Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells

Gao, Song; Pan, Yan; Song, Libin; Dong, Lei; Weng, Lao I.; Wang, Peng; Hua, Yi-Jun; Chen, Zheng; Liu, Luming

doi:10.1155/2016/7028289

Cited by 7 publications

(6 citation statements)

References 18 publications

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“…Four studies evaluated non-small cell lung cancer (NSCLC), 5 , 32 – 34 four evaluated gastric cancer (GC), 9 , 26 , 27 , 38 and five evaluated OSCC; 8 , 15 , 28 , 29 , 36 breast cancer, 6 , 30 , 31 hepatocellular carcinoma (HCC), 7 , 25 , 39 and ovarian cancer (OC) 13 , 21 , 22 were each evaluated in three studies. Esophageal squamous cell carcinoma (ESCC), 10 , 23 colorectal cancer (CRC), 11 , 16 and pancreatic cancer (PC) 12 , 24 were each evaluated in two studies. Nasopharyngeal carcinoma (NPC), 14 astrocytoma, 20 cervical cancer (CC), 37 tongue squamous cell carcinoma (TSCC), 35 and mucoepidermoid carcinoma (MEC) 19 were each evaluated in one study.…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of NANOG expression in solid tumors: a meta-analysis

Zhao¹,

Liu²,

Chen³

et al. 2018

OTT

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PurposeNANOG is a tumor marker and indicates poor prognosis in various neoplasms; however, the evidence is controversial. This meta-analysis investigated the association of NANOG expression and clinicopathological features, and it impact on survival of patients with malignant tumors.MethodsStudies published through May 31, 2018 were retrieved from PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure. Two researchers independently screened the content and quality of studies and extracted data. Correlations of NANOG expression, clinicopathological variables, and survival were analyzed and the combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated.ResultsThirty-three articles including 35 data sets of 3,959 patients were analyzed. Overall, elevated NANOG expression was associated with poor overall survival (HR = 2.19; 95% CI: 1.87–2.58, P<0.001) and poor disease-free survival (HR = 2.21, 95% CI: 1.54–3.18, P<0.001). Subgroup analysis found that NANOG expression was associated with worse overall survival in non–small cell lung (HR = 1.87; 95% CI: 1.26–2.76, P = 0.002), head and neck (HR = 2.29; 95% CI: 1.75–3.02, P<0.001), and digestive system (HR = 2.38; 95% CI: 1.95–2.91, P<0.001) cancers. Moreover, we found that high NANOG expression was associated with poor tumor differentiation (OR = 2.63; 95% CI: 1.59–4.55, P = 0.001), lymph node metastasis (OR = 2.59; 95% CI: 1.50–4.47, P = 0.001), advanced TNM stage (OR = 2.22; 95% CI: 1.42–3.45, P<0.001), and T stage (OR = 0.44; 95% CI: 0.20–0.93, P = 0.031).ConclusionThe evidence supports NANOG as a tumor biomarker to guide clinical management and indicate prognosis. Additional studies are needed to further validate these results.

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Section: Resultsmentioning

confidence: 99%

Prognostic significance of NANOG expression in solid tumors: a meta-analysis

Zhao¹,

Liu²,

Chen³

et al. 2018

OTT

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“…NANOG protein was expressed in 81% of cancer tissue; expression was strong in 26%, moderate in 32%, weak in 23% and it was absent in 19% of samples. 60 NANOG might thus be associated with the early stages of pancreatic cancer and might be used as a potential prognostic marker. 58,59…”

Section: Nanog In Cancermentioning

confidence: 99%

NANOG expression in human development and cancerogenesis

Grubelnik

Boštjančič

Pavlič

et al. 2020

Exp Biol Med (Maywood)

