CT Gene Research Articles

Study on the relationship between KCNQ1 gene-environment interaction and abnormal glucose metabolism in the elderly in a county of Hechi City, Guangxi.

This study aimed to understand the potassium voltage-gated channel KQT-like subfamily, member 1 gene polymorphism in a rural elderly population in a county in Guangxi and to explore the possible relationship between its gene polymorphism and blood sugar. The 6 SNP loci of blood DNA samples from 4355 individuals were typed using the imLDRTM Multiple SNP Typing Kit from Shanghai Tianhao Biotechnology Co. The data combining epidemiological information (baseline questionnaire and physical examination results) and genotyping results were statistically analyzed using GMDR0.9 software and SPSS22.0 software. A total of 4355 elderly people aged 60 years and above were surveyed in this survey, and the total abnormal rate of glucose metabolism was 16·11 % (699/4355). Among them, male:female ratio was 1:1·48; the age group of 60-69 years old accounted for the highest proportion, with 2337 people, accounting for 53·66 % (2337/4355). The results of multivariate analysis showed that usually not doing farm work (OR 1·26; 95 % CI 1·06, 1·50), TAG ≥ 1·70 mmol/l (OR 1·19; 95 % CI 1·11, 1·27), hyperuricaemia (OR 1·034; 95 % CI 1·01, 1·66) and BMI ≥ 24 kg/m2 (OR 1·06; 95 % CI 1·03, 1·09) may be risk factors for abnormal glucose metabolism. Among all participants, rs151290 locus AA genotype, A allele carriers (AA+AC) were 0.70 times more likely (0.54 to 0.91) and 0.82 times more likely (0.70 to 0.97) to develop abnormal glucose metabolism than CC genotype carriers, respectively. Carriers of the T allele at the rs2237892 locus (CT+TT) were 0.85 times more likely to have abnormal glucose metabolism than carriers of the CC genotype (0.72 to 0.99); rs2237897 locus CT gene. The possibility of abnormal glucose metabolism in the carriers of CC genotype, TT genotype and T allele (CT + TT) is 0·79 times (0·67-0·94), 0·74 times (0·55-0·99) and 0·78 times (0·66, 0·92). The results of multifactor dimensionality reduction showed that the optimal interaction model was a three-factor model consisting of farm work, TAG and rs2237897. The best model dendrogram found that the interaction between TAG and rs2237897 had the strongest effect on fasting blood glucose in the elderly in rural areas, and they were mutually antagonistic. Environment-gene interaction is an important factor affecting abnormal glucose metabolism in the elderly of a county in Hechi City, Guangxi.

Detection and quantification of splicing variants of Hd3a gene in oil palm

Alternative splicing is a complex process that contributes to the generation of diverse mRNA and protein isoforms, including in oil palm (Elaeis guineensis). Despite their importance, many functions of alternative splicing genes remain poorly characterized. This study aims to investigate splicing variants of gene encoding Heading date 3a in E. guineensis (EgHd3a) using the GenBank database and ClustalW algorithm. To ensure the data accuracy and reliability of design isoform‐ specific primers, special emphasis is given to primer design techniques and validation using polymerase chain reaction (PCR) and quantitative real‐time (qRT)‐PCR analysis. The designed primers demonstrated high specificity and discrimination between mRNA specimens. Nucleotide variations at the 3’‐end influenced the specificity of primers with the addition of GC composition. Furthermore, qRT‐PCR analysis revealed a strong correlation between Ct values and gene concentration for the isoforms which indicates a reliable amplification of EgHd3a. Although two isoforms, Hd3a‐X2 and Hd3a‐X3, showed slightly higher than acceptable PCR efficiency values, caution is advised to prevent non‐specific amplification. Despite the challenge posed by the limitation of primer positioning due to alternative splicing, the chosen primer proved optimal for analysis. This study highlights the importance of considering alternative splicing in gene quantification experiments and provides insights into the critical steps, methods, and quality control measures necessary for accurately detecting alternative splicing events, contributing to understanding this complex biological process.

