Novel combination of serum microRNA for detecting breast cancer in the early stage
Akihiko ShimomuraSho ShiinoJunpei KawauchiSatoko TakizawaHiromi SakamotoJuntaro MatsuzakiMakiko OnoFumitaka TakeshitaShumpei NiidaChikako ShimizuYasuhiro FujiwaraTakayuki KinoshitaKenji TamuraTakahiro Ochiya
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MicroRNA (miRNA), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNA in several large cohorts to identify novel miRNA that can be used to detect early stage breast cancer. We comprehensively evaluated the serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. In addition, 2836 serum samples were obtained from non‐cancer controls, 451 from patients with other types of cancers, and 63 from patients with non‐breast benign diseases. The samples were divided into a training cohort including non‐cancer controls, other cancers and breast cancer, and a test cohort including non‐cancer controls and breast cancer. The training cohort was used to identify a combination of miRNA that could detect breast cancer, and the test cohort was used to validate that combination. miRNA expressions were compared between patients with breast cancer and non‐breast cancer, and a combination of five miRNA (miR‐1246, miR‐1307‐3p, miR‐4634, miR‐6861‐5p and miR‐6875‐5p) was found to be able to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9% and accuracy of 89.7% for breast cancer in the test cohort. In addition, this combination could detect early stage breast cancer (sensitivity of 98.0% for Tis).Limited evidence suggests that inherited predisposing risk variants might affect the disease outcome. In this study, we analyzed the effect of genome-wide association studies—identified breast cancer-risk single nucleotide polymorphisms on survival of early-stage breast cancer patients in a Chinese population. This retrospective study investigated the relationship between 21 GWAS-identified breast cancer-risk single nucleotide polymorphisms and the outcome of 1177 early stage breast cancer patients with a long median follow-up time of 174 months. Cox proportional hazards regression models were used to estimate the hazard ratios and their 95% confidence intervals. Primary endpoints were breast cancer special survival and overall survival while secondary endpoints were invasive disease free survival and distant disease free survival. Multivariate survival analysis showed only the rs2046210 GA genotype significantly decreased the risk of recurrence and death for early stage breast cancer. After grouping breast cancer subtypes, significantly reduced survival was associated with the variant alleles of rs9485372 for luminal A and rs4415084 for triple negative breast cancer. Importantly, all three single-nucleotide polymorphisms, rs889312, rs4951011 and rs9485372 had remarkable effects on survival of luminal B EBC, either individually or synergistically. Furthermore, statistically significant multiplicative interactions were found between rs4415084 and age at diagnosis and between rs3803662 and tumor grade. Our results demonstrate that breast cancer risk susceptibility loci identified by GWAS may influence the outcome of early stage breast cancer patients’ depending on intrinsic tumor subtypes in Chinese women.
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目的．microRNA（miRNA）は約22塩基のnon-coding RNAで標的遺伝子の発現を抑制し，発生·分化の制御など種々の生物学的機能を果たしている．我々は肺癌に於けるmiRNAの異常と，肺癌の発症·進展への関与を検討した．研究計画．癌に関連する可能性が考えられるmiRNA群を選択し，正常肺·肺癌検体におけるmiRNAの発現を比較検討した．また，miRNAやアンチセンスオリゴを細胞内導入し，miRNAの機能を検討した．結果．let-7ファミリーが肺癌で高頻度に発現低下し，その発現低下が予後不良因子であることが判明した．また，miR-17-92クラスターの過剰発現が見出された．このmiR-17-92クラスターの強制発現で増殖促進が見られ，一方，アンチセンスオリゴによる発現抑制が，miR-17-92クラスターを強発現している肺癌細胞株特異的に増殖抑制·細胞死誘導を引き起こした．結論．let-7ファミリーが癌抑制遺伝子として，また，miR-17-92クラスターが癌遺伝子として機能しており，これらmiRNAの異常が，肺癌の発症·進展に深く関与することが示唆された．他のmiRNAの癌への関与も報告され，今後miRNA発現解析の癌の診断·予後予測への応用や，miRNAを用いた治療·miRNAを標的とする治療などの開発が期待される．
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目的将开始由微数组技术在人的胰腺的癌症房间线分析 miRNAs 表示侧面的差别。743 根探针全部的方法 A 根据人，老鼠，和老鼠的已知的 miRNAs 序列被设计。miRNAs 微数组被生产，它的可靠被验证。全部的 RNA 被提取， miRNAs 与胰腺的癌症房间衬里的人(SW1990， Capan-2， BxPC-3， Aspc-1，和 Panc1 ) 和不朽的人被分开胰腺的管上皮的房间线 H6C7。他们用 T4 RNA ligase 被标记，当时是有微数组的 hybridized。通过数组扫描和分析，在胰腺的癌症的 miRNAs 表达式侧面被获得。结果被北弄污和 RT-PCR 验证。与胰腺的癌症有关的 63 miRNAs 全部的结果 A 被发现是在 5 根胰腺的癌症房间线表示的差别，包括 25 下面调整并且 38 起来调整的 miRNAs。mir-21 和 let-7 的表情也被证实。结果建议了侧面能在胰腺的癌症房间被发现的那 miRNAs 表情的结论。
