<i>DYSF</i> expression in clear cell renal cell carcinoma: A retrospective study of 2 independent cohorts

Ha, Mihyang,Jeong, Hoim,Roh, Jong Seong,Lee, Beomgu,Han, Myoung-Eun,Oh, Sae-Ock,Sohn, Dong Hyun,Kim, Yun Hak Elsevier 2019 Urologic oncology Vol.37 No.10

<P><B>Abstract</B></P> <P><B>Objective</B></P> <P>Renal cell carcinoma (RCC) is the most typical type of kidney cancer in adults. Hypercalcemia is a well known paraneoplastic syndrome associated with RCC and recent studies have reported that hypercalcemia is closely related to the poor prognosis of RCC patients. Clear cell RCC (ccRCC) is the most common and aggressive subtype of RCC. Although the histological classification of RCC is important for determination of appropriate treatment strategies, effective biomarkers for predicting prognosis of ccRCC have not yet been identified. Since calcium levels affect the prognosis of RCC patients, we evaluated whether the calcium-sensing genes on the plasma membrane, including those encoding calcium channels, CaSR, GPRC6a, and <I>DYSF</I>, could be used as biomarkers to predict the prognosis of ccRCC patients.</P> <P><B>Methods</B></P> <P>Information from 537 patients from The Cancer Genome Atlas (TCGA; <I>n</I> = 446) and International Cancer Genome Consortium (ICGC; <I>n</I> = 91) was used in this study. Among these genes, <I>DYSF</I> was the only gene whose expression correlated with overall survival of both TGCA and ICGC patients.</P> <P><B>Results</B></P> <P>Although <I>DYSF</I> gene expression was higher in ccRCC tissue than in normal kidney tissue, Kaplan-Meier curves showed that the survival rate of ccRCC patients with high <I>DYSF</I> expression was significantly higher than that of patients with low <I>DYSF</I> expression (TCGA, <I>P</I> < 0.0001; ICGC, <I>P</I> = 0.0011). We also validated the potential of <I>DYSF</I> as a prognostic biomarker for ccRCC by conducting a time-dependent area under the curve (AUC) analysis and 5-years receiver operating characteristic curve analysis. Finally, multivariate regression analysis revealed that the expression of <I>DYSF</I> is independent of other prognostic parameters (TCGA, <I>P</I> = 0.017; ICGC, <I>P</I> = 0.006).</P> <P><B>Conclusions</B></P> <P>These results suggested that <I>DYSF</I> may play a suppressive role in the progression of ccRCC and could act as a promising prognostic biomarker for predicting the survival of ccRCC patients.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Higher expression of <I>DYSF</I> is associated with better prognosis of ccRCC patients. </LI> <LI> <I>DYSF</I> expression in tumor tissue is higher than that in normal tissue. </LI> <LI> <I>DYSF</I> gene might be a potential prognostic biomarker for ccRCC patients. </LI> </UL> </P>

<b><i>TMEM18</i></b>: A Novel Prognostic Marker in Acute Myeloid Leukemia

Ha, Mihyang,Kim, Ji-Young,Han, Myoung-Eun,Kim, Ga Hyun,Park, Si Young,Jeong, Dae Cheon,Oh, Sae-Ock,Kim, Yun Hak S.Karger 2018 Acta haematologica Vol.140 No.2

<P><B><I>Background:</I></B> Certain nuclear envelope proteins are associated with important cancer cell characteristics, including migration and proliferation. Abnormal expression of and genetic changes in nuclear envelope proteins have been reported in acute myeloid leukemia (AML) patients. Transmembrane protein 18 <I>(TMEM18)</I>, a nuclear envelope protein, is involved in neural stem cell migration and tumorigenicity. <B><I>Methods:</I></B> To examine the prognostic significance of <I>TMEM18</I> in AML patients, we analyzed an AML cohort from The Cancer Genome Atlas (TCGA, <I>n</I> = 142). <B><I>Results:</I></B> Kaplan-Meier survival analysis revealed that <I>TMEM18</I> overexpression was associated with a better AML prognosis with good discrimination (<I>p</I> = 0.019). Interestingly, this ability to predict the prognosis was significant in male AML patients, but not in female ones. C-index and area-under-the-curve analyses further supported this discriminative ability and multivariate analysis confirmed its prognostic significance (<I>p</I> = 0.00347). Correlation analysis revealed that <I>TMEM18</I> had a statistically significant positive correlation with nuclear envelop protein 133 <I>(NUP133)</I>, <I>NUP35</I>, <I>NUP54</I>, <I>NUP62</I>, and <I>NUP88</I>. <B><I>Conclusion:</I></B> Because the current AML prognostic factors do not take mRNA expression into consideration unlike other cancers, the development of mRNA-based prognostic factors would be beneficial for accurate prediction of the survival of AML patients. Therefore, <I>TMEM18</I> gene is a potential biomarker for AML.</P>

