• Title/Summary/Keyword: Gene survival

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Reconstruction and Exploratory Analysis of mTORC1 Signaling Pathway and Its Applications to Various Diseases Using Network-Based Approach

  • Buddham, Richa;Chauhan, Sweety;Narad, Priyanka;Mathur, Puniti
    • Journal of Microbiology and Biotechnology
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    • v.32 no.3
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    • pp.365-377
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    • 2022
  • Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

Effect of Clove Extracts on Tyrosinase Gene Expression (정향(Clove) 추출물이 티로시나아제 유전자의 발현에 미치는 효과)

  • Chin, Jong-Eon;Lee, Jeong-Yong;Kim, Kwan-Chun
    • Journal of environmental and Sanitary engineering
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    • v.22 no.1 s.63
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    • pp.75-83
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    • 2007
  • Clove extract by methanol increased expression of the tyrosinase gene on B16 mouse melanoma cells containing tyrosinase promoter. $10{\mu}g/mL$ and $100{\mu}g/mL$ of the extract showed expression rate of the tyrosinase gene about 138% and 245%, respectively, compared with control. At $500{\mu}g/mL$, expression rate of the extract was impossible to measurement by high cytotoxicity. The solvent fraction of methylene chloride also exhibited highly expression rate as methanol extract. However, the solvent fractions of butyl alcohol and water showed repressive effect on expression of tyrosinase gene at $500{\mu}g/mL$. In MTT assay, cell survival rate of the extract exhibited similar to expression rate of tyrosinase gene. That is, $10{\mu}g/mL$ and $100{\mu}g/mL$ of the extract showed the cell survival rate about 128% and 187%, respectively.

Epidermal Growth Factor Receptor Gene Polymorphisms and Gastric Cancer in Iran

  • Abediankenari, Saeid;Jeivad, Fereshteh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3187-3190
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    • 2013
  • Background: Epidermal growth factor receptor (EGFR) is a transmembrane receptor which contributes to many processes involved in cell survival, proliferation and inhibits apoptosis, that may lead to cancer development. Gastric cancer is one of the most common diseases of digestive system that has low 5-year-survival. The aim of this research was to determine the significance of EGFR tyrosine kinase domain gene polymorphisms in gastric cancer in Iran. Materials and Methods: In the present study, 83 patients with gastric cancer and 40 normal subjects were investigated for EGFR gene polymorphisms in exons 18-21 by PCR-SSCP. Then, DNA sequencing was conducted for different mobility shift bands. Finally the data were statistically analyzed using the chi-2 test and the SPSSver.16 program. Results: Exon 18 of EGFR gene showed three different bands in SSCP pattern and DNA sequencing displayed one mutation. SSCP pattern of Exons 19 and 21 did not show different migration bands. Exon 20 of EGFR gene revealed multiple migrate bands in SSCP pattern. DNA sequencing displayed 2 mutations in this exon: one mutation was caused amino acid change and another mutation was silent. Conclusion: It may be that EGFR tyrosine kinase gene polymorphisms differ between populations and screening could be useful in gastric cancer patients who might benefit from tyrosine kinase inhibitor therapy.

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

  • Wu, San-Yun;Yu, Ming-Xia;Li, Xiao-Gai;Xu, Shu-Fang;Shen, Ji;Sun, Zhen;Zhou, Xin;Chen, Xing-Zhen;Tu, Jian-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3299-3304
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    • 2014
  • Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

Predictive Role of Glutathione-S-transferase Gene Polymorphisms in the Survival of Gastric Cancer Cases