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Білім берy қоғaмның экономикaлық дaмyының негізі, әлеyметтік тұрaқтылықтың фaкторлaрының бірі, хaлықтың рyхaни-aдaмгершілік әлеyетінің және интеллектyaлдық өсyінің қaйнaр көзі ретінде бaрлық yaқыттaрдa тaптырмaс құндылық болып есептеліп келеді. Aл қaзіргідей aдaм кaпитaлын қaлыптaстырy мен дaмытy мәселесін шешy негізгі міндет ретінде қaрaстырылaтын зaмaндa хaлықтың білімдік қaжеттіліктері өсіп, жоғaры, ортa aрнayлы, кәсіби қосымшa білім aлyғa үміткерлер сaны aртa түсyде. Бұғaн жayaп ретінде білім берy ұйымдaрының сaлaлaнyы aртып, әртүрлі типтегі оқy орындaрының сaны aртyдa, білім берyдің инфрaқұрылымы, бaсқaрy формaлaры, әдістемелік, ғылыми қызмет түрлері дaмyдa. Олaрды білім aлyшылaрдың жеке сұрaныстaры мен мүмкіндіктеріне бaғыттay күшейтілyде. Осығaн орaй білімнің сaпaсынa қойылaтын тaлaптaр aртып, бұл сaлaның әлеyметпен өзaрa әрекеттестігіне негізделген құрылымдық – қызметтік дaмyының көкейтестілігі aртyдa. Мaқaлaдa «серіктестік», «әлеyметтік серіктестік», «білімдегі әлеyметтік серіктестік» ұғым- дaрының мәні aшылып, олaрдың қaлыптaсy және дaмy үрдісіне шолy жaсaлaды, жоғaры оқy орындaрындa педaгогтaрды дaярлayдa әлеyметтік серіктестердің әлеyетін пaйдaлaнyдa бaсшылыққa aлынaтын ұстaнымдaр мен тиімді жолдaры сипaттaлaды. Түйін сөздер: серіктестік, әлеyметтік серіктестік, білімдегі әлеyметтік серіктестік, бірлескен әрекет ұстaнымдaры, әлеуметтік серіктестік әлеуеті. Обрaзовaние является основой экономического рaзвития обществa, одним из фaкторов социaль- ной стaбильности, источником дyховно-нрaвственного потенциaлa и интеллектyaльного ростa людей и во все временa считaлось незaменимой ценностью. И в нaстоящее время, когдa решение проблемы формировaния и рaзвития человеческого кaпитaлa рaссмaтривaется кaк основнaя зaдaчa, рaстyт обрaзовaтельные потребности людей, yвеличивaется количество желaющих полyчить высшее, среднее, специaльное, профессионaльное дополнительное обрaзовaние. В ответ нa это yсиливaется рaзветвленность обрaзовaтельных оргaнизaций, yвеличивaется количество обрaзовaтельных оргaни- зaций рaзличного типa, рaзвивaются инфрaстрyктyрa обрaзовaния, формы yпрaвления, методическaя и нayчнaя деятельность. Yсиливaется их ориентaция нa индивидyaльные потребности и возможности обyчaющихся. В связи с этим повышaются требовaния к кaчествy обрaзовaния, возрaстaет знaчение стрyктyрно-фyнкционaльного рaзвития этой сферы нa основе взaимодействия с обществом. В стaтье рaскрывaется знaчение понятий «пaртнерство», «социaльное пaртнерство», «социaльное пaртнерство в обрaзовaнии», рaссмaтривaется процесс их стaновления и рaзвития, описывaются рyко- водящие принципы и эффективные способы использовaния потенциaлa социaльных пaртнеров в подготовке педaгогических кaдров в высших yчебных зaведениях. Ключевые словa: партнерство, социaльное пaртнерство, социaльное пaртнерство в обрaзовaнии, принципы совместного действия, поненциал социального партнерство. Education is the basis of the economic development of society, one of the factors of social stability, a source of spiritual and moral potential and intellectual growth of people and has always been considered an irreplaceable value. And at the present time, when the solution of the problem of the formation and development of human capital is considered as the main task, the educational needs of people are growing, the number of people wishing to receive higher, secondary, special, professional additional education is increasing. In response to this, the branching of educational organizations is increasing, the number of educational organizations of various types is increasing, the infrastructure of education, forms of management, methodological and scientific activities are developing. Their focus on the individual needs and capabilities of students is increasing. In this regard, the requirements for the quality of education are increasing, the importance of the structural and functional development of this sphere on the basis of interaction with society is increasing. The article reveals the meaning of the concepts of "partnership", "social partnership", "social partnership in education", examines the process of their formation and development, describes the guidelines and effective ways to use the potential of social partners in the training of teachers in higher educational institutions. Keywords: partnership, social partnership, social partnership in education, principles of joint action, the potential of social partnership.
