• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3197-3203
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• 2013

Background: microRNAs (miRNAs) that regulate proliferation, invasion and metastasis are considered to be the principal molecular basis of tumor heterogeneity. Breast cancer is not a homogeneous tissue. Thus, it is very important to perform microarray-based miRNA screening of tumors at different sites. Methods: Breast tissue samples from the centers and edges of tumors of 30 patients were classified into 5 clinicopathological subtypes. In each group, 6 specimens were examined by microRNA array. All differential miRNAs were analyzed between the edges and centers of the tumors. Results: Seventeen kinds of miRNAs were heterogeneously distributed in the tumors from different clinicopathological subtypes that included 1 kind of miRNA in Luminal A and Luminal B Her2+ subtypes, 4 kinds in Luminal A and Her2 overexpression subtypes, 6 kinds in Luminal B Ki67+ and Luminal B Her2+ subtypes, 2 kinds between Luminal B Ki67+ and triple-negative breast cancer (TNBC) subtypes, 2 kinds between Luminal B Her2+ and TNBC subtypes, and 2 kinds between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Twenty kinds of miRNAs were homogenously distributed in the tumors from different clinicopathological subtypes that included 6 kinds of miRNAs in Luminal B Ki67+ and Luminal B Her2+ subtypes, 1 kind in Luminal B Ki67+ and Her2 overexpression subtypes, 10 kinds between Luminal B Ki67+ and TNBC subtypes, 2 kinds in Luminal B Her2+ and TNBC subtypes, and 1 kind between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Conclusions: A total of 37 miRNAs were significantly distributed in tumors from the centers to edges, and in all clinicopathological subtypes.

• Korean Journal of Radiology
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• 제22권7호
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• pp.1021-1033
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• 2021

Objective: To assess the expression of vascular normalization genes in different molecular subtypes of breast cancer and to determine whether molecular subtypes with a higher vascular normalization gene expression can be identified using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI). Materials and Methods: This prospective study evaluated 306 female (mean age ± standard deviation, 50 ± 10 years), recruited between January 2014 and August 2017, who had de novo breast cancer larger than 1 cm in diameter (308 tumors). DCE MRI followed by IVIM DWI studies using 11 different b-values (0 to 1200 s/mm²) were performed on a 1.5T MRI system. The Tofts model and segmented biexponential IVIM analysis were used. For each tumor, the molecular subtype (according to six [I-VI] subtypes and PAM50 subtypes), expression profile of genes for vascular normalization, pericytes, and normal vascular signatures were determined using freshly frozen tissue. Statistical associations between imaging parameters and molecular subtypes were examined using logistic regression or linear regression with a significance level of p = 0.05. Results: Breast cancer subtypes III and VI and PAM50 subtypes luminal A and normal-like exhibited a higher expression of genes for vascular normalization, pericyte markers, and normal vessel function signature (p < 0.001 for all) compared to other subtypes. Subtypes III and VI and PAM50 subtypes luminal A and normal-like, versus the remaining subtypes, showed significant associations with K^trans, k_ep, v_p, and IAUGC_BN90 on DEC MRI, with relatively smaller values in the former. The subtype grouping was significantly associated with D, with relatively less restricted diffusion in subtypes III and VI and PAM50 subtypes luminal A and normal-like. Conclusion: DCE MRI and IVIM parameters may identify molecular subtypes of breast cancers with a different vascular normalization gene expression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4113-4117
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• 2012

Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the $ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with $ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients. $ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between $ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that $ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6109-6113
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• 2014

Background: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. Aim: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. Materials and Methods: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. Results: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal-like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. Conclusions: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype.

• 한국동물학회지
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• 제31권2호
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• pp.133-141
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• 1988

본 연구는 polyacryiamide gel등을 전기영동을 응용, 보존시간에 따른 정액반, 질액반 등에서 PGM$_1$아형의 검출 및 효소활성의 안전성을 조사하여 다음과 같은 결론을 얻었다. (1). 정액반의경우, 실온에서 보존후 7일에는 85%,14일에는 15%의 PGM$_1$아형의 판정이 가능하였고, 21일에는 전혀 판정이 불가능 하였다. (2). 질액반의 경우, 실온에서 보존 후 7일에는 675의 PGM$_1$아형의 판정이 가능하였으나, 14일에는 전혀 불가능 하였다. 한편, 질액에 정액이 혼합된 경우, 질액의 PGM$_1$아형을 판정함으로서, 정액의 PGM$_1$아형의 추정이 가능하였다. 이 결과를 통하여 실제 법생물학 분야에 활용이 가능하다고 인정하였다.

• Communications for Statistical Applications and Methods
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• 제26권4호
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• pp.411-430
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• 2019

Tumor development is driven by complex combinations of biological elements. Recent advances suggest that molecularly distinct subtypes of breast cancers may respond differently to pathway-targeted therapies. Thus, it is important to dissect pathway disturbances by integrating multiple molecular profiles, such as genetic, genomic and epigenomic data. However, missing data are often present in the -omic profiles of interest. Motivated by genomic data integration and imputation, we present a new statistical framework for pathway significance analysis. Specifically, we develop a new strategy for imputation of missing data in large-scale genomic studies, which adapts low-rank, structured matrix completion. Our iterative strategy enables us to impute missing data in complex configurations across multiple data platforms. In turn, we perform large-scale pathway analysis integrating gene expression, copy number, and methylation data. The advantages of the proposed statistical framework are demonstrated through simulations and real applications to breast cancer subtypes. We demonstrate superior power to identify pathway disturbances, compared with other imputation strategies. We also identify differential pathway activity across different breast tumor subtypes.