Overcoming data scarcity in radiomics/radiogenomics using synthetic radiomic features

PurposeTo evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models. MethodsThis study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on “real-world” radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with “real-world” radiomic training data to evaluate their impact on the predictive model's performance. ResultsA prediction model was generated using only “real-world” radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to “real-world” data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so. ConclusionSynthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity.

Development and validation of four TaqMan real-time PCR diagnostics for the identification and quantification of Pratylenchus crenatus, Pratylenchus neglectus, Pratylenchus penetrans and Pratylenchus thornei

Summary Pratylenchus crenatus, P. neglectus, P. penetrans and P. thornei are globally the most commonly occurring species of root-lesion nematodes (RLN). Correct identification and quantification of these nematodes is important for strategic management interventions such as rotation choice and nematicide use. A real-time quantitative PCR can provide a fast and reliable alternative to morphological identification, which requires significant taxonomic experience. A TaqMan hydrolysis probe method based on the 28S rDNA D2-D3 expansion region was developed and validated for the identification and quantification of these four root-lesion nematode species. Standard curves for each target RLN species were generated by plotting known gene copy number, obtained by a ten-fold serial dilution of purified plasmids, with corresponding Ct values. Each standard curve had a strong linear correlation () between Ct value and gene copy number. There was consistent amplification of samples with target species from different geographic locations within the UK, whereas a lack of amplification was noted for selected non-target species: P. coffeae, P. pseudocoffeae, P. vulnus, P. fallax, Globodera rostochiensis, Meloidogyne hapla, Trichodorus primitivus and Bitylenchus hispaniensis. Specificity and sensitivity of the methods were confirmed by three experiments that explored different life stages, increasing the number of target species, and had mixed Pratylenchus samples. Finally, estimates obtained by qPCR methods were compared with counting carried out by microscopy showing a good correlation (). The TaqMan real-time PCR developed in this study provides a specific, fast and accurate quantification of P. crenatus, P. neglectus, P. penetrans and P. thornei.

Enhanced metabolic resistance mechanism endows resistance to metamifop in Echinochloa crus-galli (L.) P. Beauv.

Barnyardgrass (Echinochloa crus-galli (L.) P. Beauv.), one of the worst weeds in paddy fields in China, has been frequently reported evolving resistance to acetyl-CoA carboxylase (ACCase) inhibiting herbicides. However, in the previous research, more attention was paid to target-site resistance (TSR) mechanisms, the non-target-site resistance (NTSR) mechanisms have not been well-established. In this study, the potential mechanism of resistance in a metamifop-resistant E. crus-galli collected from Kunshan city, Jiangsu Province, China was investigated. Dose-response assays showed that the phenotypic resistant population (JS-R) has evolved 4.3-fold resistance to metamifop compared with the phenotypic susceptible population (YN-S). The ACCase CT gene sequencing and relative ACCase gene expression levels studies showed that no mutations were detected in the ACCase CT gene in both YN-S and JS-R, and there was no significant difference in the relative ACCase gene expression between YN-S and JS-R. After the pre-processing of glutathione-S-transferase (GSTs) inhibitor NBD-Cl, the resistance level of JS-R to metamifop was reversed 18.73%. Furthermore, the GSTs activity of JS-R plants was significantly enhanced compared to that of YN-S plants. UPLC-MS/MS revealed that JS-R plants had faster metabolic rates to metamifop than YN-S plants. Meanwhile, the JS-R popultion exhibited resistant to cyhalofop-butyl and penoxsulam. In summary, this study presented a novel discovery regarding the global emergence of metabolic resistance to metamifop in E. crus-galli. The low-level resistance observed in the JS-R population was not found to be related to TSR but rather appeared to be primarily associated with the overexpression of genes in the GSTs metabolic enzyme superfamily.