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地方性甲状腺腫は臨床, 病理学的に複雑な経過を示し, 疫学的, 病理学的発生論や治療の選択に多くの難題が残されている. 著者は本症の病期検討および妥当な病期分類がこれらの検索, 解明にきわめて有用であると着目し, 甲状腺剔出を行なった地方性甲状腺腫336例を臨床, 病理学的に精査し下記の結果をえた. 1) 地方性甲状腺腫は臨床的, 病理学的経過からStage 1;過形成期, Stage 2;腫大期, Stage 3;結節形成期と分類できた. 2) 本症は病期の進行に伴い病悩期間は長くなり, 甲状腺腫は増大し種々の局所圧迫症状をみるが, 合併症がなければ全身的, 臨床生化学的所見はほぼ正常である. 3) 臨床, 病理学的に本症はStage 1からStage 2さらにStage 3に進行し, Stage 3は終末期である. 4) 病変の占居部位はStage 1では両葉性, Stage 2では両葉性と単葉性がほぼ等しく, Stage 3では単葉性が多い点からもStageの進行度を裏付けられる. 5) 336例のうち男性39例, 女性297例, 男女比1:7.6で, 発生のピークは女性では20才から30才代, 男性は30才から40才代であった. 6) 手術適応例は若年者より成人に多く, 女性は男性より著しく多い. ヨード治療の効果が若年者ほど良好で, 男性は女性よりもヨード感受性が高いためである. 7) Stage 3の9.4%に甲状腺機能亢進症 (4.03%), 腺腫 (1.34%), 甲状腺癌 (4.03%) などの共存疾患がみられた. 8) ヨード治療はStage 1では効果的であるがStage 2では無効でStage 3に進行し, 種々の合併症を起こすこともあり, Stage 2における手術が望ましい.
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MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.
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Purpose of the study . Determination of the expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 in colon tumor tissue depending on the clinical and morphological features of the tumor and the effectiveness of treatment. Materials and methods . The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years with the average age of 54 years. Taking into account the local prevalence of the process patients received surgical or combined treatment, including neoadjuvant chemotherapy, in the clinics of the Cancer Research Institute, Tomsk NRMC. MicroRNA expression was determined by polymerase chain reaction (PCR) in real time. Results . The obtained information revealed the relation of microRNA‑130 to the tumor size. The development of regional metastases was associated with changes in microRNA‑130, microRNA‑194 and microRNA‑605. The level of histological organization of the tumor was associated with microRNA‑34, microRNA‑130, microRNA‑148, and the response to therapy – with microRNA‑130, microRNA‑148 and microRNA‑605. In addition, according to the study, the significance of microRNA‑130 was revealed, which is associated with tumor spread, histological differentiation and response to antitumor therapy. Conclusion . The features of expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 associated with clinical and morphological features of colon tumors were revealed. Correlations between the studied indicators are noted, which probably determine the outcome and prognosis of the disease.
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Abstract Breast cancer is a frequent female malignant tumor with high mortality and poor prognosis. Peroxidasin like (PXDNL) has many biological functions, including characteristic activity of hormone biosynthesis, host defense, and cell motility. In addition, PXDNL is closely connected with the progression of breast cancer. In this study, we found that PXDNL may be an independent prognostic biomarker of breast cancer. We tested the mRNA expression of PXDNL in breast cancer by detecting The Cancer Genome Atlas (TCGA) database. The chi-squared test was used to evaluate clinical correlation. The receiver operating characteristic (ROC) curves were drawn to evaluate diagnosis potential in breast cancer. Subsequently, survival analyses were performed to identify the relevance between the expression of PXDNL and the overall survival/relapse-free survival of patients with breast cancer. Univariate/multivariate Cox regression model was executed to detect risk factors affecting the prognosis of patients with breast cancer. PXDNL is highly expressed in breast cancer tissues and is related to survival status of patients. The ROC curve showed that PXDNL had beneficial diagnostic ability in breast cancer. Survival analysis indicated that patients with breast cancer with high PXDNL expression generally had decreased overall survival/relapse-free survival. Univariate/multivariate Cox model analyses further suggested an association between PXDNL expression and prognosis of patients with breast cancer. High PXDNL expression is a potential and independent prognostic biomarker in breast cancer.
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