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An Integrated Approach For Uncovering Novel DNA Methylation Biomarkers For Non-small Cell Lung Carcinoma

為了解決adi af-16擴頻的問題，作者VAIBHAV KUMAR SUNKARIA 這樣論述：

Introduction - Lung cancer is one of primal and ubiquitous cause of cancer related fatalities in the world. Leading cause of these fatalities is non-small cell lung cancer (NSCLC) with a proportion of 85%. The major subtypes of NSCLC are Lung Adenocarcinoma (LUAD) and Lung Small Cell Carcinoma (LUS

C). Early-stage surgical detection and removal of tumor offers a favorable prognosis and better survival rates. However, a major portion of 75% subjects have stage III/IV at the time of diagnosis and despite advanced major developments in oncology survival rates remain poor. Carcinogens produce wide

spread DNA methylation changes within cells. These changes are characterized by globally hyper or hypo methylated regions around CpG islands, many of these changes occur early in tumorigenesis and are highly prevalent across a tumor type.Structure - This research work took advantage of publicly avai

lable methylation profiling resources and relevant comorbidities for lung cancer patients extracted from meta-analysis of scientific review and journal available at PubMed and CNKI search which were combined systematically to explore effective DNA methylation markers for NSCLC. We also tried to iden

tify common CpG loci between Caucasian, Black and Asian racial groups for identifying ubiquitous candidate genes thoroughly. Statistical analysis and GO ontology were also conducted to explore associated novel biomarkers. These novel findings could facilitate design of accurate diagnostic panel for

practical clinical relevance.Methodology - DNA methylation profiles were extracted from TCGA for 418 LUAD and 370 LUSC tissue samples from patients compared with 32 and 42 non-malignant ones respectively. Standard pipeline was conducted to discover significant differentially methylated sites as prim

ary biomarkers. Secondary biomarkers were extracted by incorporating genes associated with comorbidities from meta-analysis of research articles. Concordant candidates were utilized for NSCLC relevant biomarker candidates. Gene ontology annotations were used to calculate gene-pair distance matrix fo

r all candidate biomarkers. Clustering algorithms were utilized to categorize candidate genes into different functional groups using the gene distance matrix. There were 35 CpG loci identified by comparing TCGA training cohort with GEO testing cohort from these functional groups, and 4 gene-based pa

nel was devised after finding highly discriminatory diagnostic panel through combinatorial validation of each functional cluster.Results – To evaluate the gene panel for NSCLC, the methylation levels of SCT(Secritin), FOXD3(Forkhead Box D3), TRIM58(Tripartite Motif Containing 58) and TAC1(Tachikinin

1) were tested. Individually each gene showed significant methylation difference between LUAD and LUSC training cohort. Combined 4-gene panel AUC, sensitivity/specificity were evaluated with 0.9596, 90.43%/100% in LUAD; 0.949, 86.95%/98.21% in LUSC TCGA training cohort; 0.94, 85.92%/97.37 in GEO 66

836; 0.91,89.17%/100% in GEO 83842 smokers; 0.948, 91.67%/100% in GEO83842 non-smokers independent testing cohort. Our study validates SCT, FOXD3, TRIM58 and TAC1 based gene panel has great potential in early recognition of NSCLC undetermined lung nodules. The findings can yield universally accurate

and robust markers facilitating early diagnosis and rapid severity examination.

不在彼方－從親密關係探討隔代教養經驗

為了解決adi af-16擴頻的問題，作者李佳芸 這樣論述：

研究者以自身為引線，將親密關係中所經驗到的內在需求、衝突與防衛作為入口，進而回望過往受隔代教養的生命經驗，透過自我敘說的方式，在之中內觀自我，最後將自己與外祖父母、父母及親密關係進行縫補，進而真正分離，擁有自己。研究者從過往親密關係的斷裂，省思自我遭困的囹圄，跟著線索回到早年經驗翻找答案。從與祖父母的隔代教養經驗中，看見自己被以愛為名所受的困身，重新檢視自己在孫女與女兒位子間矛盾的擺盪；從回到父母身邊的生長經歷，正視那些被丟棄的怒氣，讓自己回到女兒的角色；從與伴侶的親密關係中，學習交託眼淚，卸下武裝，誠實表達需求。在敘說歷程中，從難以和家分離，到邁向個體化的成長。