CT Gene Research Articles

Correlation between CT based radiomics features and gene expression data in non-small cell lung cancer.

Radiogenomics investigates radiographic imaging phenotypes associated with gene expression patterns. This study aims to explore relationships between CT imaging radiomics features and gene expression data in non-small cell lung cancer (NSCLC). Eighty-nine NSCLC patients are included in the study. Radiomics features are extracted and selected to quantify the phenotype of tumors on CT-scans. Co-expressed genes are also clustered and the first principal component of the cluster is represented, which is defined as a metagene. Then, statistical analysis was performed to assess association of CT radiomics features with metagenes. In addition, predictive models are built and metagene enrichment are conducted to further evaluate performance of NSCLC radiogenomics statistically and biologically. There are 187 significant pairwise correlations between a CT radiomics feature and a metagene of NSCLC, where eighteen metagenes are annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Metagenes are predicted in terms of radiomics features with an accuracy of 41.89% -89.93%. This study reveals the associations between CT imaging radiomics features and NSCLC co-expressed gene sets. The findings suggest that CT radiomics features can reflect important biological information of NSCLC patients, which may have a significant clinical impact as CT is routinely used in clinical practice, assisting in improving medical decision-support at low cost.

Comparative analysis of biochemical parameters and gene expressions of novel markers in type II Diabetes mellitus

Background: Diabetic nephropathy (DN) is the most common cause of end stage renal disease (ESRD). Early detection of the disease and treatment of this chronic complication which would reduce the medical and economic burden. Early detection of kidney injury by evaluating gene expressions of Il-6, Il-10, LDLr, and CD36 in T2DM with pre-ESRD microalbuminuria minimizes the risk of DN. Methods: Present research work conducted at the Department of Biochemistry, School of Medicine, Navi Mumbai. This study includes 241 subjects (118 male, 123 women, and age ranges 30-70 years) were included after screening for T2DM by measurement of blood glucose in fasting, post-prandial, glycosylated haemoglobin. Microalbumin in urine and e-GFR is measured to eliminate patients of ESRD. Subjects were recruited after written consent and enrolled as per inclusion/exclusion criteria. Categorization of subjects in three study groups; group I (30-45 years), group II (46-70 years) were done on the basis of T2DM duration 3-6 years, glycosylated haemoglobin level (HbA1c) ≥ 7.0% with fasting blood glucose ≥126 mg/dl) and microalbuminuria (30-300 mg/dl) in study group, equal numbers of healthy volunteers enrolled in control group. Blood samples were processed for other renal parameters and RT-PCR to check expressions of novel genes Results: In study groups all renal, lipids parameters are within normal range except albumin/creatinine ratio (p <0.012), e-GFR (p <0.00) and cholesterol (p <.00). Descriptive analysis showed high significance (p <.00) of delta CT gene expressions, parameters in pre-ESRD microalbuminuria subjects. Conclusion: Screening biochemical renal parameters are not enough to prevent DN even in microalbuminuria. Early detection of gene expressions of novel biomarkers predicts risk of kidney injury. Early intervention may prevent morbidity and mortality of kidney due to diabetic nephropathy.

The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China

The methylenetetrahydrofolate reductase (MTHFR) genotypes 677CT and 677TT are associated with elevated serum homocysteine (Hcy) levels by means of lowering the activity of MTHFR, and the increase in serum Hcy may be linked to increased susceptibility to non-alcoholic fatty liver disease (NAFLD). However, there are contradictory reports of the relationship among the MTHFR 677CT gene polymorphism, Hcy, and NAFLD. Therefore, the aim of this study was to identify potential associations and interactions of either Hcy levels or the MTHFR 677CT gene polymorphism with the susceptibility to NAFLD in a Chinese population. The association between the MTHFR 677 CT gene polymorphism and Hcy levels was determined in 243 subjects with NAFLD and 388 healthy subjects without NAFLD using polymerase chain reaction-restriction fragment length polymorphism analysis and high-performance liquid chromatography. In subjects with NAFLD, there was no statistical difference in the genotypic and allelic frequencies of the MTHFR 677 CT gene polymorphism, while serum Hcy levels were significantly higher in subjects with NAFLD. Furthermore, these results strongly suggest that the MTHFR 677CT gene polymorphism and NAFLD have a potential synergistic effect on Hcy elevation, although the MTHFR 677CT gene polymorphism was not correlated with NAFLD in a Chinese population.

