Diverse roles of FOXO family members in gastric cancer

Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of E2F1/2/3/5/8 were significantly higher both in GC tissues and cell lines. The expression levels of E2F1 and E2F4 were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of E2F2, E2F5, E2F7 and E2F8 is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher E2F3 and E2F6 mRNA expression was found to increase GC patients’ OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs (E2F1/2/3/7/8). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together, E2F1/2/3/5/8 can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.

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Comprehensive Analysis and Identification of Prognostic Biomarkers and Therapeutic Targets Among FAM83 Family Members for Gastric Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.719613 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tianhao Zhang ◽

Shurong Lai ◽

Yuzhi Cai ◽

Zhixin Huang ◽

Ying Li ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Nk Cells ◽

Mutation Rate ◽

Poor Prognosis ◽

Prognostic Model ◽

Family Members ◽

High Expression ◽

Macrophage Cells ◽

Tumorigenesis And Progression

Background: Gastric cancer (GC) is one of the most common and poor prognosis malignancy in the world. The Family with sequence similarity 83 (FAM83) comprises of eight members of A–H. Accumulating evidence confirmed important roles for FAM83 family in tumorigenesis and progression. However, the prognostic values of FAM83 family in GC still have not been clarified.Methods: ONCOMINE, UALCAN, GEPIA, THE HUMAN PROTEIN ATLAS, Kaplan–Meier Plotter, cBioPortal, DAVID, STRING and TIMER databases and R software were adopted in this study.Results: In this study, we demonstrated that the mRNA levels of FAM83 B/C/D/H were significantly up-regulated in stomach adenocarcinoma (STAD), but the protein level of FAM83G/H were remarkable lowly in STAD. Next, FAM83C/D/G/H were significantly associated with tumor stages in STAD patients. Then, the mutation rate of FAM83 family members in STAD patients was 46%, and the highest mutation rate was FAM83H (23%). Furthermore, the functions of FAM83 family and their 259 co-expression genes were primarily related to Shigellosis, RNA degradation and Ribosome biogenesis in eukaryotes pathway. Besides, we have established the prognostic model of FAM83 family in STAD, including the prognostic model of STAD patients (FAM83C/D/G), STAD with lymph node metastasis (FAM83C/D/G/H) and STAD with ERBB2 high expression (FAM83G/H). FAM83C/D high expression with a poor prognosis, while FAM83G/H high expression with a favorable prognosis of STAD. Additionally, we found that the expression of FAM83C/D/G/H were significantly correlated with the infiltration of six types of immune cells [B cells, CD8+T cells, CD4+T cells, macrophages and Myeloid dendritic cells (DC)], whereas CD4+T cells and Macrophage cells have higher risk scores (HR > 1) when FAM83C lowly expression and FAM83D highly expression. The risk score of NK cells was significantly reduced when FAM83G lowly expression and FAM83H highly expression (HR < 1).Conclusion: These findings suggested that FAM83C/D/G/H might play key roles in STAD tumorigenesis and progression, and FAM83C/D might be risk factors but FAM83G/H might be favorable prognostic factors for STAD patients. In addition, CD4+T cells and Macrophage cells may be the promoters of FAM83D in progression of STAD, while NK cells may promote the protective effect of FAM83H on STAD patients.

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2215 Differential expression of CNN family members CYR61, CTGF and NOV in gastric cancer and association with disease progression

European Journal of Cancer ◽

10.1016/s0959-8049(16)31131-5 ◽

2015 ◽

Vol 51 ◽

pp. S404

Author(s):

X. Gao ◽

K. Ji ◽

Y. Jia ◽

J. Li ◽

J. Ji ◽

...

Keyword(s):

Gastric Cancer ◽

Disease Progression ◽

Differential Expression ◽

Family Members

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Tumor necrosis factor-α-induced apoptosis of gastric cancer MKN28 cells: Accelerated degradation of the inhibitor of apoptosis family members

Archives of Biochemistry and Biophysics ◽

10.1016/j.abb.2014.12.003 ◽

2015 ◽

Vol 566 ◽

pp. 43-48 ◽

Cited By ~ 5

Author(s):

Maki Kitagawa ◽

Atsushi Shiozaki ◽

Daisuke Ichikawa ◽

Shingo Nakashima ◽

Toshiyuki Kosuga ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Family Members ◽

Inhibitor Of Apoptosis ◽

Accelerated Degradation ◽

Induced Apoptosis ◽

Factor Α ◽

Necrosis Factor

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Prognostic values of E2F mRNA expression in human gastric cancer

Bioscience Reports ◽

10.1042/bsr20181264 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 12

Author(s):

Theasha Manicum ◽

Fubiao Ni ◽

Yiming Ye ◽

Xuhui Fan ◽

Bi-Cheng Chen

Keyword(s):

Gastric Cancer ◽

Transcription Factors ◽

Mrna Expression ◽

Prognostic Significance ◽

Family Members ◽

Incidence Rates ◽

Human Gastric Cancer ◽

Kaplan Meier ◽

E2f Transcription Factors ◽

Transcription Activators

Gastric cancer (GC) is the second most frequent cause of cancer-related mortality in the world, with Eastern Asia having the highest incidence rates. E2F is a family of transcription factor proteins that has a variety of functions, which include control of cell cycle, cell differentiation, DNA damage response and cell death. E2F transcription factors are divided into two subfamilies: transcription activators (E2F transcription factors 1 (E2F1), 2 (E2F2) and 3a (E2F3a)) and repressors (E2F3b, E2F transcription factors 4 (E2F4), 5 (E2F5), 6 (E2F6), 7 (E2F7) and 8 (E2F8)). Studies have demonstrated that E2F had prognostic significance in a number of cancers. However, the entirety of the prognostic roles of E2F mRNA expression in GC has not yet been apparently determined. In the present study, the prognostic value of individual family members of E2F mRNA expression for overall survival (OS) was evaluated by using online Kaplan–Meier Plotter (KM Plotter) database. Our result demonstrated that high expressions of three family members of E2F (E2F1, E2F3, E2F4) mRNA were significantly associated with unfavourable OS in all GC patients. However, increased expressions of E2F2, E2F5, E2F6 and E2F7 were significantly associated with favourable OS, especially for higher clinical stages in GC patients. These results provided a better insight into the prognostic functions of E2F mRNA genes in GC. Although the results should be further verified in clinical trials, our findings may be a favourable prognostic predictor for the development of newer therapeutic drugs in the treatment of GC.

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