The multi-omics signature to predict sensitive to anti-epidermal growth factor receptor therapy in RAS wild-type colorectal cancer liver metastases.

e15578 Background: There are nearly half patients with Ras wild-type metastatic colorectal cancer (mCRC) do not response to Anti-EGFR therapy. Identification of patients who are sensitive to anti-EGFR therapy may increase the response rate and reduce the adverse effect. In this study, we aimed to develop and validate a multi-omics deep learning model to predict cetuximab efficacy in RAS wild type mCRC patients. Methods: In this study, we retrospectively analyzed 213 Ras wild type mCRC patients. The training and testing cohorts comprised patients in Arm A (FOLFOX + cetuximab) of the CHINESE study (NCT01564810) and patients in the CHINESE follow-up study (PMID: 30305811). The external and negative validation cohorts were derived from an independent cohort and Arm B (FOLFOX) of the CHINESE study, respectively. Based on the deep learning framework Pytorch, we first built the radiomic and genetic signature. Next, we passed the CT images and gene data into the trained ResNet18 and Random Forest and then we sum the output probabilities of two models with a weight of 3:7 to obtain the classification probability of the fusion model. Results: The signature successfully predict sensitivity to anti-EGFR therapy (The area under the curve (AUC) of the radiomic signature: 0.75; the genetic signature: 0.81; the fusion signature: 0.86) but failed with chemotherapy (The fusion signature: 0.54). In cetuximab-containing sets, the fusion signature outperformed existing biomarkers for detection of treatment sensitivity (OR = 17.9, 95% CI 3.22–154.31, P = 0.003) and was strongly associated with progression free survival (mPFS: 12.0 vs. 15.0 months, HR: 0.44, 95% CI 0.20–0.99, P = 0.047). Conclusions: The multi-omics signature can serve as an intermediate surrogate marker of anti-EGFR treatment sensitivity and survival. The signature outperformed known biomarkers in providing an early prediction of treatment sensitivity and could be used to RAS wild type mCRC treatment decisions.

Weakly supervised label propagation algorithm classifies lung cancer imaging subtypes

Aiming at the problems of long time, high cost, invasive sampling damage, and easy emergence of drug resistance in lung cancer gene detection, a reliable and non-invasive prognostic method is proposed. Under the guidance of weakly supervised learning, deep metric learning and graph clustering methods are used to learn higher-level abstract features in CT imaging features. The unlabeled data is dynamically updated through the k-nearest label update strategy, and the unlabeled data is transformed into weak label data and continue to update the process of strong label data to optimize the clustering results and establish a classification model for predicting new subtypes of lung cancer imaging. Five imaging subtypes are confirmed on the lung cancer dataset containing CT, clinical and genetic information downloaded from the TCIA lung cancer database. The successful establishment of the new model has a significant accuracy rate for subtype classification (ACC = 0.9793), and the use of CT sequence images, gene expression, DNA methylation and gene mutation data from the cooperative hospital in Shanxi Province proves the biomedical value of this method. The proposed method also can comprehensively evaluate intratumoral heterogeneity based on the correlation between the final lung CT imaging features and specific molecular subtypes.

Difference in CT RT-PCR Value of SARS-COV-2 on VTM Non-inactivated with VTM Inavtivated

Nasopharyngeal swab collection for SARS-CoV-2 examination by RT-PCR requires Viral Transport Medium (VTM) using VTM non-activated and inactivated. This study determined the difference in CT values for SARS CoV-2 RT-PCR examination in non-activated VTM and inactivated VTM. This study is a comparative analytical study with a cross-sectional method using 20 confirmed positive samples for SARS-CoV-2 at RSU. Dr. Suyoto was analyzed by the T-Independent test (N gene) and Mann-Whitney test (ORF1ab gene) using SPSS with α=0.05. The results showed that VTM non-inactivated had a mean CT value of the N gene 33.56 ± 1.39 and the ORF1ab gene 35.4 ± 1.94, while VTM inactivated had an average CT value of 32.24 ± 1.44 for the N and ORF1ab gene 33.93 ± 3.22. Statistical analysis was tested by the T-independent test (N gene), and the Mann Whitney test (ORF1ab gene) between the use of VTM non-inactivated and VTM inactivated in the SARS CoV-2 RT-PCR examination, obtained p-value 0.05 with a mean difference the results of Ct gene n (p=0.006) and gene ORF1ab (p=0.028). This indicated a difference in the mean C CT value of the SARS CoV-2 RT-PCR examination in non-activated VTM and inactivated VTM.