METHODICAL APPROACHES TO THE APPLICATION OF GENES VARIATIONS AS INDICES OF SUSCEPTIBILITY IN THE HEALTH RISK ASSESSMENT

The biological characteristics of the organism, including the genetic status, can be taken as the indices of the individual susceptibility. These susceptibility indices can be applied in the health risk assessment if there is shown the probability of the development of disorders induced by the exposure to environmental factors and if their cause-and-effect relationship with the exposure of these factors is proved. To distinguish the indices values of the individual susceptibility to the health risk formation in conditions of the exposure to the environmental and occupational factors it is proposed to perform consecutive identification of the contingents, risk factors and their probable effects; evaluation of the exposure of risk factors, including the use of exposure markers; genetic testing of the risk contingents; the establishment of a cause-effect relation of the likely effects (responses) with the exposure of these factors; modeling of the dependence of the probable effects (responses) on the exposure of the studied factors for subpopulations with different susceptibility indices; the characteristics of the health risk with an assessment of the additional probability (frequency) of the studied effects (responses) in subpopulation with susceptibility indices. When testing the proposed methodological approaches it was established that it is possible to use the CT gene variation FAS as an index of the individual susceptibility to the development of diseases of the upper respiratory tract with inhalation exposure to vanadium, AG gene variation HTR2A index of the individual susceptibility to the forming of feeding redundancy in peroral exposure to chloroform, CT heterozygote gene variation MTHFR index value of the individual susceptibility to the forming of the pathology of the circulatory system (hypertension) under exposure to the noise. The proposed methodological approaches for the assessment of the individual health risk associated with the exposure to the environmental factors allow more exactly defining the results of the health risk assessment for the individuals with genotype variations that do the conditioning of the excessive individual susceptibility.

АЛЕЛЬНИЙ ПОЛІМОРФІЗМ С-260Т ГЕНА CD14 У ДІТЕЙ ІЗ ПОВТОРНИМИ ЕПІЗОДАМИ ГОСТРОГО ОБСТРУКТИВНОГО БРОНХІТУ

У структурі захворюваності дітей віком 0–14 років хвороби органів дихання займають перше місце та складають 62,0–65, 0 %. Пильну увагу дослідники та практичні лікарі до вказаної патології прикуто як її медичною та соціальною значимістю, так і відсутністю чітких критеріїв діагностики, необхідністю диференційованого підходу до лікування та реабілітації дітей. Особливий інтерес представляють повторні обструкції нижніх дихальних шляхів у дітей унаслідок неоднорідності причин, що їх спричиняють, подібності клінічної симптоматики та обмеженої інформативності загальноприйнятих методів дослідження.Мета дослідження – пошук молекулярно-генетичних маркерів підвищеної схильності дітей до повторних епізодів гострого обструктивного бронхіту.Матеріали і методи. Обстежено 25 дітей у віці від 2 до 8 років із повторними епізодами гострого обструктивного бронхіту (ГОБ). Для порівняння отриманих даних дітей із повторними епізодами ГОБ було відібрано групу із 25 дітей у віці від 2 до 8 років, які хворіли на гострий бронхіт (ГБ) не частіше 1–2 разів на рік, і склали групу порівняння. Результати молекулярно-генетичного дослідження порівнювали з даними 25 осіб, які взяли методом випадкової вибірки, які увійшли до загальнопопуляційної групи контролю.Результати досліджень та їх обговорення. Не зареєстровано достовірно вищої частоти генотипів СС, СТ та ТТ поліморфного локусу С-260Т гена CD14 у дітей із повторними епізодами гострого обструктивного бронхіту.Висновки. Проведене дослідження показало, що генотип СС поліморфного локусу С-260Т гена CD14 зустрічається частіше в дітей із гострим бронхітом, порівняно з пацієнтами із повторними епізодами ГОБ (44,0 проти 28,0 %), хоча достовірної різниці не зафіксовано, що, на думку авторів, вимагає подальших досліджень і збільшення кількості спостережень.

