• Title/Summary/Keyword: Biomarkers

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Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

  • Wang, Da-Guang;Chen, Guang;Wen, Xiao-Yu;Wang, Dan;Cheng, Zhi-Hua;Sun, Si-Qiao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1361-1365
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    • 2015
  • Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.

Could the Breast Prognostic Biomarker Status Change During Disease Progression? An Immunohistochemical Comparison between Primary Tumors and Synchronous Nodal Metastasis

  • El Nemr Esmail, Reham Shehab;El Farouk Abdel-Salam, Lubna Omer;Abd El Ellah, Mohammed M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4317-4321
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    • 2015
  • Background: Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression. Materials and Methods: 60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples Results: 48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was statistically significant. On the other hand, 70% of the cases showed concordant Her2 results between the primary tumors and the nodal deposits, 30% showed discordant results and the difference was significant. Conclusions: The study indicated that the discordance in ER and PR receptor expression between the primary breast tumor and their nodal metastasis may be significant. The possible switch in the biomarker status during the disease progression is worth noting and may change the patient therapeutic planning. So, whether the treatment selection should be based on biomarkers in the lymph node is a topic for further studies and future clinical trials.

Comparison of Serum Tumor Associated Material (TAM) with Conventional Biomarkers in Cancer Patients

  • Shu, Jian;Li, Cheng-Guang;Liu, Yang-Chen;Yan, Xiao-Chun;Xu, Xu;Huang, Xin-En;Cao, Jie;Li, Ying;Lu, Yan-Yan;Wu, Xue-Yan;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2399-2403
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    • 2012
  • Objective: To compare expression level of serum tumor associated materials (TAM) with several conventional serum tumor biomarkers, eg., carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein(AFP), in selected solid tumors. Methods: Patients diagnosed histologically or cytologically with liver, breast, esophageal, gastric, colorectal or pancreatic cancers were enrolled into this study. After diagnosis, the level of TAM was determined by chemical colorimetry, and levels of conventional tumor markers was measured by chemiluminescence methods. Results: A total of 560 patients were enrolled into this study. No statistically significant difference was detected in TAM and the above mentioned tumor biomarkers in terms of their positivity and negativity ( P>0. 05). Conclusions: Detection of TAM in liver, breast, esophageal, gastric, colorectal, and pancreatic cancer patients demonstrates a good accordance with CEA, CA199, CA153, and AFP, thus suggesting that further study is warranted to verify whether TAM could be a surrogate for these conventional biomarkers.

Identification of Gene-based Potential Biomarkers for Cephalexin-induced Nephrotoxicity in Mice

  • Park, Han-Jin;Oh, Jung-Hwa;Hwang, Ji-Yoon;Lim, Jung-Sun;Jeong, Sun-Young;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.2 no.3
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    • pp.193-201
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    • 2006
  • Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

A Correlation Study of Pattern Identification Instrument and Biomarkers for Polycystic Ovary Syndrome (다낭성난소증후군 변증도구와 생체지표 간의 상관성 연구)

  • Park, Eun-Ji;Baek, Seon-Eun;Kang, Byoung-Kab;Yoo, Jeong-Eun;Jung, In-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.31 no.3
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    • pp.33-49
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    • 2018
  • Objectives: The purpose of this study was to investigate the correlation between Pattern identification instrument and biomarkers in polycystic ovary syndrome patients. Methods: Pattern identification instrument questionnaire, Sasang constitutional test, body composition test, pulse analyzing test, laboratory test were performed and the results were analyzed. Correlation analysis was performed between pattern identification and laboratory test results. Results: Testosterone, SHBG, $17{\alpha}$-OH-progesterone, AMH were highest in the Kidney-Yang Deficiency (腎陽虛) group. LH, FSH, LH/FSH ratio were the highest in the Endogenous Heat due to Yin Deficiency (陰虛內熱) group. DHEA-S was the highest in the Dampness-Heat in Liver Meridian (肝經濕熱) group. E2, Prolactin, Cholesterol, Triglyceride, HDL-Cholesterol, LDL-Cholesterol, Glucose (FBS), Insulin, HOMA-IR ratio, HbA1c were the highest in the Phlegm-Dampness (痰濕) group. Conclusions: In this study, we obtained basic data analyzing the correlation between pattern identification instrument and biomarkers in polycystic ovary syndrome patients. If further studies are performed, we expect to be able to obtain clues to study the mechanism of polycystic ovary syndrome.

Food web structure in a $Salix$ $subfragilis$ dominated wetland in Hangang estuary using stable isotopes and fatty acid biomarkers

  • Han, Dong-Uk;Yang, Dong-Woo;Lee, Eun-Joo;Park, Sang-Kyu
    • Animal cells and systems
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    • v.16 no.2
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    • pp.162-171
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    • 2012
  • We investigated food webs of a $Salix$ $subfragilis$-dominated wetland in the Janghang wetland in the Hangang estuary, which is very close to the Demilitarized Zone, along the west coast of Korea. Our study focused on understanding sesarmine crab ($Sesarma$ $dehaani$)-related food webs in a $S.$ $subfragilis$ forest. For our study, we used carbon and nitrogen stable isotopes and fatty acid biomarkers. We collected samples of plants, animals, and detrital sediment from four quadrats ($5{\times}5m^2$) set in the $S.$ $subfragilis$ community. Samples were collected from September 2006 to June 2009, except during the winter hibernation period of $S.$ $dehaani$. In the wet season, the sediment showed relatively high ${\delta}^{13}C$ and low ${\delta}^{15}N$ signatures compared with relatively low ${\delta}13C$ and high ${\delta}15N$ signatures in the dry season. Mature $S.$ $dehaani$ appeared to feed on fresh leaves and other carbon sources, such as immature individuals or fish, in addition to detrital sediment, which appeared to be the main carbon source for immature crabs. Principal component analysis of fatty acid biomarkers of $S.$ $dehaani$ showed a clear difference between immature individuals (10-30 mm) and mature ones (larger than 30 mm), indicating that the main food source for immature crabs was detrital sediment, whereas mature crabs foraged plants in addition to consuming detrital sediment. On the basis of our results from stable isotope and fatty acid analyses, mature $S.$ $dehaani$ appeared to feed on detrital sediment and fresh leaves of $S.$ $subfragilis$ in summer in addition to engaging in cannibalism of immature individuals.

