Cancer Genomics & Proteomics最新文献

{"title":"Comparative Proteomics of ccRCC Cell Lines to Identify Kidney Cancer Progression Factors.","authors":"Juhee Park, Hyunchae Sim, Eun Hye Lee, Bum Soo Kim, Jae-Wook Chung, Yun-Sok Ha, Tae Gyun Kwon, Sangkyu Lee, Jun Nyung Lee","doi":"10.21873/cgp.20480","DOIUrl":"10.21873/cgp.20480","url":null,"abstract":"<p><strong>Background/aim: </strong>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, accounting for approximately 75% of kidney cancers. The objective of this study was to identify novel progression markers for ccRCC based on proteomics, with the goal of stage determination and early diagnosis of kidney cancer patients.</p><p><strong>Materials and methods: </strong>We performed quantitative global proteomics coupled with Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and high-resolution tandem mass spectrometry on kidney-derived cells, including HEK-293, 786-O (primary ccRCC), and Caki-1 (metastatic ccRCC) cells, to investigate the novel progression factors of ccRCC.</p><p><strong>Results: </strong>In this study, a total of 1,106 proteins were quantified. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for differentially expressed proteins (DEPs) that were increased in ccRCC cells compared to HEK-293 cells. Ultimately, 99 DEPs including 75 up-regulated and 24 down-regulated proteins, that were significantly altered in both ccRCC cells, were identified. Among DEPs, vimentin was identified as the most significantly changed protein. Its increased expression in ccRCC was verified through immunoblotting in ccRCC cell lines and immunohistochemistry in kidney tumors.</p><p><strong>Conclusion: </strong>From the global proteomics data detected in ccRCC, we propose 99 DEPs including vimentin as progression factors.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 6","pages":"645-652"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SF3B4 Regulates Cellular Senescence and Suppresses Therapy-induced Senescence of Cancer Cells.","authors":"Seungyeon Yang, Minbeom Ko, Soojung Claire Hur, Eun Kyung Lee, Seung Min Jeong","doi":"10.21873/cgp.20478","DOIUrl":"10.21873/cgp.20478","url":null,"abstract":"<p><strong>Background/aim: </strong>Cellular senescence is a state in which cells permanently exit the cell cycle, preventing tumor growth, but it can also contribute to aging and chronic inflammation. Senescence induced by cancer therapies, known as therapy-induced senescence (TIS), halts cancer cell proliferation and prevents metastasis. TIS has been investigated as an important therapeutic approach that could minimize cytotoxicity effects. This study aimed to elucidate the role of splicing factor 3B subunit 4 (SF3B4) in cellular senescence and TIS in cancer cells.</p><p><strong>Materials and methods: </strong>β-galactosidase staining was used to examine senescence induction. SF3B4 and p21 expression were determined by RT-qPCR and western blot. Cell proliferation and cell death were evaluated.</p><p><strong>Results: </strong>SF3B4 expression decreases in replicative senescent human fibroblasts and its knockdown induces senescence via a p21-dependent pathway. In A549 non-small cell lung cancer (NSCLC) cells, SF3B4 knockdown also increased senescence markers. Notably, SF3B4 overexpression mitigated doxorubicin-induced senescence in A549 cells.</p><p><strong>Conclusion: </strong>SF3B4 regulates senescence, and this study highlights its potential as a therapeutic target for developing better cancer treatment strategies by leveraging TIS to suppress tumor growth and enhance treatment efficacy.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 6","pages":"622-629"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppressing Expression of SERPINE1/PAI1 Through Activation of GPER1 Reduces Progression of Vulvar Carcinoma.","authors":"Tammy Doelker, Julia Gallwas, Carsten Gründker","doi":"10.21873/cgp.20473","DOIUrl":"10.21873/cgp.20473","url":null,"abstract":"<p><strong>Background/aim: </strong>The serine proteinase inhibitor 1 (SERPINE1) gene codes for the plasminogen activator inhibitor 1 (PAI1) protein and is thought to play a tumor supportive role in various cancers. In this work we aimed to uncover the role PAI1 plays in the proliferation, migration, and invasion of vulvar cancer (VC), and define the protein's function as an oncogene or tumor suppressor.