Difference in CT RT-PCR Value of SARS-COV-2 on VTM Non-inactivated with VTM Inavtivated

Nasopharyngeal swab collection for SARS-CoV-2 examination by RT-PCR requires Viral Transport Medium (VTM) using VTM non-activated and inactivated. This study determined the difference in CT values for SARS CoV-2 RT-PCR examination in non-activated VTM and inactivated VTM. This study is a comparative analytical study with a cross-sectional method using 20 confirmed positive samples for SARS-CoV-2 at RSU. Dr. Suyoto was analyzed by the T-Independent test (N gene) and Mann-Whitney test (ORF1ab gene) using SPSS with α=0.05. The results showed that VTM non-inactivated had a mean CT value of the N gene 33.56 ± 1.39 and the ORF1ab gene 35.4 ± 1.94, while VTM inactivated had an average CT value of 32.24 ± 1.44 for the N and ORF1ab gene 33.93 ± 3.22. Statistical analysis was tested by the T-independent test (N gene), and the Mann Whitney test (ORF1ab gene) between the use of VTM non-inactivated and VTM inactivated in the SARS CoV-2 RT-PCR examination, obtained p-value 0.05 with a mean difference the results of Ct gene n (p=0.006) and gene ORF1ab (p=0.028). This indicated a difference in the mean C CT value of the SARS CoV-2 RT-PCR examination in non-activated VTM and inactivated VTM.

Integrating Radiomics with Genomics for Non-Small Cell Lung Cancer Survival Analysis.

Purpose The objectives of our study were to assess the association of radiological imaging and gene expression with patient outcomes in non-small cell lung cancer (NSCLC) and construct a nomogram by combining selected radiomic, genomic, and clinical risk factors to improve the performance of the risk model. Methods A total of 116 cases of NSCLC with CT images, gene expression, and clinical factors were studied, wherein 87 patients were used as the training cohort, and 29 patients were used as an independent testing cohort. Handcrafted radiomic features and deep-learning genomic features were extracted and selected from CT images and gene expression analysis, respectively. Two risk scores were calculated through Cox regression models for each patient based on radiomic features and genomic features to predict overall survival (OS). Finally, a fusion survival model was constructed by incorporating these two risk scores and clinical factors. Results The fusion model that combined CT images, gene expression data, and clinical factors effectively stratified patients into low- and high-risk groups. The C-indexes for OS prediction were 0.85 and 0.736 in the training and testing cohorts, respectively, which was better than that based on unimodal data. Conclusions Combining radiomics and genomics can effectively improve OS prediction for NSCLC patients.

Abstract P5-12-12: The role of a cancer testis-antigen in regulating tumor growth and oncogenic pathways in triple-negative breast cancer