Noninvasive Biomarker for Predicting Treatment Response to Concurrent Chemoradiotherapy in Patients with Hepatocellular Carcinoma

  • Chung, Yong Eun;Park, Jun Yong;Choi, Jin-Young;Kim, Myeong-Jin;Park, Mi-suk;Seong, Jinsil
    • Investigative Magnetic Resonance Imaging
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    • v.23 no.4
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    • pp.351-360
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    • 2019
  • Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.

Novel Biomarkers for Prediction of Response to Preoperative Systemic Therapies in Gastric Cancer

  • Cavaliere, Alessandro;Merz, Valeria;Casalino, Simona;Zecchetto, Camilla;Simionato, Francesca;Salt, Hayley Louise;Contarelli, Serena;Santoro, Raffaela;Melisi, Davide
    • Journal of Gastric Cancer
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    • v.19 no.4
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    • pp.375-392
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    • 2019
  • Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

Influence of Postconceptional Age on the Renal Biomarkers in Very-Low-Birth-Weight Infants

  • Lee, Ro Sie;Shin, So Young;Jung, Won Ho;Park, Jae Hyun
    • Neonatal Medicine
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    • v.28 no.2
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    • pp.65-71
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    • 2021
  • Purpose: We investigated whether consecutive levels of new emerging renal biomarkers, including serum cystatin C (CysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL)/creatinine (Cr) ratio, were affected by postconceptional age in very-low-birth-weight (VLBW) infants. Methods: Repeatedly measured samples for each infant were divided into four groups according to postnatal age: at birth (stage I), 3 to 7 days postnatally (stage II), 8 to 28 days postnatally (stage III), and >28 days postnatally (stage IV). The association between renal biomarkers and postconceptional age was assessed using Pearson's correlation coefficient, and the mean values of renal biomarkers in the four stages were compared using repeated-measures analysis of variance. Results: For samples measured at birth, serum CysC (r=-0.358, P=0.032) and urinary NGAL/Cr ratio (r=-0.522, P=0.001) were negatively correlated with gestational age, whereas serum Cr (r=0.148, P=0.390) was not. In addition, for all samples measured, serum CysC (r=-0.209, P=0.012), urinary NGAL/Cr ratio (r=-0.536, P<0.001), and serum Cr (r=-0.311, P<0.001) were negatively correlated with postconceptional age. Compared with the mean values of the postnatal age-specific stages, serum CysC showed no significant differences in any of the four stages. However, the urinary NGAL/Cr ratio in stage IV was significantly different from those in stages I to III. Conclusion: Although urinary NGAL/Cr ratio and serum CysC were negatively correlated with postconceptional age considering renal development, serum CysC showed no significant differences in any of the four postnatal age-specific stages. Urinary NGAL/Cr ratio at >28 days postnatally seems to be more affected by postconceptional age than serum CysC in VLBW infants.

Differences in Environmental Tobacco Smoke Exposure between Self-reporting and Cotinine Test: The Application of Biomarkers (자가응답과 코티닌 측정에 의한 간접흡연 노출률 비교: 생체지표 활용의 정책적 필요성)

  • Park, Myung-Bae;Sim, Boram
    • Health Policy and Management
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    • v.30 no.4
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    • pp.505-512
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    • 2020
  • Background: In monitoring exposure to environmental smoke (ETS), biomarkers can overcome the subjectivity and inaccuracy of self-reporting measurements, and have the advantage of reflecting ETS exposure in all places. This study aims to evaluate the effectiveness of ETS exposure measurement using biomarkers such as urine cotinine. Methods: This study used the Korea National Health and Nutrition Survey data from 2009 to 2018. A total of 28,574 non-smokers with urine cotinine data were selected for the study. The cotinine concentration and ETS exposure rate using urine cotinine was estimated and then compared with the self-reporting measurements. The degree of agreement among measurements of ETS exposure was confirmed. Results: As a result of measuring ETS exposure with urine cotinine, 23,594 (83.8%) out of 28,574 subjects were classified as to exposure groups. This estimate differs significantly from measurements made by self-reporting. In addition, the average concentration of cotinine in non-smokers has decreased to a 10th level over the past 10 years. Based on the biomarker, the sensitivity of the self-reporting was 8.5%-29.0%, the specificity was 16.4%-19.5%, and the kappa value was 2.0%-5.8%. Conclusion: The findings of our study show that self-reporting measurement does not well reflect the extent to which non-smoker's exposure to smoking materials. Whereas cotinine concentration has decreased significantly over the past 10 years, the ETS exposure rate has not reduced. It strongly suggests the need for intervention in the group of non-smokers exposed to low concentrations of smoke. Therefore, an assessment using biomarkers such as cotinine-based measurement should be made in the Health Plan 2030.