  • Wang, Zhao-Yang;Zhou, Jing;Luo, Li;Huang, Ying-Long;Dong, Pei-De
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1515-1518
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    • 2012
  • Aim: We conducted a prospective study in an Chinese population to detect the association between GSTM, GSTT and GSTP gene polymorphisms and survival of gastric cancer. Methods: A prospective follow-up study with 317 gastric cancer patients was conducted between January 2003 and January 2005. GSTM1, GSTT1 and GSTP1 genotyping was performed using ABI TaqMan Gene Expression assays. Results: Of 317 patients, 5 were lost to follow-up due to migration, while the remaining 302 patients completed the study. The median follow-up time was 34.2 months (range: 2 to 60 months), during which a total of 120 (39.1%) died of gastric cancer. The GSTT1-null genotype showed a significant increased risk of death from gastric cancer, with an HR (95% CI) of 1.59 (1.04-3.58). Moreover, we found individuals carrying null-GSTM1 and null-GSTT1 had a moderate higher risk of death from gastric cancer, with an HR of 1.92 (1.05-3.65). Conclusion: This study reported the carriage of null GSTT1 and null GSTM1 might be linked to the higher death risk from gastric cancer in Chinese population.

Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases

  • Rashed, Reham A;Kadry, Dalia Y;Taweel, Maha EL;Abd El Wahab, Nahed;Abd El Hameed, Thoreya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7875-7882
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    • 2015
  • Background: The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. Materials and Methods: This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. Results: BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p-value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value=<0.001, 0.045, 0.041, <0.008 and 0.025 respectively). Conclusions: Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.

Effect of Sonication and vir Genes on Transient Gene Expression in Agrobacterium-Mediated Transformation (Agrobacterium을 이용한 형질전환에서 sonication과 vir 유전자들의 효과)

  • 이병무
    • Journal of Life Science
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    • v.11 no.4
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    • pp.316-320
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    • 2001
  • Sonication tremendously improves the efficiency of Agrobacterium infection by introducing small and uniform fissures and channels throughout the targeted tissue. Using shoot tips of cotton as explants, the effect of sonication treatment and virulence genes in Agrobacterium tumefaciens on transformation efficiency was investigated. The pat gene which encodes resistance to the herbicide, glufosinate, was used as a selectable marker. Transformation efficiency was evaluated on th basis of survival rates of cocultivated shoot tips on selection medium containing 2.5 mg/l gulfosinate-ammonium(ppt) adn 25. mg/l Clavamax. Sonication from 5 to 15 second has a positive effect on shoop tip survival. However, whil virE as well as virG or vir GN54D showed an enhancement in transformation efficiency, virE,. virG resulted in the most significant enhancement. Overall, the combination of additional virG/virE gene and sonication treatment resulted in the most significant increase in transformation efficiency.

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XRCC1 Gene Polymorphism, Clinicopathological Characteristics and Stomach Cancer Survival in Thailand

  • Putthanachote, Nuntiput;Promthet, Supannee;Suwanrungruan, Krittika;Chopjitt, Peechanika;Wiangnon, Surapon;Chen, Li-Sheng;Yen, Ming-Fang;Chen, Tony Hsiu-Hsi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6111-6116
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    • 2015
  • Background: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. Materials and Methods: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. Results: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. Conclusions: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

고려인삼으로부터 Squalene Synthase 유전자의 Cloning 및 형질전환체 특성

  • Sim, Ju-Seon;Son, Hwa;Yang, Deok-Chun
    • Proceedings of the Ginseng society Conference
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    • 2004.12a
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    • pp.50-52
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    • 2004
  • Introduce of gene connected with disease and transformation system of ginseng, Squalene systhase(PSS) gene cloned from and disease resistant gene were carried out for expression and transformation of plant using Agrobacterium. PSS of 35S-35S-AMV-PSS-Tnos, has been constructed which were mobilized into Agrobacterium tumefaciens strain MP 90 disarmed Ti-plasmid. PSS gene were introduced into the binary vector pRD 400. The transgenic ginseg plants were propagated using repetitive secondary embryogenesis and introduced NPTII and PSS genes of the transgenic ginseng were successfully indentified by the PCR and survival test on the medium.

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Overexpression of Twist and Matrix Metalloproteinase-9 with Metastasis and Prognosis in Gastric Cancer

  • Gao, Xing-Hui;Yang, Xue-Qin;Wang, Bi-Cheng;Liu, Shao-Ping;Wang, Fu-Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5055-5060
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    • 2013
  • Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.