Abstract Breast cancer is the second leading cause of cancer mortality in women after lung cancer; however, it is the primary cause of death among Hispanic women. About 10-20% of breast cancers are basal (triple-negative) subtype at the time of diagnosis, and they do not respond well to treatment regimens due to a lack of specific targets. Triple-negative breast cancer is a deadly and very aggressive tumor type associated with poor prognosis compared to other molecular subtypes of breast cancer, especially among Hispanic women. Thus, identifying novel molecules with prognostic and therapeutic value is critical to treat this ever-evolving disease. Numerous studies suggest that genes transcribed from chromosome X (X-linked genes) are implicated in cancers. The expression of these genes is tightly regulated and restricted to immune-privileged organs; however, many of them escape regulation and become aberrantly expressed in tumors.Interestingly, our genomic analysis suggests that several newly annotated X-linked genes are cancer testis-antigens (CT genes) that are highly antigenic and are located at regions previously considered to be gene deserts in the human genome. To date, very minimal is known about their expression and role in triple-negative breast cancer. In this regard, we used an integrated genomic approach to identify testis-tissue-specific genes that are differentially expressed in triple-negative breast cancer. Further, we identified a highly immunogenic cancer-testis gene by incorporating cutting-edge technology-driven (Global Run-On Sequencing) gene expression analysis. Mechanistically, by using cell-, mouse-based, and genomic approaches, we have found that candidate CT gene modulates gene expression, immune response, and tumor growth in triple-negative breast cancer. Hence, it has the potential to change the way triple-negative breast cancer is diagnosed and treated. S.S.G. is supported by a First-time Faculty Recruitment Award from the Cancer Prevention and Research Institute of Texas (CPRIT; RR170020). S.S.G. is also supported by a grant from Lizanell and Colbert Coldwell foundation. Citation Format: Melina J Sedano, Alana L Harrison, Ine le, Shrikanth S Gadad. The role of a cancer testis-antigen in regulating tumor growth and oncogenic pathways in triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-12.

Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis

ObjectivesImportations of novel variants of concern (VOC), particularly B.1.617.2, have become the impetus behind recent outbreaks of SARS-CoV-2. Concerns around the impact on vaccine effectiveness, transmissibility and severity are now...

Dendrimer-modified gold nanorods as a platform for combinational gene therapy and photothermal therapy of tumors

BackgroundThe exploitation of novel nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is challenging for tumor theranostics.MethodsWe synthesized dendrimer-modified gold nanorods for combinational gene therapy and photothermal therapy (PTT) of colon cancer. Poly(amidoamine) dendrimers (PAMAM, G3) grafted gold nanorods were modified with GX1 peptide (a cyclic 7-mer peptide, CGNSNPKSC). The obtained Au NR@PAMAM-GX1 are proposed as a gene delivery vector to gene (FAM172A, regulates the proliferation and apoptosis of colon cancer cells) for the combination of photothermal therapy (PTT) and gene therapy of Colon cancer cells (HCT-8 cells). In addition, the CT imaging function of Au NR can provide imaging evidence for the diagnosis of colon cancer.ResultsThe results display that Au NR@PAMAM-GX1 can specifically deliver FAM172A to cancer cells with excellent transfection efficiency. The HCT-8 cells treated with the Au NR@PAMAM-GX1/FAM172A under laser irradiation have a viability of 20.45%, which is much lower than the survival rate of other single-mode PTT treatment or single-mode gene therapy. Furthermore, animal experiment results confirm that Au NR@PAMAM-GX1/FAM172A complexes can achieve tumor thermal imaging, targeted CT imaging, PTT and gene therapy after tail vein injection.ConclusionOur findings demonstrate that the synthesized Au NR@PAMAM-GX1 offer a facile platform to exert antitumor and improve the diagnostic level of tumor.

Defining the Balance between the Expression of Procoagulant, Anticoagulant and Angiogenic Molecules in Myeloma Plasma Cells