[P10-154] Effect of Capsosiphon fulvecense Extract on the Charge of Serum Lipid level and Platelet Aggregation in Ovariectomized Rat

Mihyang Kim,Kyung-Ha Choi,Mi-Hwa Park 한국식품영양과학회 2005 한국식품영양과학회 학술대회발표집 Vol.2005 No.10

Effects of three mulberry cultivars Extracts in Ovariectomized Rats

Kyung-Ha Choi,Jeung-Yub Kim,Mi-Wha Park,Mihyang Kim 한국생명과학회 2005 한국생명과학회 심포지움 Vol.44 No.-

The Effect of Mulberry Ethanol Extracts on Collagen Synthesis in Ovariectomized Rats

Kyung-Ha Choi,Mi-hwa Park,Mihyang Kim 한국생명과학회 2005 한국생명과학회 심포지움 Vol.45 No.-

[P8-112] Improvement haemostasis mediated effects of Garlic extract on Hepatotoxidity in Carbon Tetrachloride一intoxicated Rats

Young-Ae Lee,Kyung-Ha Choi,Gun-Ho Bae,Mihyang Kim,Sung-Rim Kang 한국식품영양과학회 2007 한국식품영양과학회 학술대회발표집 Vol.2007 No.10

Evaluation of the prognostic significances of γ-secretase genes in pancreatic cancer

Jeon, Yun Ho,Ha, Mihyang,Kim, Sung Won,Kim, Mun Ju,Lee, Chi-Seung,Oh, Chang-Kyu,Han, Myoung-Eun,Oh, Sae-Ock,Kim, Yun Hak D.A. Spandidos 2019 Oncology letters Vol.17 No.5

<P>With the growing requirement for novel prognostic biomarkers for pancreatic cancer, many studies have focused on clinical and/or genomic variables. Although many studies have been performed, carbohydrate antigen 19-9 is the only biomarker in clinical use. Therefore, the present study examined whether γ-secretase genes, including presenilin (<I>PSEN</I>), nicastrin (<I>NCSTN</I>), presenilin enhancer protein 2 (<I>PSENEN</I>), and anterior pharynx-defective 1 (<I>APH1</I>-), could serve as prognostic factors for pancreatic cancer. The cohorts selected included >100 pancreatic cancer patients. Patient data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE21501). The prognostic roles of the γ-secretase genes were analyzed by several survival analysis methods. Among the γ-secretase genes, the prognosis tended to be worse in the 2 cohorts with increasing expression of <I>PSEN1, APH1A</I>, and <I>PSENEN</I>, while the remaining genes were the opposite in the 2 cohorts. Notably, although the patient characteristics were quite different, <I>APH1A</I> was statistically significantly associated with prognosis in the 2 cohorts. The hazard ratio of <I>APH1A</I> for overall survival was 1.598 (TCGA) and 2.724 (GSE21501). These results contribute to the study of γ-secretase in pancreatic cancer. We believe that γ-secretase, particularly <I>APH1A</I>, will be a new prognostic biomarker for pancreatic cancer.</P>

ALKBH5 gene is a novel biomarker that predicts the prognosis of pancreatic cancer

Sung Hwan Cho,Mihyang Ha,Yong Hoon Cho,Je Ho Ryu,Kwangho Yang,Kang Ho Lee,Myoung-Eun Han,Sae-Ock Oh,Yun Hak Kim 한국간담췌외과학회 2018 Annals of hepato-biliary-pancreatic surgery Vol.22 No.4