The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan? methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ? 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3?5 *3*3 allele. All of these patients had CYP3?4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

Cancer/Testis genes in relation to sperm biology and function.

Cancer testis antigens (CTAs), a large family of tumor-associated and immunogenic antigens expressed in human tumors of various histological origins, are highly restricted to the testis and trophoblast. CTAs have been identified as potent targets for tumor-specific immunotherapeutic advances and have immensely lead to the development of different clinical trials of CTA-based vaccine therapy because of their resilient in vivo immunogenicity and tumor-restricted expression pattern. Bladder cancer, non-small cell lung carcinoma, and melanoma are grouped as high CT gene expressors. Prostate and breast cancer as moderate, and colon and renal cancers are considered as low CT gene expressors. Large percentages of these identified CT genes are expressed during spermatogenesis but their function is still vaguely unknown. Researchers have taken a keen interest in CT genes as pertaining to their role in tumor growth and spermatogenesis. Testis has many similarities with cancerous tissues like cell division, immigration, and immortalization. The aim is to give a concise in-depth review on the role of some specific CT genes in spermatogenesis.

Relationship Between Genetic Polymorphism and Tacrolimus Concentration-Dose Ratio in Renal Transplant Patients

Tacrolimus concentration-dose ratio, as a potential therapeutic drug monitoring strategy, has been suggested to be used for the renal transplant patients. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio and the polymorphisms of genes encoding the most important enzymes, such as CYP3A4/5, as well as the transporter P-glycoprotein, for its metabolism and elimination. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real-Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Patients who were treated with less than 2 mg of tacrolimus/day (0.024±0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/ml/mg/kg. In this group, 84.62% patients had CYP3A5 *3*3 allele (CYP3A5 nonexpressers). All of these patients had CYP3A4 *1*1/*1*1B allele (CYP3A4 expressers). Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant (diminished activity of ABCB1 transporter), while 69.23% of our patients had CC and CT gene variants. Tacrolimus concentration-dose ratio greater than 150 ng/ml/mg/kg is cut-off value in renal transplant patients which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

FT19. Combination of Preoperative CT and Carotid Plaque Gene Expression Profiling Demonstrates an Association Between Calcification and Plaque-Stabilizing Processes

FT19. Combination of Preoperative CT and Carotid Plaque Gene Expression Profiling Demonstrates an Association Between Calcification and Plaque-Stabilizing Processes

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

BackgroundCancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.MethodssiRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.ResultsDepletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.ConclusionsTEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

SOX6 expression level in brain tumors

Abstract Introduction: Due to the importance of SOX6 expression in brain tumors as a promising diagnostic and therapeutic target, we tried to systematically review existed information regarding the expression pattern of this CT gene in human normal and cancerous brain tissues. Method: PubMed was searched with the following search strategy: (SOX 6 OR SOX6 OR SOX-6) AND tumor, on Oct-2015. All types of articles, which studied the quantitative aspect or the intensity of the expression of the SOX6 in patients with different types of brain tumors, were included in this systematic review. There was not restriction regarding the date of publication or the language of the obtained articles. Results: Totally, 125 articles were obtained following the initial search in PubMed. Majority of the obtained articles were irrelevant with the aim of the study due to investigating other types of tumors except brain tumors. Eventually 5 articles were completely eligible to be involved. Discussion: Based on presented articles results, glioma tissue cells shows genes expression pattern compatible and well matched with developing CNS cells. Regarding the relation of SOX6 in oncogenesis, it seems that SOX6 does not stimulate proliferation however affect the early stage of oncogenesis in gliomas by inducing transformation activity. Conclusion: High rate of SOX6 expression made it a considerable choice as a therapeutic and diagnostic marker; however more accurate information on the protein expression pattern is essential

Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs.