Introduction: Multiple myeloma is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells in the bone marrow and other tissues. This disease significantly increases the risk of venous thromboembolic disorders. The interplay between Myeloma Plasma Cells (MPCs) with coagulation and angiogenesis is currently under investigation. It has been shown that MPCs promotes angiogenesis through VEGF expression. Whether MPCs express procoagulant and/or anticoagulant proteins remains to be shown.Aim: To determine the expression of tissue factor (TF), tissue factor pathway inhibitor 1 (TFPI 1), tissue factor pathway inhibitor 2 (TFPI 2), vascular endothelial growth factor (VEGF-A) and thrombomodulin (TM) by MPCs.Methods: Human MPCs (RPMI 8226) and human umbilical vein endothelial cells (HUVECs) that were used as control were cultured according to standard procedures. Total RNA was extracted and reversely transcribed as previously described. Briefly, 1 μg cDNA was PCR amplified using the Go TAq® qPCRMaster mix (Promega) and the Mx3000P qPCR system according to the manufacturer's protocol. Quantitative RT-PCR was used to measure the relative mRNA levels using TaqMan assays for VEGF-A, TFPI 1, TFPI 2, TF or TM (Sigma Aldrich). Ct values were normalized against the endogenous control B-Actine (from Sigma Aldrich).Relative mRNA expression was calculated using the comparative threshold method (1/PUISSANCE (2 (Ct (gene)-Ct (endogenous control))).Results: MPCs exhibited 4-fold higher TF expression compared to HUVECs but significantly lower expression of TFPI1 and TFPI2. For both MPCs and HUVECs, the expression of TFPI 1 was more pronounced compared to the expression of TF gene. Interestingly, MPCs showed lower expression of TFPI 2 compared to TF. Therefore, the TF/TFPI 1 ratio was higher in MPCs, reflecting a potentially increased TF activity compared to HUVECs. MPCs and HUVECs expressed comparable levels of TM. Finally, VEGF expression was significantly higher in the MPCs as compared to HUVECs. Results are summarized in Table 1.Conclusions. Plasmocytes from human multiple myeloma cells are characterized by a marked proangiogenic potential driven by high gene expression of VEGF which is accompanied by increased expression of TF. However, TF expression seems to be at least partially compensated by increased expression of TFPIs leading to the assumption that the TF-dependent procoagulant properties of plasmocytes are restricted by a balanced increase in TFPI. These data indicate that TF expression by myeloma cells may be associated with cell proliferation rather than a procoagulant [Display omitted] DisclosuresGarderet:Amgen: Honoraria; Takeda: Honoraria.

A Systematic Review of Lymphangioleiomyomatosis on Diagnosis and Molecular Mechanism.

Objective Lymphangioleiomyomatosis (LAM) is a rare low-grade metastatic tumor; however, LAM patients were always found in young age with difficulty for diagnosis. Our study is aimed at observing the clinical characteristics of patients with lymphangiomatosis, including the clinical manifestations, imaging findings, histopathological features, and immunophenotype. Methods We did a systematic review on LAM/PLAM cases, especially on male cases, and collected the clinical features and molecular mechanisms of PLAM based on previous findings. Results Diagnosis criteria were summarized by combining CT scans, MRI, immunohistochemistry results, and gene sequencing results for effectively distinguishing between PLAM and similar diseases. Moreover, our study illustrated the molecular mechanism of PLAM as well as the signaling pathway involved in the disease initials. In addition, a male case was reported with differential diagnosis on the clinical manifestations, microscopic features, immunophenotypes, and genotypes. Conclusion Our review will definitely improve the understanding of diagnosis and treatment in PLAM cases.

Association of methylenetetrahydrofolate reductase C677T CT gene polymorphism with a non-dipping blood pressure pattern in morbidly obese patients

Association of methylenetetrahydrofolate reductase C677T CT gene polymorphism with a non-dipping blood pressure pattern in morbidly obese patients

Cancer Testis Antigens and Immunotherapy: A new Dawn

Immunotherapy for cancer has been recognized as the fourth therapeutic method after surgery, radiotherapy and chemotherapy, which can prevent postoperative metastasis and recurrence and reduce or even eliminate the toxic and side effects of chemoradiotherapy. The development of successful immunotherapy strategies need to use cancer antigens which can be identified by the host’s immune system. This method’s ability in causing antitumor immune response has been fully proved, but it also faces enormous risks and challenges, as finding the highly efficient and specific tumor markers is very difficult. Cancer-testis antigens(CTA) are a special kind of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. The immune privileged status of CTA gives tumor specificity and makes it an ideal candidate for targeted immunotherapy biomarkers. Here, we briefly review the research history, expression characteristics of CTA, molecular mechanisms of CT gene, and the bright future of immunotherapy in cancer treatment.

