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RISS 인기검색어
- 검색키워드
- 저자 : Ren-Chin Wu (검색결과 4 건)
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LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer
Haruko Kunitomi,Yusuke Kobayashi,Ren-Chin Wu,Takashi Takeda,Eiichiro Tominaga,Kouji Banno,Daisuke Aoki 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.2
Objective: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The LAMC1 gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism. Methods: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to identify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting LAMC1 and conducted microarray gene expression assays. Results: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (LZTFL1, TAPT1, SEL1L, PAQR6, NME7, TMEM109, CCDC58, and ANKRD40) that were commonly influenced in HEC50B and SPAC-S by LAMC1 silencing. Conclusion: LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.
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Angel Chao,Yi-Hao Lin,Lan-Yan Yang,Ren-Chin Wu,Wei-Yang Chang,Pi-Yueh Chang,Shih-Cheng Chang,Chiao-Yun Lin,Huei-Jean Huang,Cheng-Tao Lin,Hung-Hsueh Chou,Kuan-Gen Huang,Wen-Ling Kuo,Ting-Chang Chang,Ch 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3
Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. Conclusions: Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.
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An-Shine Chao,Angel Chao,Chyong-Huey Lai,Chiao-Yun Lin,Lan-Yan Yang,Shih-Cheng Chang,Ren-Chin Wu 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.1
Objective: Lynch syndrome (LS) is a hereditar y cancer predisposition syndrome witha significantly increased risk of colorectal and endometrial cancers. Current standardpractice involves universal screening for LS in patients with newly diagnosed colorectal orendometrial cancer using a multi-step screening protocol (MSP). However, MSP may notalways accurately identif y LS cases. To address this limitation, we compared the diagnosticperformance of immediate germline sequencing (IGS) with MSP in a high-risk group. Methods: A total of 31 Taiwanese women with synchronous or metachronous endometrialand colorectal malignancies under went MSP which included immunohistochemical stainingof DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, andgermline sequencing to identif y pathogenic variants. All patients who were excluded duringMSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. Results: Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfullyidentified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutionalMLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly,we obser ved no significant differences in clinical characteristics or overall sur vival betweenpatients with and without LS in our cohort. Conclusion: Our study suggests that IGS may potentially offer a more effective approachcompared to MSP in identif ying LS among high-risk patients. This advantage is evident whenpatients have been pre-selected utilizing specific clinical criteria.
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