoxia and hypoxia in vitro, and investigated the activity of SERCA2 and s-SERCA2 in vivo, respectively. We confirmed that SERCA2 serotonylation inhibited the activity of SERCA2 and increased the Ca2+ influx, and that hypoxia induced TG2-mediated SERCA2 serotonylation both in vivo and in vitro. Furthermore, we investigated the effect of TG2 activity on the biological behavior of hPVSMC by using an inhibitor and agonist of SERCA2, respectively. Finally, we confirmed that chronic hypoxia cannot increase vessel wall thickness, the right ventricular systolic pressure (RVSP), and right ventricular hypertrophy index (RVHI) of vascular smooth muscle-specific Tgm2−/− mice. These results indicated that hypoxia promoted TG2-mediated SERCA2 serotonylation, thereby leading to inhibition of SERCA2 activity, which further increased the calcium influx through the TRPC6

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Prognostic value of transglutaminase 2 in non-small cell lung cancer patients

Cited by 12 publications

References 30 publications

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target

Study of tumor transglutaminase 2 expression in gallbladder cancer – Is it a novel predictor of survival?

Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling

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