The association between the common variants of thyroid hormone receptor interactor 4 gene and Alzheimer disease

Objective To explore the association between the common variations of thyroid hormone receptor interactor 4(TRIP4) gene rs4776494 and Alzheimer disease(AD) in Chinese people. Method A case-control study was performed, consisting of 77 patients with AD(AD group) and 80 controls(control group) who were matched at age and gender with the AD patients. PCR and sequencing were used to determine the distribution of allele and genotype frequency of TRIP4 rs4776494.Every case was subjected to mini-mental state examinations(MMSE), clinical dementia rating(CDR) and behavioral and psychological symptoms of dementia(BPSD). Results The TT, CT and CC gene frequencies were 57/77(74.02%), 18/77(23.38%) and 2/77(2.6%) in AD group, and 38/80(47.5%), 39/80(48.75%) and 3/80(3.75%) in control group, respectively. T allele in cases group was significantly higher than that in control group(P<0.01). Cases with T allele were more susceptible to BPSD than those without T allele(P<0.05). Conclusion T Allele of TRIP4 rs4776494 might be a genetic risk factor of AD in Chinese population.To some degree, TRIP4 gene may be associated with mental symptoms in AD patients. Key words: Alzheimer disease; TRIP4; Single nucleotide polymorphism

MARKERS OF CONNECTIVE TISSUE REMODELING IN GENITAL PROLAPSE

Purpose: to expand the conception of molecular and biochemical changes in genital prolapse (GP) based on the study of morphological and immunohistochemical features in connective tissue structures of the ligamentous apparatus of the pelvic floor and their dependence on genetic polymorphisms MMP / TIMP. Materials and Methods: the study involved 178 women aged 35 to 65, 134 of them with GP relapses (after hysterectomy by vaginal access because of a total and partial uterus and vaginal walls prolapse). Patients were randomized into the following groups: I – with manifestations of undifferentiated connective tissue dysplasia (CTD) (11.7 points on average) (n = 86); II – with no CTD signs (n = 48). Control group lll consisted of healthy women without any GP signs (among 15 patients abdominal hysterectomy was performed in connection with uterus hyperplastic processes) (n = 44). Used: morphological method of studies, immunohistochemical (to assess tissue biopsies of sacrum-uterine and round uterine ligaments), the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs), genotyping by polymerase chain reaction of MMP / TIMP polymorphisms. Results: the morphological study of women’s ligamentous apparatus in cases with GP revealed significant fibrosis, coarser collagen septa among bundles of smooth muscle fibers and degenerative changes in individual smooth muscle cells. The group with GP and CTD features showed diffuse atrophy, hyaline or mucinous degeneration of smooth muscle tissue and evident edema of extracellular matrix in 65% of samples. Pathobiochemical disorders in cases of pelvic descencia were determined by an imbalance in collagen type I and III content, with the predominance of the latter, less durable; a decrease in elastin levels and its considerable fragmentation. The greatest expression of tissue degradation was observed among women with GP and CTD manifestations on account of increased MMP-1 and -2 levels; TIMP-1 content was lowest in the group. Associations with GP development have been established among women with CTD signs for genetic polymorphisms: rs3918242 СT gene MMP9 (0,54) (p = 0,007; OR = 3,2; 95% CI 1,3-7,6), rs17576 AG gene MMP9 (0.62 vs. 0,32, p = 0,01; OR = 2,9; 95% CI 1,2-7,0); rs3025058 5A6A gene MMP3 (0.52 vs. 0.45, p = 0.009; OR = 3.7; 95% CI 1,3-10,1); rs2285053 (rs2285052) CT gene MMP2 (0.44 vs. 0.27, p = 0,007; OR = 3,2; 95% CI 1,3-7,5). Statistical significance for the groups was preserved after the correction for multiple comparisons. Summary: the data obtained reveal pathogenetic aspects of genital prolapse – the prevalence of extracellular matrix degradation in a dysplastic morphogenesis. Genetic predictors of pelvic floor remodeling including the formation of its insolvency were established, allowing to extend the range of diagnostic possibilities of the disease progression at early stages or detection the risk of recurrence after surgical treatment. Personification of high-risk groups conducting provides for the exclusion or modification of all the factors predisposing to the development of the disease and performing timely treatment and preventive measures.