</p><p><strong>Materials and methods: </strong>Through treatment with an agonist (G1) and antagonist (G36) of G-coupled estrogen receptor 1 (GPER1), an upstream regulator of SERPINE1 expression, and a forward transfection knockdown protocol, the expression of SERPINE1/PAI1 in VC cells was altered. The effects these altered SERPINE1/PAI1 levels had on tumor cell functions were then examined. Proliferation was analyzed using the resazurin assay, while migration was studied via the gap closure assay. Through colony- and tumor sphere- formation assays clonogenicity was tested, and western blots showed protein expression.</p><p><strong>Results: </strong>In A431 VC cells, when the levels of PAI1 were reduced via knockdown or treatment with G1, migration, proliferation, and colony growth was reduced. Treatment with G36 increased expression of PAI1 and increased migration and colony size in CAL39 cells.</p><p><strong>Conclusion: </strong>Based on the findings in this study, suppressing PAI1 expression in VC cells appears to reduce their progression and tumorigenic potential. Therefore, PAI1 could possibly function as an oncogene in VC. GPER1 appears to be a suitable target for suppressing PAI1 in VC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 6","pages":"566-579"},"PeriodicalIF":2.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.","authors":"Kinan Mokbel, Michael Weedon, Victoria Moye, Leigh Jackson","doi":"10.21873/cgp.20461","DOIUrl":"10.21873/cgp.20461","url":null,"abstract":"<p><strong>Background/aim: </strong>Endocrine therapy is the standard treatment for hormone receptor-positive (HR+) breast cancer (BC). Yet, it is accompanied by treatment-related toxicities, leading to poor treatment adherence, high relapse, and low rates of survival. While pharmacogenomic variants have the potential to guide personalized treatment, their predictive value is inconsistent across published studies.</p><p><strong>Materials and methods: </strong>To systematically assess the literature's current landscape of pharmacogenomics of endocrine therapy-related adverse drug effects, systematic searches in MEDLINE, Embase, Cochrane CENTRAL, Google Scholar and PharmGKB databases were conducted.</p><p><strong>Results: </strong>We identified 87 articles. Substantial heterogeneity and variability in pharmacogenomic effects were evident across studies, with many using data from the same cohorts and predominantly focusing on the Caucasian population and postmenopausal women. Meta-analyses revealed Factor V Leiden mutation as a predictor of thromboembolic events in tamoxifen-treated women (p<0.0001). Meta-analyses also found that rs7984870 and rs2234693 were associated with musculoskeletal toxicities in postmenopausal women receiving aromatase inhibitors (p<0.0001 and p<0.0001, respectively).</p><p><strong>Conclusion: </strong>Overall, the current body of evidence regarding the potential role of pharmacogenomics in endocrine therapy-related toxicity in BC remains largely inconclusive. Key concerns include the heterogeneity in toxicity definitions, lack of consideration for genotype-treatment interactions, and the failure to account for multiple testing. The review underscores the necessity for larger and well-designed studies, particularly with the inclusion of premenopausal women and non-Caucasian populations.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"421-438"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desert Hedgehog Down-regulation Mediates Inhibition of Proliferation by γ-Glutamylcyclotransferase Knockdown in Murine Glioblastoma Stem Cells.","authors":"Masaya Mori, Hiromi Ii, Mitsugu Fujita, Kozue Nose, Ayako Shimada, Risa Shiraki, Yuhi Sone, Chiami Moyama, Keiko Taniguchi, Susumu Nakata","doi":"10.21873/cgp.20465","DOIUrl":"10.21873/cgp.20465","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is the most frequent type of adult-onset malignant brain tumor and has a very poor prognosis. Glioblastoma stem cells have been shown to be one of the mechanisms by which glioblastoma acquires therapy resistance. Therefore, there is a need to establish novel therapeutic strategies useful for inhibiting this cell population. γ-Glutamylcyclotransferase (GGCT) is an enzyme involved in the synthesis and metabolism of glutathione, which is highly expressed in a wide range of cancer types, including glioblastoma, and inhibition of its expression has been reported to have antitumor effects on various cancer types. The aim of this study was to clarify the function of GGCT in glioblastoma stem cells.</p><p><strong>Materials and methods: </strong>We searched for pathways affected by GGCT overexpression in mouse embryonic fibroblasts NIH-3T3 by comprehensive gene expression analysis. Knockdown of GGCT and overexpression of desert hedgehog (DHH), a representative ligand of the pathway, were performed in glioblastoma stem cells derived from a mouse glioblastoma model.