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NANOG is an important stem cell transcription factor involved in human development and cancerogenesis. Its expression is complex and regulated on different levels. Moreover, NANOG protein might regulate hundreds of target genes at the same time. NANOG is crucial for preimplantation development phase and progressively decreases during embryonic stem cells differentiation, thus regulating embryonic and fetal development. Postnatally, NANOG is undetectable or expressed in very low amounts in the majority of human tissues. NANOG re-expression can be detected during cancerogenesis, already in precancerous lesions, with increasing levels of NANOG in high grade dysplasia. NANOG is believed to enable cancer cells to obtain stem-cell like properties, which are believed to be the source of expanding growth, tumor maintenance, metastasis formation, and tumor relapse. High NANOG expression in cancer is frequently associated with advanced stage, poor differentiation, worse overall survival, and resistance to treatment, and is therefore a promising prognostic and predictive marker. We summarize the current knowledge on the role of NANOG in cancerogenesis and development, including our own experience. We provide a critical overview of NANOG as a prognostic and diagnostic factor, including problems regarding its regulation and detection. Impact statement NANOG has emerged as a key stem cell transcription factor in normal development and cancerogenesis. It is generally regarded as a good prognostic and predictive factor in various human cancers. It is less known that it is expressed already at precancerous stages in various organs, suggesting that finally an ideal candidate diagnostic marker has been discovered, enabling to distinguish between true dysplasia and reactive atypia. NANOG regulation is complex, and new insights into our understanding of its regulation might provide important information for future development in a broad field of two entirely different processes, i.e. normal development and cancerogenesis, showing how a physiologic mechanism can be used and abused, transforming itself into a key mechanism of disease development and progression.

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“…It consists of four exons and three introns, and encodes 305 amino acids. It is the key genes for stem cells on maintain self-proliferation and multidirectional differentiation [34–36]. With the development of research, NANOG has been found highly expression in breast cancer, spermatogonioma, gastric cancer, intestinal cancer, cervical cancer, oral squamous cell cancer and pancreatic cancer, and so on.…”

Section: Discussionmentioning

confidence: 99%

Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals

Chen

Wang

2019

Bioscience Reports

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To investigate the possible mechanism of Qingyihuaji formula (QYHJ) for reversing gemcitabine (GEM) resistant human pancreatic cancer. Cell proliferation, apoptosis, migration and invasion were detected in CFPAC-1 cells. Xenograft mice established with CFPAC-1 through subcutaneous on 33 immunodeficient nude mice and randomly divided into four groups: vehicle, GEM (35 mg/kg), QYHJ (40 g/kg), and GEM + QYHJ (35 mg/kg + 40 g/kg) groups for 28-day treatment. Tumor growth and the mRNA expression of lncRNA AB209630, miR373, EphB2, and NANOG evaluated in dissected tumor tissue by real-time PCR, the CD133+ cancer stem cells were isolated by flow cytometer, and the changes of the tumor sphere forming were measured. QYHJ, especially the combination of GEM and QYHJ, was significantly inhibited the cell proliferation and migration of CFPAC-1 in vitro in the indicated times. The combination of GEM and QYHJ also remarkably promoted the cell apoptosis of CFPAC-1. QYHJ treatment effectively blocked the tumor growth in nude mice. QYHJ, especially GEM + QYHJ treatment, was significantly increased the mRNA expression of lncRNA AB209630, significantly decreased the mRNA levels of miR373, EphB2 and NANOG, and markedly reduced the tumor sphere formation and the numbers of CD133+ stem cells. In addition, GEM alone treatment had no significant effect in the above biomarker changes. QYHJ could effectivly enhance the antihuman pancreatic tumor activity of GEM, which may be through inhibiting pancreatic cancer stem cell differentiation by lncRNA AB209630/miR-373/EphB2-NANOG signaling pathway.

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Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells

Cited by 7 publications

References 18 publications

Prognostic significance of NANOG expression in solid tumors: a meta-analysis

Prognostic significance of NANOG expression in solid tumors: a meta-analysis

NANOG expression in human development and cancerogenesis

Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals

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