Features of coronary heart disease development in emergency workers of the Chornobyl accident depending on the action of radiation and non-radiation risk factors and genotypes of single nucleotide polymorphism rs966221 of phosphodiesterase 4D gene

This study devoted to specific features of coronary heart disease (CHD) development in emergency work ers (EW) of the accident at the Chernobyl nuclear power plant (ChNPP) based on analysis the interaction between radiation and non radiation risk factors and single nucleotide polymorphism (SNP) rs966221 of phosphodiesterase (PDE) 4D gene. It was examined 397 men with CHD, including 274 EW of 1986-1987 and 123 non irradiated persons (con trol group) who were 66±10 and 69±11 years old relatively. The program studies included clinical examination, elec trocardiography (ECG), ECG daily monitoring, ECG stress testing, echo doppler cardiography, analysis of serum lipid spectrum, polymerase chain reaction with restriction of reaction products, retrospective analysis of case histories. Diagnosis of CHD or its approval was carried out in accordance with the standards of diagnosis, accepted in Ukraine. All EW before their taking part in cleaning ChNPP territory did not suffered from CHD. According to the analysis of contingency tables, carriers of the TT genotype of rs966221 increased the risk of myocardial infarction (MI) in 2.538 times compared with carriers of genotypes CC and CT. The use of Kaplan Meier method showed that a half of EW with the TT genotype developed MI before 64 years old, while with the other geno types up to 78.7 years old. In the control group statistically significant increase of cumulative proportion of patients with MI, carriers of the TT genotype, began from 60 years old. Compared to the non irradiated patients EW fell ill with CHD on 9.4 years earlier. Using proportional hazards analysis (Cox regression), it was found that EW had 3.9 times higher risk of CHD than in non irradiated individuals. Smoking and overweight brought three times less but significant risk - 1.37 and 1.33 respectively. The TT genotype unlike genotypes CC and CT gene PDE4D increased risk of MI in 1.757 times more both in EW and control group. The risk of CHD development was determined by radiation factor, such as the involvement in the emer gency works of the accident consequences, as well as non radiation factors, namely smoking and overweight. Only one factor, the TT genotype of rs966221 PDE4D gene, determined the risk of MI occurrence in EW and non irradiated controls. In the post emergency period, CHD developed 6 years earlier in EW with the TT genotype than in patients with genotypes CC and CT.

Estimation of Salt Tolerance Degree in some Selected Wheat Genotypes by Using Detection of Salt Tolerant Gene (TaSTK) and its Expression Under Salinity Conditions

Molecular studies were carried out to detect salt tolerance gene (TaSTK) and estimate their expression in two selected cultivars (Dijilla and Furat) and one genotype (N3) of wheat under salinity condition (0, 15, 25 ds/m) as compared with salt sensitive cultivar (Tamooze-2). These cultivars and genotype were selected through plant breeding programs. The cDNA and gene amplification method used for this detection. Real-time PCR sybergreen method used to estimate the CT values and gene expression. The gene band length is 150 bp which appeared only in the selected materials (salt tolerance), while this gene absent in the salt sensitive culture (Tamooze-2). Amount and expression of TaSTK gene to be enhanced under salt conditions, and the degree of salt related enhancement was greatly only in salt-tolerant materials. Excess expression and amount of the TaSTK gene were at high salinity levels. At all salinity levels also the results showed that the amount and expression of this gene were proximately similar in all selected materials by contrast, there were no amount and expression of this gene in sensitive culture (local cultivar).