</p><p><strong>Results: </strong>GGCT overexpression activated the hedgehog pathway. Knockdown of GGCT inhibited proliferation of glioblastoma stem cells and reduced expression of DHH and the downstream target GLI family zinc finger 1 (GLI1). DHH overexpression significantly restored the growth-suppressive effect of GGCT knockdown.</p><p><strong>Conclusion: </strong>High GGCT expression is important for expression of DHH and activation of the hedgehog pathway, which is required to maintain glioblastoma stem cell proliferation. Therefore, inhibition of GGCT function may be useful in suppressing stemness of glioblastoma stem cells accompanied by activation of the hedgehog pathway.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"474-484"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Bmi1 for Enhancing Anoikis Sensitivity and Inhibiting Metastasis in Colorectal Cancer.","authors":"Yin-Chou Hsu, Chi-Wen Luo, Shu-Jyuan Chang, Chiao-Ying Lai, Yu-Tzu Yang, Yi-Zi Chen, Wang-Ta Liu, Chun-Chieh Wu, Cheuk-Kwan Sun, Ming-Feng Hou, Mei-Ren Pan","doi":"10.21873/cgp.20469","DOIUrl":"10.21873/cgp.20469","url":null,"abstract":"<p><strong>Background/aim: </strong>Patients diagnosed with advanced metastatic colorectal cancer (CRC) confront a bleak prognosis characterized by low survival rates. Anoikis, the programmed apoptosis resistance exhibited by metastatic cancer cells, is a crucial factor in this scenario.</p><p><strong>Materials and methods: </strong>We employed bulk flow cytometry and RT-qPCR assays, conducted in vivo experiments with mice and zebrafish, and analyzed patient tissues to examine the effects of the B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1)-midkine (MDK) axis on the cellular response to anoikis. Bmi1 is pivotal in tumorigenesis. This study elucidated the involvement of Bmi1 in conferring anoikis resistance in CRC and explored its downstream targets associated with metastasis.</p><p><strong>Results: </strong>Elevated levels of Bmi1 expression correlated with distant metastasis in CRC. Suppression of Bmi1 significantly diminished the metastatic potential of CRC cells. Inhibition of Bmi1 led to an increase in the proportion of apoptotic SW620 cells detached from the matrix. This effect was further enhanced by the addition of irinotecan, a topoisomerase I inhibitor. Furthermore, Bmi1 was found to synergize with MDK in modulating CRC viability, with consistent expression patterns observed in in vivo models and clinical tissue specimens. In summary, Bmi1 acted as a regulator of CRC metastatic capability by conferring anoikis resistance. Additionally, it collaborated with MDK to facilitate invasion and distant metastasis.</p><p><strong>Conclusion: </strong>Targeting Bmi1 may offer a promising adjunctive therapeutic strategy when administering traditional chemotherapy regimens to patients with advanced CRC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"523-532"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P53 Status Influences the Anti-proliferative Effect Induced by IFITM1 Inhibition in Estrogen Receptor-positive Breast Cancer Cells.","authors":"DER Sheng Sun, Jung-Sook Yoon, Yong-Seok Kim, Hye Sung Won","doi":"10.21873/cgp.20468","DOIUrl":"10.21873/cgp.20468","url":null,"abstract":"<p><strong>Background/aim: </strong>Interferon-induced trans-membrane protein 1 (IFITM1) is known to be involved in breast cancer progression. We aimed to investigate its role in estrogen receptor (ER)-positive breast cancer cells with wild-type p53 and tamoxifen-resistant breast cancer cells.</p><p><strong>Materials and methods: </strong>The ER-positive breast cancer cell lines, MCF-7 with wild-type p53 and T47D with mutant p53, were used. We established an MCF-7-derived tamoxifen-resistant cell line (TamR) by long-term culture of MCF-7 cells with 4-hydroxytamoxifen.</p><p><strong>Results: </strong>IFITM1 inhibition in MCF-7 cells significantly decreased cell growth and migration. MCF-7 cells with suppression of IFITM1 using siRNA or ruxolitinib showed reduced cell viability after tamoxifen treatment compared with that in the control MCF-7 cells. Unexpectedly, mRNA and protein levels of IFITM1 were decreased in TamR cells compared with those in MCF-7 cells. TamR cells with suppression of IFITM1 using siRNA or ruxolitinib showed no change in cell viability after treatment with tamoxifen. P53 knockdown using siRNA reduced the mRNA levels of IRF9 and increased mRNA and protein levels of SOCS3 in MCF-7 cells, suggesting that loss or mutation of p53 can affect the induction of IFITM1 via the JAK/STAT signaling pathway in breast cancer. Furthermore, MCF-7 cells with p53 knockdown using siRNA showed no decrease in cell viability after tamoxifen treatment or IFITM1 inhibition, indicating that p53 status may be important for cell death after tamoxifen treatment or IFITM1 inhibition.