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1.
Cell Physiol Biochem ; 45(4): 1444-1454, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466793

RESUMO

BACKGROUND/AIMS: Colonoscopy screening has been accepted broadly to evaluate the risk and incidence of colorectal cancer (CRC) during health examination in outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy may limit its application and the compliance of patients. Thus, more reliable and convenient diagnostic methods are necessary for CRC screening. Genome instability, especially copy-number variation (CNV), is a hallmark of cancer and has been proved to have potential in clinical application. METHODS: We determined the diagnostic potential of chromosomal CNV at the arm level by whole-genome sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm level CNV was determined and the consistence of arm-level CNV between plasma and tissue was further analyzed. Two methods including regular z score and trained Support Vector Machine (SVM) classifier were applied for detection of colorectal cancer. RESULTS: In plasma samples of CRC patients, the most frequent deletions were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level alterations detected in plasma were also observed in tumor tissues. We showed that the specificity of regular z score analysis for the detection of colorectal cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32). Applying a trained SVM classifier (n = 40 in trained group) as the standard to detect colorectal cancer relevance ratio in the test samples (n = 30), a sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally reached. Furthermore, all five early CRC patients in stages I and II were successfully detected. CONCLUSION: Trained SVM classifier based on arm-level CNVs can be used as a promising method to screen early-stage CRC.


Assuntos
Cromossomos/metabolismo , Neoplasias Colorretais/diagnóstico , DNA/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Área Sob a Curva , Estudos de Casos e Controles , Cromossomos/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , DNA/genética , DNA/metabolismo , Variações do Número de Cópias de DNA , Detecção Precoce de Câncer , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Sensibilidade e Especificidade , Análise de Sequência de DNA , Máquina de Vetores de Suporte , Adulto Jovem
2.
Plant Sci ; 181(6): 652-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21958707

RESUMO

Sweet sorghum (Sorghum bicolor (Linn.) Moench) has promise as a bioenergy feedstock in China and other countries for its use in the production of ethanol as the result of its high fermentable sugar accumulation in stems. To boost biofuel production and extend its range, we seek to improve its stress tolerance. Proline acts as an osmolyte that accumulates when plants are subjected to abiotic stress. P5CS (Δ1-pyrroline-5-carboxylate synthetase) is a key regulatory enzyme that plays a crucial role in proline biosynthesis. We isolated two closely related P5CS genes from sweet sorghum, designated SbP5CS1 (GenBank accession number: GQ377719) and SbP5CS2 (GenBank accession number: GQ377720), which are located on chromosome 3 and 9 and encode 729 and 716 amino acid polypeptides, respectively. The homology between the two sweet sorghum P5CS genes was 76%. Promoter analysis of the two P5CS genes revealed that both sequences not only contained the expected cis regulatory regions such as TATA and CAAT boxes, but also had many stress response elements. Expression analysis revealed that SbP5CS1 and SbP5CS2 transcripts were up-regulated after treatment of 10-day-old seedlings of sweet sorghum with drought, salt (250mM NaCl) and MeJA (10µM). The expression levels of the both SbP5CS genes were significantly increased after 3-day drought stress. Under high salt treatment, peak SbP5CS1 expression was detected at 4h and 8h for SbP5CS2 in roots, while the trends of expression were nearly identical in leaves. In contrast, under drought and high salt stress, the up-regulated expression of SbP5CS1 was higher than that of SbP5CS2. When the seedlings were exposed to MeJA, rapid transcript induction of SbP5CS1 was detected at 2h in leaves, and the SbP5CS2 expression level increase was detected at 4h post-treatment. SbP5CS1 and SbP5CS2 also show different temporal and spatial expression patterns. SbP5CS2 gene was ubiquitously expressed whereas SbP5CS1 was mainly expressed in mature vegetative and reproductive organs. Proline concentration increased after stress application and was correlated with SbP5CS expression. Our results suggest that the SbP5CS1 and SbP5CS2 are stress inducible genes but might play non-redundant roles in plant development. The two genes could have the potential to be used in improving stress tolerance of sweet sorghum and other bioenergy feedstocks.


Assuntos
Ornitina-Oxo-Ácido Transaminase/genética , Sorghum/genética , Estresse Fisiológico , Acetatos , Sequência de Aminoácidos , Biocombustíveis , Ciclopentanos , Secas , Expressão Gênica , Dados de Sequência Molecular , Ornitina-Oxo-Ácido Transaminase/metabolismo , Oxilipinas , Filogenia , Reguladores de Crescimento de Plantas , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Prolina/metabolismo , Regiões Promotoras Genéticas , Salinidade , Plântula/metabolismo , Análise de Sequência de DNA , Sorghum/enzimologia , Transcriptoma , Regulação para Cima
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