'Sex' in the cancer cell.

'Sex' in the cancer cell.

Association of polymorphisms at HORMAD2 and prognosis in advanced non-small-cell lung cancer patients

BackgroundCancer–testis (CT) genes are predominantly expressed in the testis and are ectopically activated in a wide range of cancers. The expression of CT antigens has been shown to significantly affect the survival of patients with non-small-cell lung cancer (NSCLC). Recently, a genome-wide association study (GWAS) and expression analysis have identified a novel CT gene (HORMAD2) associated with lung cancer risk in Han Chinese people. Thus, the aim of this study is to evaluate the potential prognostic value of HORMAD2 polymorphisms in Han Chinese patients with advanced NSCLC and undergoing first-line platinum-based chemotherapy. Materials and methodsWe selected eight single-nucleotide polymorphisms (SNPs) of HORMAD2 with the potential function of affecting the binding of transcription factors, and we genotyped these SNPs in 303 patients with advanced NSCLC using the MassARRAY platform. All patients were treated with first-line platinum-based chemotherapy but without surgery. Log-rank test and Cox proportional hazard models were used for the survival analyses. ResultsFour SNPs at HORMAD2 (rs9620953, rs8135823, rs5753025 and rs9625921) were significantly associated with the survival of advanced NSCLC patients. Among these, patients with the rs9620953 T allele had a significantly reduced risk of death compared to those with the C allele (additive model: HR, 0.53, 95%CI, 0.32–0.89, P=0.016; dominant model: HR, 0.50, 95%CI, 0.29–0.84, P=0.010). Similarly, the G allele at rs8135823 could decrease the death risk of NSCLC patients compared to the T allele (additive model: HR, 0.63, 95%CI, 0.41–0.95, P=0.028; dominant model: HR, 0.60, 95%CI, 0.39–0.93, P=0.022). Furthermore, both the rs5753025 C allele and the rs9625921 G allele also decreased the death risk in NSCLC in different genetic models (additive model for rs5753025: HR, 0.80, 95%CI, 0.65–0.98, P=0.032; heterozygote model for rs9625921: HR, 0.71, 95%CI, 0.51–0.99, P=0.040). In the joint effect analyses, we found that patients with one, two, and three to eight favorable alleles had a better survival compared with patients carrying no alleles. ConclusionsThese findings indicate that polymorphisms at the CT gene HORMAD2 might be involved in the prognosis of advanced NSCLC in Han Chinese. Further larger and functional studies are needed to confirm the results.

Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers.

Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using The Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8, and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically, whereas others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CT expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.

Association of -24CT, 1249GA, and 3972CT ABCC2 Gene Polymorphisms with Methotrexate Serum Levels and Toxic Side Effects in Children with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia patients after being treated with methotrexate, have differences in methotrexate serum levels and toxic side effects. One of the main determinants of these toxic side effects is the host pharmacogenetics. The aim of this study was to evaluate the association of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with serum levels, and toxic side effects of methotrexate in childhood acute lymphoblastic leukemia. Applying polymerase chain reaction and restriction fragment length polymorphism techniques, the prevalence of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms was evaluated in 65 acute lymphoblastic leukemia patients. The relationship between polymorphisms and methotrexate serum levels and toxicities was studied. A reverse significant relationship was detected between 3972T allele carriers and hepatotoxicity (P = 0.01, OR = 0.25, 95% CI = 0.09–0.72). Also, 1249A allele carriers had increased rate of gastrointestinal toxicity (P = 0.05, OR = 3.47, 95% CI = 1.04–11.57). No significant relationship was detected between -24CT polymorphism and methotrexate toxic side effects. There was no significant relationship between these three polymorphisms and methotrexate serum levels. Genotyping for 3972CT and 1249GA ABCC2 gene variants maybe useful in acute lymphoblastic leukemia to optimize methotrexate therapy and reducing the associated toxicity.