• 말소리와 음성과학
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• 제2권2호
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• pp.93-100
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• 2010

The purpose of this study was to investigate the differences of feeding ability and articulatory function in the children with spastic cerebral palsy and typically developing children according to feeding subtypes. The feeding subtypes were limited by chewing, cup drinking and spoon feeding. 14 children with spastic cerebral palsy and 14 typically developing children were participated in this study. The results were following as; First, there were significant differences in overall articulatory function between two groups Second, all scores of articulators' function according to feeding subtypes in children with cerebral palsy was significantly higher than typically developing children Third, chewing mode in feeding subtypes was highly correlated with lip and tongue movement. compared to another Finally, the correlation between spoon feeding and mobility of lip and tongue was high in both groups. These results suggested that These results suggest that the effort to find out the differences feeding ability and appliances for articulatory function in CP children are meaningful in catching their speech ability indirectly. Moreover, the more organized feeding skills should be discussed in the relationship with verbal and nonverbal development.

• Journal of Microbiology and Biotechnology
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• 제20권1호
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• pp.63-70
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• 2010

Novel influenza A (H1N1) is a newly emerged flu virus that was first detected in April 2009. Unlike the avian influenza (H5N1), this virus has been known to be able to spread from human to human directly. Although it is uncertain how severe this novel H1N1 virus will be in terms of human illness, the illness may be more widespread because most people will not have immunity to it. In this study, we compared the codon usage bias between the novel H1N1 influenza A viruses and other viruses such as H1N1 and H5N1 subtypes to investigate the genomic patterns of novel influenza A (H1N1). Totally, 1,675 nucleotide sequences of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A virus, including H1N1 and H5N1 subtypes occurring from 2004 to 2009, were used. As a result, we found that the novel H1N1 influenza A viruses showed the most close correlations with the swine-origin H1N1 subtypes than other H1N1 viruses, in the result from not only the analysis of nucleotide compositions, but also the phylogenetic analysis. Although the genetic sequences of novel H1N1 subtypes were not exactly the same as the other H1N1 subtypes, the HA and NA genes of novel H1N1s showed very similar codon usage patterns with other H1N1 subtypes, especially with the swine-origin H1N1 influenza A viruses. Our findings strongly suggested that those novel H1N1 viruses seemed to be originated from the swine-host H1N1 viruses in terms of the codon usage patterns.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7819-7824
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• 2015

Purpose: To subtype breast cancer (BC) in Saudi women according to the recent molecular classification and to correlate these subtypes with available clinicopathological parameters. Materials and Methods: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (Her2/neu) immunostaining was semi-quantitatively assessed to define molecular subtypes of luminal A and B, HER-2 and triple negative (basal-like) in BC paraffin embedded sections from 115 Saudi female patients diagnosed between 2005 to 2015 at the Department of Pathology, King Fahd Hospital, Almadinah, Saudi Arabia. Results: The most common subtypes were luminal A (47%), followed by luminal B (27.8%) and basal like subtypes (18.3%), whereas HER-2 was the least common subtype (6.9%). Luminal A was predominantly found in the old age group, with low tumor grade (p<0.001) and small tumor size, whereas HER-2 and basal-like subtypes were significantly associated with young age, high tumor grade, lymph node metastasis and lymphovascular invasion (p<0.03, 0.004, 0.05 and 0.04 respectively). All subtypes showed advanced clinical stage at the time of presentation. Conclusions: Molecular subtypes of Saudi BC patients in Almadinah region are consistent with most of the worldwide subtyping. The biological behaviour of each molecular subtype could be expected based on its characteristic clinicopathological features. Along with other prognostic indicators, molecular subtyping would be helpful in predicting prognosis and management of our BC patients. We recommend screening and early diagnosis of BC in our population.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5811-5816
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• 2013

Background: Breast cancer is the most common cancer among women. Molecular subtypes are important in determining prognosis. This study evaluated five-year disease-free survival among four molecular subtypes in patients with early stages of breast cancer. Materials and Methods: In this retrospective descriptive-analytical study, information on patients with breast cancer between 2001-2010 was evaluated. Five hundred ninety two patients in the early stages of breast cancer (stages 1 and 2) were selected to undergo anthracycline-based chemotherapy. Relapse, death or absence (censor) were considered as the end of the study. Patients based on ER, PR and HER-2 expression were divided into four subtypes (luminal A, luminal B, HER-2 enriched and triple negative). Information based upon questionnaire was analysed. To show the patients survival rate, life table and Kaplan-Meyer methods were used, and for comparing mean survival among different groups, the Log-Rank test was utilized. Results: Mean age at diagnosis was $47.9{\pm}9.6$. Out of the 592 patients, 586 were female (99%) and 6 were male (1%). Considering breast cancer molecular subtypes, 361 patients were in the luminal A group (61%), 49 patients in the luminal B group (8.3%), 48 patients in the HER-2 enriched group (8.1%) and 134 in the triple negative group (22.6%). Mean disease-free survival was 53.7 months overall, 55.4 months for the luminal A group, 48.3 months for the luminal B group, 43 months for the HER-2enriched group and 54.6 months for the triple negatives. Disease free survival differed significantly among the molecular subtypes (p value=0.0001). Conclusions: The best disease-free survival rate was among the luminal A subgroup and the worst disease-free survival rate was among the HER-2 enriched subgroup. Disease free survival rate in the HER-2 positive groups (luminal B and HER-2 enriched) was worse than the HER-2 negative groups (luminal A and triple negative).