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

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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Expression of LOX Suggests Poor Prognosis in Gastric Cancer

Frontiers in Medicine ◽

10.3389/fmed.2021.718986 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jinfeng Zhu ◽

Chen Luo ◽

Jiefeng Zhao ◽

Xiaojian Zhu ◽

Kang Lin ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Logistic Regression ◽

Regression Analysis ◽

Poor Prognosis ◽

Cox Regression ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Expression Level ◽

Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

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Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry

Journal of Translational Medicine ◽

10.1186/s12967-021-03203-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Hee Young Na ◽

Yujun Park ◽

Soo Kyung Nam ◽

Jiwon Koh ◽

Yoonjin Kwak ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

B Cells ◽

Nk Cells ◽

Natural Killer ◽

Immune Cells ◽

Nk Cell ◽

Critical Role ◽

Killer Cell ◽

Prognostic Significance

Abstract Background Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC). Methods We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells. Results Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival. Conclusions Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.

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High expression of GNB4 predicts poor prognosis in patients with Helicobacter pylori-positive advanced gastric cancer

Translational Cancer Research ◽

10.21037/tcr-19-2914 ◽

2020 ◽

Vol 9 (7) ◽

pp. 4224-4238

Author(s):

Jianpeng Gao ◽

Teng Yu ◽

Yi Xuan ◽

Zhenglun Zhu

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Advanced Gastric Cancer ◽

Poor Prognosis ◽

High Expression

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Prognostic value of biglycan in gastric cancer

10.21203/rs.3.rs-103093/v1 ◽

2020 ◽

Author(s):

Sizhe Hu ◽

Peipei Li ◽

Chenying Wang ◽

Xiyong Liu

Keyword(s):

Gastric Cancer ◽

Transcription Factors ◽

Poor Prognosis ◽

Prognostic Significance ◽

Bioinformatic Analysis ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Mrna Levels ◽

Gene Signatures ◽

Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

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High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.15104 ◽

2020 ◽

Vol 24 (8) ◽

pp. 4452-4465 ◽

Cited By ~ 9

Author(s):

Huafu Li ◽

Qiao Su ◽

Bo Li ◽

Linxiang Lan ◽

Chunming Wang ◽

...

Keyword(s):

Gastric Cancer ◽

T Lymphocyte ◽

Poor Prognosis ◽

High Expression ◽

Lymphocyte Infiltration

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[Corrigendum] High expression of RELM-α correlates with poor prognosis and promotes angiogenesis in gastric cancer

Oncology Reports ◽

10.3892/or.2018.6933 ◽

2018 ◽

Author(s):

Ping Chen ◽

Deshou Zhao ◽

Weiyi Wang ◽

Yongping Zhang ◽

Yaozong Yuan ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

High Expression

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High expression of nucleobindin 2 is associated with poor prognosis in gastric cancer

Tumor Biology ◽

10.1177/1010428317703817 ◽

2017 ◽

Vol 39 (7) ◽

pp. 101042831770381 ◽

Cited By ~ 1

Author(s):

Bolag Altan ◽

Kyoichi Kaira ◽

Shuichi Okada ◽

Tsugumichi Saito ◽

Eijiro Yamada ◽

...

Keyword(s):

Gastric Cancer ◽

Poor Prognosis ◽

High Expression

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Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members

Blood ◽

10.1182/blood.v99.1.61 ◽

2002 ◽

Vol 99 (1) ◽

pp. 61-66 ◽

Cited By ~ 168

Author(s):

Kazuhiro Kogawa ◽

Susan M. Lee ◽

Joyce Villanueva ◽

Daniel Marmer ◽

Janos Sumegi ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Cd8 T Cells ◽

Hemophagocytic Lymphohistiocytosis ◽

Family Members ◽

The Other ◽

Cytotoxic Lymphocytes ◽

Color Flow ◽

Cytotoxic Cells ◽

Perforin Expression

Mutations in the perforin gene have been described in some patients with hemophagocytic lymphohistiocytosis (HLH), but the role of perforin defects in the pathogenesis of HLH remains unclear. Four-color flow cytometric analysis was used to establish normal patterns of perforin expression for control subjects of all ages, and patterns of perforin staining in cytotoxic lymphocytes (natural killer [NK] cells, CD8+ T cells, CD56+ T cells) from patients with HLH and their family members were studied. Eleven unrelated HLH patients and 19 family members were analyzed prospectively. Four of the 7 patients with primary HLH showed lack of intracellular perforin in all cytotoxic cell types. All 4 patients showed mutations in the perforin gene. Their parents, obligate carriers of perforin mutations, had abnormal perforin-staining patterns. Analysis of cytotoxic cells from the other 3 patients with primary HLH and remaining family members had normal percentages of perforin-positive cytotoxic cells. On the other hand, the 4 patients with Epstein-Barr virus–associated HLH typically had depressed numbers of NK cells but markedly increased proportions of CD8+ T cells with perforin expression. Four-color flow cytometry provides diagnostic information that, in conjunction with evidence of reduced NK function, may speed the identification of life-threatening HLH in some families and direct further genetic studies of the syndrome.

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