A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

Cao, Hongxin; Zhang, Shiyi; Shen, Jian; Wu, Zhi‐Yong; Wu, Jian‐Yi; Wang, Shaohong; Li, En‐Min; Xu, Li‐Yan

doi:10.18632/oncotarget.3102

Cited by 40 publications

(41 citation statements)

References 42 publications

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“…For example, it is obvious from the network that myosin-9 (MYH9), plastin-3 (PLS3) and transgelin-2 (TAGLN2) are linked together because all of the three proteins are involved in actin binding and cell motility. Previous studies showed that MYH9 promotes cancer cell migration and invasion and were up regulated in non-small cell lung cancer (NSCLC)12 and esophageal squamous cell carcinoma (ESCC)13. PLS3 has been identified as a novel marker for circulating tumor cells in colorectal cancer (CRC)14.…”

Section: Resultsmentioning

confidence: 99%

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

Wang

Zhi

Liu

et al. 2016

Sci Rep

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The aim of this study was to identify biomarkers for gastric cancer (GC) by iTRAQ. Using proteins extracted from a panel of 4 pairs of gastric adenocarcinoma samples (stage III-IV, Her-2 negative), we identified 10 up regulated and 9 down regulated proteins in all four pairs of GC samples compared to adjacent normal gastric tissue. The up regulated proteins are mainly involved in cell motility, while the down regulated proteins are mitochondrial enzymes involved in energy metabolism. The expression of three up regulated proteins (ANXA1, NNMT, fibulin-5) and one of the down regulated proteins (UQCRC1) was validated by Western Blot in 97 GC samples. ANXA1 was up regulated in 61.36% of stage I/II GC samples compared to matched adjacent normal gastric tissue, and its expression increased further in stage III/IV samples. Knockdown of ANXA1 by siRNA significantly inhibited GC cell migration and invasion, whereas over expression of ANXA1 promoted migration and invasion. We found decreased expression of UQCRC1 in all stages of GC samples. Our data suggest that increased cell motility and decreased mitochondrial energy metabolism are important hallmarks during the development of GC.

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Section: Resultsmentioning

confidence: 99%

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

Wang

Zhi

Liu

et al. 2016

Sci Rep

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“…In a study by Cao et al. , Annexin II, kindlin 2, and myosin 9 were proved to be abnormally expressed in ESCC samples and could be significant predictors of ESCC OS. Additionally, transglutaminase 3 expression was validated in 76 primary tumor samples by IHC and found to be inversely correlated with shorter disease‐specific survival rate .…”

Section: Discussionmentioning

confidence: 96%

“…Du et al [24] found that there were 22 dysregulated proteins in ESCCs compared to tumor-adjacent normal tissues and that the up-regulated expression of calreticulin and a 78 kDa glucose-regulated protein were involved in poor prognosis through proteomic profiling. In a study by Cao et al [25], Annexin II, kindlin 2, and myosin 9 were proved to be abnormally expressed in ESCC samples and could be significant predictors of ESCC OS.…”

Section: Groupmentioning

confidence: 95%

Tissue‐based quantitative proteomics to screen and identify the potential biomarkers for early recurrence/metastasis of esophageal squamous cell carcinoma

et al. 2018

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Esophageal squamous cell carcinoma (ESCC) is the eighth cause of cancer‐related deaths worldwide. To screen potential biomarkers associated with early recurrence/metastasis (R/M) of ESCC patients after radical resection, ESCC patients were analyzed by a comparative proteomics analysis using iTRAQ with RPLC‐MS to screen differential proteins among R/M groups and adjacent normal tissues. The proteins were identified by qRT‐PCR, Western blotting, and tissue microarray. The protein and mRNA expression difference of PHB2 between tumor tissues of ESCC patients and adjacent normal tissues, ESCC patients with and without metastasis, four ESCC cell lines and normal esophageal epithelial cells were inspected using immunohistochemical staining, qRT‐PCR, and Western blotting. The EC109 and TE1 cells were used to establish PHB2 knockdown cell models, and their cell proliferation and invasion ability were determined by cell counting method, Transwell® assay. Thirteen proteins were selected by cutoff value of 0.67 fold for underexpression and 1.5‐fold for overexpression. Seven proteins were confirmed to be associated with R/M among the 13 proteins. The potential biomarker PHB2 for early recurrence/metastasis of ESCC was identified. PHB2 expression was related to the OS of ESCC patients (P = 0.032) and had high levels in the tumor tissues and human cell lines of ESCC (P = 0.0002). Also, the high PHB2 expression promoted the metastasis of ESCC (P = 0.0075), suggesting high PHB2 expression was a potential prognostic biomarker. Experiments showed that PHB2 could significantly promote the proliferation and cell invasion ability of human ESCC cell lines and the knockdown of PHB2 suppressed the phosphorylation level of AKT, as well as the expression of MMP9 and RAC1. PHB2 could predict the early metastasis of ESCC patients.

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“…141 In addition to MDM2, KDM4C activates two additional high-risk genes PPARG and NANOG) in ESCC tumors. 142 The presence of this 3-gene signature is a strong independent predictor of lower OS.…”

Section: Esophageal Squamous Cell Carcinoma (Escc)mentioning

confidence: 98%

Advances in histone demethylase KDM4 as cancer therapeutic targets

et al. 2020

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The KDM4 subfamily H3K9 histone demethylases are epigenetic regulators that control chromatin structure and gene expression by demethylating histone H3K9, H3K36, and H1.4K26. The KDM4 subfamily mainly consists of four proteins (KDM4A‐D), all harboring the Jumonji C domain (JmjC) but with differential substrate specificities. KDM4A‐C proteins also possess the double PHD and Tudor domains, whereas KDM4D lacks these domains. KDM4 proteins are overexpressed or deregulated in multiple cancers, cardiovascular diseases, and mental retardation and are thus potential therapeutic targets. Despite extensive efforts, however, there are very few KDM4‐selective inhibitors. Defining the exact physiological and oncogenic functions of KDM4 demethylase will provide the foundation for the discovery of novel potent inhibitors. In this review, we focus on recent studies highlighting the oncogenic functions of KDM4s and the interplay between KDM4‐mediated epigenetic and metabolic pathways in cancer. We also review currently available KDM4 inhibitors and discuss their potential as therapeutic agents for cancer treatment.

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A three-protein signature and clinical outcome in esophageal squamous cell carcinoma

Cited by 40 publications

References 42 publications

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

Tissue‐based quantitative proteomics to screen and identify the potential biomarkers for early recurrence/metastasis of esophageal squamous cell carcinoma

Advances in histone demethylase KDM4 as cancer therapeutic targets

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