Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker

Choe, Hun Jee; Kim, Jin Won; Han, Song Hee; Lee, Ju Hyun; Ahn, Sang Hoon; Park, Do Joong; Kim, Ji Won; Kim, Yu Jung; Lee, Hye Seung; Kim, Jee Hyun; Kim, Hyung‐Ho; Lee, Moon Hyoung

doi:10.3390/cancers12010086

Cited by 13 publications

(17 citation statements)

References 26 publications

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“…In addition, CACNA1D was found to be expressed on pancreatic islets and play a vital role in insulin secretion, which is involved in β-cell physiology and pathophysiology 31 , and AP1M2 expression was found to be upregulated only in pancreatic cancer 32 . Other genes, such as CCDC148 33 , SH3RF2 34 , VGLL1 35 and NET1 36 , were found to regulate different cell behaviors (such as cell proliferation and migration, cell death and cell cycle) involved in the development and progression of gastric cancer, whereas POLD3 was reported to be required for cell cycle progression and DNA synthesis and to be responsible for the high frequency of genomic duplications in human cancers 37 . No study was found on role of C4orf19 in cancers.…”

Section: Discussionmentioning

confidence: 99%

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

Wei

Zhou

Zhao

et al. 2021

Sci Rep

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To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75–3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31–2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38–2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11–2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14–3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02–3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis.

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Section: Discussionmentioning

confidence: 99%

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

Wei

Zhou

Zhao

et al. 2021

Sci Rep

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“…Cooperation of RTEF-1, as a downstream effector of the Hippo-YAP/TAZ pathway, with transcription factors is a common cellular phenomenon. RTEF-1 was reported to be regulated by PI3K/AKT/β-catenin signaling, which activated the transcription of MMP9, a key molecule that promotes gastric cancer cell proliferation and metastasis [ 23 ]. Furthermore, specific activator or inhibitor of Wnt/β-catenin signaling used in RTEF-1 overexpressed or siRNA VSMCs, respectively, has further suggested that Wnt/β-catenin signaling was involved in the anti-calcifying effect of RTEF-1.…”

Section: Discussionmentioning

confidence: 99%

RTEF-1 Inhibits Vascular Smooth Muscle Cell Calcification through Regulating Wnt/β-Catenin Signaling Pathway

et al. 2021

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Vascular calcification (VC) is highly prevailing in cardiovascular disease, diabetes mellitus, and chronic kidney disease and, when present, is associated with cardiovascular events and mortality. The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is regarded as the foundation for mediating VC. Related transcriptional enhancer factor (RTEF-1), also named as transcriptional enhanced associate domain (TEAD) 4 or transcriptional enhancer factor-3 (TEF-3), is a nuclear transcriptional factor with a potent effect on cardiovascular diseases, apart from its oncogenic role in the canonical Hippo pathway. However, the role and mechanism of RTEF-1 in VC, particularly in calcification of VSMCs, are poorly understood. Our results showed that RTEF-1 was reduced in calcified VSMCs. RTEF-1 significantly ameliorated β-glycerophosphate (β-GP)-induced VSMCs calcification, as detected by alizarin red staining and calcium content assay. Also, RTEF-1 reduced alkaline phosphatase (ALP) activity and decreased expressions of osteoblast markers such as Osteocalcin and Runt-related transcription factor-2 (Runx2), but increased expression of contractile protein, including SM α-actin (α-SMA). Additionally, RTEF-1 inhibited β-GP-activated Wnt/β-catenin pathway which plays a critical role in calcification and osteogenic differentiation of VSMCs. Specifically, RTEF-1 reduced the levels of Wnt3a, p-β-catenin (Ser675), glycogen synthase kinase-3β (GSK-3β), and p-GSK-3β (Ser9), but increased the levels of p-β-catenin (Ser33/37). Also, RTEF-1 increased the ratio of p-β-catenin (Ser33/37) to β-catenin proteins and decreased the ratio of p-GSK-3β (Ser9) to GSK-3β protein. LiCl, a Wnt/β-catenin signaling activator, was observed to reverse the protective effect of RTEF-1 overexpression on VSMCs calcification induced by β-GP. Accordingly, Dickkopf-1 (Dkk1), a Wnt antagonist, attenuated the role of RTEF-1 deficiency in β-GP-induced VSMCs calcification. Taken together, we concluded that RTEF-1 ameliorated β-GP-induced calcification and osteoblastic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling pathway.

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“…However, a tumor suppressor role of USP9X has been documented in pancreatic, colorectal, and renal cancer. The various substrates of USP9X are responsible for its complex role [ 17 - 19 ]. More importantly, the clinical significance and the biological roles of USP9X in cholangiocarcinoma remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bβ via deubiquitinating EGLN3

et al. 2021

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Background Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades. Cholangiocarcinoma silent nature limits early diagnosis and prevents efficient treatment. Methods Immunoblotting and immunohistochemistry were used to assess the expression profiling of USP9X and EGLN3 in cholangiocarcinoma patients. ShRNA was used to silence gene expression. Cell apoptosis, cell cycle, CCK8, clone formation, shRNA interference and xenograft mouse model were used to explore biological function of USP9X and EGLN3. The underlying molecular mechanism of USP9X in cholangiocarcinoma was determined by immunoblotting, co-immunoprecipitation and quantitative real time PCR (qPCR). Results Here we demonstrated that USP9X is downregulated in cholangiocarcinoma which contributes to tumorigenesis. The expression of USP9X in cholangiocarcinoma inhibited cell proliferation and colony formation in vitro as well as xenograft tumorigenicity in vivo. Clinical data demonstrated that expression levels of USP9X were positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that USP9X was involved in the deubiquitination of EGLN3, a member of 2-oxoglutarate and iron-dependent dioxygenases. USP9X elicited tumor suppressor role by preventing degradation of EGLN3. Importantly, knockdown of EGLN3 impaired USP9X-mediated suppression of proliferation. USP9X positively regulated the expression level of apoptosis pathway genes de through EGLN3 thus involved in apoptosis of cholangiocarcinoma. Conclusion These findings help to understand that USP9X alleviates the malignant potential of cholangiocarcinoma through upregulation of EGLN3. Consequently, we provide novel insight into that USP9X is a potential biomarker or serves as a therapeutic or diagnostic target for cholangiocarcinoma.

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Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker

Cited by 13 publications

References 26 publications

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients

RTEF-1 Inhibits Vascular Smooth Muscle Cell Calcification through Regulating Wnt/β-Catenin Signaling Pathway

USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bβ via deubiquitinating EGLN3

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