Backgrounds/Aims: Discovery of new prognostic factors for cases in which the pancreatic cancer scoring and staging system does not result in a clear definition is imperative. We examined the role of Human AlkB homolog H5 (ALKBH5) as a prognostic marker for pancreatic cancer. Methods: Patient data were extracted from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). The prognostic value of ALKBH5 was confirmed via analysis of ALKBH5 and other clinical factors, such as age, sex, and stage, using the time-dependent area under the curve (AUC) of Unos C-index, the AUC value of the receiver operating characteristics (ROC) at three years, the Kaplan-Meier survival curve, and multivariate analysis. Results: ALKBH5 showed excellent prognosis prediction in comparison with existing markers in the two independent cohorts (n=262). Kaplan-Meier survival analysis showed that ALKBH5 expression was positively associated with overall survival (log-rank test, ICGC, p=0.001; TCGA, p=0.01). Notably, comparison of C-index and AUC values in ROC analysis showed that ALKBH5 was associated with high C-index and AUC values compared with other clinical variables (C-index: ICGC, 0.621; TCGA, 0.614 and AUC at three years: ICGC, 0.609; TCGA, 0.558). Multivariate analysis demonstrated that ALKBH5 is an independent prognostic factor (ICGC, p=0.0123; TCGA, p<0.001). Conclusions: These findings contribute to the study of RNA methylation in pancreatic cancer. We believe that ALKBH5 is a new prognostic marker for pancreatic cancer.

The effect of high concentration of L-ascorbic acid on the growth of chondrocytes cell

Jeang-Yub Kim,Kyung-Ha Choi,Mihyang Kim 한국생명과학회 2004 한국생명과학회 심포지움 Vol.41 No.-

오디가 난소를 절제한 흰쥐 결함조직 중의 collagen 함량 변화에 미치는 영향

최경하,박미화,김미향,Choi Kyung-Ha,Park Mi-Hwa,Kim Mihyang 한국생명과학회 2005 생명과학회지 Vol.15 No.6

폐경을 앞둔 여성에게는 폐경을 전후하여 지속되는 골 손실 가속화 등의 문제점을 가지고 있다. 그러므로 본 연구에서는 인위적 폐경을 유발시킬 수 있는 난소 절제 쥐에서의 골 손실의 유무를 결합조직 중의 collagen함량 변화를 통하여 그 효과를 검토하였다. 그 결과 생화학적 골 대사 지표인 혈 중 ALP활성은 난소 절제로(OVX-control)로 인하여 증가하는 반면, 난소 절제 후 오디 추출물 투여(OVX-EE, OVX-EA)로 혈 중 ALP활성은 감소하는 경향을 보여 골 흡수를 저하시킬 수 있는 가능성을 나타내었다. 한편 난소 절제 후 오디 추출물 투여에 의해 폐 조직과 골 $\cdot$ 연골 조직에서 collagen 함량이 증가하는 경향을 보였고, 그 중 연골 조직에서는 collagen 함량의 저하가 정상적으로 회복되었다. 한편 피부 조직에서도 난소 절제 후 오디 추출물 투여군 모두에서 collagen 합성량이 유의적으로 증가하였다. 오디 추출물이 estrogen감소로 인한 collagen 합성저하를 회복시킨 본 실험 결과로 미루어 보아 오디 중의 phytoestrogen이 estrogen유사효과를 나타냄을 알 수 있었고, 국내산 오디뿐만 아니라 중국산 오디에서도 갱년기 유도에 의한 collagen 함량 저하를 회복하는 결과가 나타났으므로 외인성 estrogen 투여로 인한 부작용을 줄여 줄 수 있을 것으로 기대된다. 이상과 같이 폐경기 여성에게 오디의 섭취는 폐경으로 인한 장애를 감소시키기 위하여 estrogen의 장기간 복용에 의한 부작용을 오디중의 phytoestrogen이 estrogen대체 작용을 함으로써 그 부작용을 감소시켜 줄 것으로 사료되며, 이들의 구조 및 기전에 대해서는 앞으로 연구가 더 필요한 것으로 생각된다. The aim of this study was to evaluate effects of mulberry cultivars extracts on the collagen content of the connective tissues in ovariectomized rats. From day 2 until day 37 after ovariectomy, Sprague-Dawley female rats were randomly assigned to the following groups : sham-operated rats (Sham), ovariectomized control rats (OVX-control), and ovariectomized rats supplemented with $80\%$ ethyl alcohol extracts from various kinds of Tajikistan mulberry, Korea mulberry and China mulberry at 200 mg/kg bw/day, respectively. The mulberry extracts were orally administrated at 1 mL per day. The OVX rats were significantly heavier than the sham-operated rats were at all time points, but supplementation with the mulberry extracts tended to gain weight less than OVX-control did. The ovariectomy caused a decreasing in the levels of collagen content in bone and cartilage tissues. However, supplementation with mulberry extracts prevented the decrease in the collagen level in bone and cartilage tissues. Therefore, it may be used to possibly improve the quality of life in menopausal women.