• KIPS Transactions on Software and Data Engineering
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• v.10 no.12
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• pp.547-554
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• 2021

Cancer patients can have different kinds of cancer driver genes, and identification of these patient-specific cancer driver genes is an important step in the development of personalized cancer treatment and drug development. Several bioinformatic methods have been proposed for this purpose, but there is room for improvement in terms of accuracy. In this paper, we propose NPD (Network based Patient-specific Driver gene identification) for identifying patient-specific cancer driver genes. NPD consists of three steps, constructing a patient-specific gene network, applying the modified PageRank algorithm to assign scores to genes, and identifying cancer driver genes through a score comparison method. We applied NPD on six cancer types of TCGA data, and found that NPD showed generally higher F1 score compared to existing patient-specific cancer driver gene identification methods.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3377-3380
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• 2016

The proportion of lung cancer patients under 50 years old is small at approximately 5-10%, but as with patients older than 50, the number is on the rise. Although lung cancer treatment strategies have undergone extensive transformation in recent years based on the presence or absence of oncogenic driver mutations, there are few reports regarding these mutations in the young or the relationship between clinical setting and prognosis. Therefore, we conducted a study of clinical features in 36 patients under the age of 50 who were diagnosed with primary lung cancer from October 2008 to November 2015. The 22 patients in stages I through III A underwent operations, and all 17 whose lung cancer were detected through screening were candidates for surgery. Gene analysis was conducted for 26 (72.2%); 10 (38.5%) were positive for EGFR gene mutations, and ALK gene translocation was present in 4 (15.4%). In stage IV patients, the median progression free survival (PFS) in the ALK translocation positive and negative patients was 518 days and 130 days, respectively, and the median overall survival (OS) was not reached and 280 days, respectively. A trend toward extended PFS (p=0.203) and OS (p=0.056) was observed in patients positive for ALK translocation. We must strive for early detection by increasing screening rates and evaluate oncogenic driver mutations important for prognosis of lung cancer in the young.

• BMB Reports
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• v.51 no.2
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• pp.57-58
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• 2018

An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4147-4156
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• 2015

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.49 no.2
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• pp.148-153
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• 2004

The Hessian fly, Mayetiola destructor (Say), is known to be one of the major insect herbivores of wheat worldwide. In order to provide molecular events on interactions of the NIL with H21 and larvae of Hessian fly biotype L, the TaCR1 gene, Triticum aestivum cytokinin repressed 1, was isolated through the suppression subtractive hybridization, which was constructed using stems of the NIL with H21 at 6 days after infestation as tester and stems of the recurrent parent Coker797 without H21 at 6 days after infestation as driver. Transcript levels of TaCR1 mRNA in the NIL with H21 were highest at 6 days after infestation but in the Coker797 without H21 until 8 days were similar with those of non-infested plants. Expression of the TaCR1 gene was decreased at early time and then recovered after wounding or $H_2O$$_2$ treatment as well as 6-BAP treatment. Transcripts levels of the TaCR1 gene was changed after MeJA, SA, ethephone, or ABA treatment. In drought treatment, the TaCRl gene were increased at early stage of stress and then decreased at late stage. Expression of the TaCRl gene was continued to decrease through 24 h in the cold treatment. Although the TaCRl gene is increased through infestation in NIL with H21, further study was required to elucidate a role on resistance against larvae of Hessian fly. However, the TaCR1 gene could be used as marker gene on response of plants against abiotic stresses as well as application of plants with several hormones.

• Genomics & Informatics
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• v.10 no.1
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• pp.33-39
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• 2012

High-throughput genomic technologies (HGTs), including next-generation DNA sequencing (NGS), microarray, and serial analysis of gene expression (SAGE), have become effective experimental tools for cancer genomics to identify cancer-associated somatic genomic alterations and genes. The main hurdle in cancer genomics is to identify the real causative mutations or genes out of many candidates from an HGT-based cancer genomic analysis. One useful approach is to refer to known cancer genes and associated information. The list of known cancer genes can be used to determine candidates of cancer driver mutations, while cancer gene-related information, including gene expression, protein-protein interaction, and pathways, can be useful for scoring novel candidates. Some cancer gene or mutation databases exist for this purpose, but few specialized tools exist for an automated analysis of a long gene list from an HGT-based cancer genomic analysis. This report presents a new web-accessible bioinformatic tool, called CaGe, a cancer genome annotation system for the assessment of candidates of cancer genes from HGT-based cancer genomics. The tool provides users with information on cancer-related genes, mutations, pathways, and associated annotations through annotation and browsing functions. With this tool, researchers can classify their candidate genes from cancer genome studies into either previously reported or novel categories of cancer genes and gain insight into underlying carcinogenic mechanisms through a pathway analysis. We show the usefulness of CaGe by assessing its performance in annotating somatic mutations from a published small cell lung cancer study.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.17-24
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• 2010

In the antral follicle phase, several layers of cumulus cells surround the oocyte and play an important support and regulation role in oocyte development and maturation via intercellular communications and interactions between oocytes and cumulus cells. However, information on stage specific gene expression in swine during the phase is not well understood. To investigate the function of cumulus cells during in vitro maturation of porcine oocytes and gene expression, suppression subtractive hybridization (SSH) was performed to screen genes that were differentially expressed between cumulus-oocyte complexes (COCs) and naked oocytes (NOs). Utilizing mRNAs from in vitro maturation oocytes, a SSH cDNA library from COCs as the tester and NOs as the driver was constructed. The SSH cDNA library was then screened using dot blot analysis. Results showed that a total of 70 clones randomly selected from the library were differentially expressed. Among these, 41 exhibited high homology to known genes and 11 were novel expressed sequences tags (ESTs). Four differentially expressed genes, including bfgf, sprouty 2, egr and btc, were further studied by real time quantitative PCR; results confirmed an increased expression of respective mRNA in COCs compared with NOs, which suggests that these factors may play an important role in oocyte development and maturation.

• BMB Reports
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• v.53 no.10
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• pp.521-526
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• 2020

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues.

• Plant Biotechnology Reports
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• v.3 no.4
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• pp.325-331
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• 2009

To efficiently express a gene of interest in transgenic plants, the choice of promoter is a crucial factor as it directly affects the expression of the transgene that will yield the desired phenotype. The Arabidopsis ${\beta}-carotene$ hydroxylase 1 gene (AtBch1) shows constitutive and ubiquitous expression and was thus selected as one of best candidates for constitutive promoter analysis by both in silico northern blotting and semi-quantitative RT-PCR analysis. To investigate AtBch1 promoter activity, the 1,981-bp 5'-upstream region of this gene was fused with ${\beta}-glucuronidase$ (GUS) and transformed into Arabidopsis. Through the molecular characterization of transgenic leaf tissues, the AtBch1 promoter generated strong activity that drives 1.8- and 2-fold higher GUS expression than the cauliflower mosaic virus 35S (35S) promoter at the transcriptional and translational levels, respectively. Furthermore, the GUS enzyme activity driven by the AtBch1 promoter was 2.8-fold higher than that produced by the 35S promoter. By histochemical GUS staining, the ubiquitous expression of the AtBch1 promoter was observed in all tissues of Arabidopsis. Semi-quantitative RT-PCR analysis with different tissues further showed that this promoter serves as a strong constitutive driver of transgene expression in dicot plants.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.