Association of arterial hypertension gene polymorphisms with the risk of sudden cardiac death in young people

Abstract. The frequency of occurrence of arterial hypertension genes in individuals at risk of sudden cardiac death was studied. The relationship between risk factors for sudden cardiac death and the presence of polymorphisms of arterial hypertension genes was revealed. There was a high incidence of homozygous risk variants AGTR2 AA and CYP11B2 TT-polymorphisms responsible for the development of left ventricular hypertrophy, including in young individuals. A correlation was found between deaths in close relatives under 50 years of age and the presence of polymorphisms in the CYP11B2 344 CT gene in young people at risk of sudden cardiac death. We have obtained data indicating the feasibility of conducting a study of the polymorphism of the CYP11B2 gene in the presence of a risk of sudden cardiac death. A direct correlation was found between the presence of fatal outcomes in relatives under 50 years of age by the mechanism of sudden cardiac death and the number of homozygous variants of arterial hypertension genes. Mathematical models for predicting the presence of polymorphisms in genes responsible for the possibility of arterial hypertension are constructed. Among the constructed mathematical models, the most informative were models for detecting carriers of mutations in the genes ADD1 1378 GT, CYP11B2 344 CT and NOS3 894 GT. The expediency of the analysis to search for mutations of arterial hypertension genes, especially in the CYP11B2 344 CT gene, for the possibility of earlier and more intensive preventive measures in young people is shown. The data obtained indicate that there are relationships between the risk of sudden cardiac death, some known predictors of its occurrence, and the genes for arterial hypertension.

Vitamin D receptor Fok1 polymorphism and invasive ovarian carcinoma risk - A case-control study.

• Tubal ligation is protective against ovarian cancer. • Vitamin D deficiency is significantly associated with ovarian cancer. • TT genotype is not seen in our study population. • CT gene polymorphism is found to be associated with ovarian cancer. • Vitamin D deficiency and CT polymorphism have independent effects.

PATH-63. TRANSCRIPTIONAL SIGNATURES IN HISTOLOGIC STRUCTURES WITHIN GLIOBLASTOMA TUMORS MAY PREDICT PERSONALIZED TREATMENT SENSITIVITY AND SURVIVAL

Abstract OBJECTIVE Personalized treatment strategies in Glioblastoma multiforme (GBM) has been hampered by intra-tumoral heterogeneity. The goals of this study were to (1) determine the impact of intra-tumoral heterogeneity on established predictive and prognostic transcriptional signatures in human GBM, and (2) develop methods to mitigate the impact of tissue heterogeneity on transcriptomic-based patient stratification. METHODS We analyzed transcriptional profiles of GBM histological structures from the open-source Ivy Glioblastoma Atlas Project. To generate these data, infiltrative tumor, leading edge, cellular tumor [CT], perinecrotic zones, pseudopalisading cells, hyperplastic blood vessels and microvascular proliferation were microdissected from 34 newly diagnosed GBM and underwent RNA sequencing. Data from The Cancer Genome Atlas were used for validation. Principle component analysis, network analysis and gene set enrichment analysis were used to probe gene expression patterns. RESULTS Distinct biological networks were enriched in each tumor histological structure. Classification of patients into GBM molecular subtypes varied based on the structure assessed, with many patients classified as every subtype depending on the structure analyzed. Using only CT to classify subtypes, we identified biologically unique patterns suggesting that proneural and mesenchymal tumors may be more sensitive to chemoradiotherapy and immunotherapy, respectively. Survival outcome predicted by an established multigene panel was confounded by histologic structure. Utilizing CT transcriptomics we developed a novel survival prediction gene signature that identified the highest-risk GBM patients in both CT and bulk tissue gene expression profiles. CONCLUSIONS Histologic structures contribute to intra-tumoral heterogeneity in GBM. Using mixed-structure biopsy samples could incorrectly subtype tumors and produce invalid patient stratification. Limiting transcriptomic analysis to the CT allowed us to develop a new survival prediction gene signature that appears accurate even in mixed tissue samples. The biological patterns uncovered in the subtypes and risk-stratified groups have important implications for guiding the development of precision medicine in GBM.