</p><p><strong>Conclusion: </strong>IFITM1 inhibition may enhance the sensitivity to tamoxifen based on p53-dependent enhancement of IFN signaling in wild-type p53, ER-positive breast cancer cells.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"511-522"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation in Recurrent Glioblastomas: Increased TEM8 Expression Activates the Src/PI3K/AKT/GSK-3β/B-Catenin Pathway.","authors":"Paramita Kundu, Ruchi Jain, Nandaki Nag Kanuri, Arivazhagan Arimappamagan, Vani Santosh, Paturu Kondaiah","doi":"10.21873/cgp.20466","DOIUrl":"10.21873/cgp.20466","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastomas (GBM) are infiltrative malignant brain tumors which mostly recur within a year's time following surgical resection and chemo-radiation therapy. Studies on glioblastoma cells following radio-chemotherapy, have been demonstrated to induce trans-differentiation, cellular plasticity, activation of DNA damage response and stemness. As glioblastomas are heterogenous tumors that develop treatment resistance and plasticity, we investigated if there exist genome-wide DNA methylation changes in recurrent tumors.</p><p><strong>Materials and methods: </strong>Utilizing genome-wide DNA methylation arrays, we compared the DNA methylation profile of 11 primary (first occurrence) tumors with 13 recurrent (relapsed) GBM, to delineate the contribution of epigenetic changes associated with therapy exposure, therapy resistance, and relapse of disease.</p><p><strong>Results: </strong>Our data revealed 1,224 hypermethylated- and 526 hypomethylated-probes in recurrent glioblastomas compared to primary disease. We found differential methylation of solute carrier and ion channel genes, interleukin receptor/ligand genes, tumor-suppressor genes and genes associated with metastasis. We functionally characterized one such hypomethylated-up-regulated gene, namely anthrax toxin receptor 1/tumor endothelial marker 8 (ANTXR1/TEM8), whose expression was validated to be significantly up-regulated in recurrent glioblastomas compared to primary tumors and confirmed by immunohistochemistry. Using overexpression and knockdown approaches, we showed that TEM8 induces proliferation, invasion, migration, and chemo-radioresistance in glioblastoma cells. Additionally, we demonstrated a novel mechanism of β-catenin stabilization and activation of the β-catenin transcriptional program due to TEM8 overexpression via a Src/PI3K/AKT/GSK3β/β-catenin pathway.</p><p><strong>Conclusion: </strong>We report genome-wide DNA methylation changes in recurrent GBM and suggest involvement of the TEM8 gene in GBM recurrence and progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"485-501"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells.","authors":"Taira Hirose, Yuki Kunisada, Koichi Kadoya, Hiroki Mandai, Yumi Sakamoto, Kyoichi Obata, Kisho Ono, Hiroaki Takakura, Kazuhiro Omori, Shogo Takashiba, Seiji Suga, Soichiro Ibaragi","doi":"10.21873/cgp.20464","DOIUrl":"10.21873/cgp.20464","url":null,"abstract":"<p><strong>Background/aim: </strong>Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically.</p><p><strong>Results: </strong>Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models.</p><p><strong>Conclusion: </strong>This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"464-473"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impacts of Matrix Metalloproteinase-2 Promoter Genotypes on Breast Cancer Risk.","authors":"Chih-Chiang Hung, Chung-Lin Tsai, Yu-Ting Chin, Yun-Chi Wang, Chia-Hua Liu, Meng-Liang Lin, Shih-Shun Chen, Jie-Long He, Chia-Wen Tsai, Chen-Hsien Su, DA-Tian Bau, Wen-Shin Chang","doi":"10.21873/cgp.20467","DOIUrl":"10.21873/cgp.20467","url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk.</p><p><strong>Materials and methods: </strong>MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls.</p><p><strong>Results: </strong>Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05).</p><p><strong>Conclusion: </strong>MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"21 5","pages":"502-510"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}