Mary L Fay, Chris Nicol, Christine Orr, Brooke Wilson, David Hurlbut, Harriet Feilotter, Scott Davey
{"title":"未折叠蛋白反应的下调将二甲双胍治疗与结直肠癌患者的良好临床结果联系起来。","authors":"Mary L Fay, Chris Nicol, Christine Orr, Brooke Wilson, David Hurlbut, Harriet Feilotter, Scott Davey","doi":"10.3390/curroncol32030138","DOIUrl":null,"url":null,"abstract":"<p><p>Type 2 diabetes is a risk factor for colorectal cancer (CRC) development and progression. However, metformin-treated diabetic CRC patients tend to have better clinical outcomes than those managed by other means. To better characterize the molecular underpinnings of metformin's protective effects, we performed a targeted transcriptomic analysis of primary CRC tissue samples (<i>n</i> = 272). A supervised learning algorithm pinpointed molecular features that discriminate between metformin-treated and diet-controlled diabetic CRC samples, as well as those that discriminated between non-diabetic samples based on their five-year overall survival status. Our results show downregulation of TMEM132 in metformin-treated samples (<i>p</i> = 0.05) and non-diabetics with good clinical outcomes (<i>p</i> = 0.05) relative to diet-controlled and non-diabetics with poor survival, respectively. Furthermore, upregulation of SCNN1A is observed in metformin-treated samples (<i>p</i> = 0.04) and non-diabetics with good clinical outcomes (<i>p</i> = 0.01) relative to diet-controlled samples and those with poor clinical outcomes, respectively. We also show that the antiapoptotic protein sFas is downregulated in metformin-treated samples relative to diet-controlled samples (<i>p</i> = 0.005). These findings suggest a role for the unfolded protein response in mediating metformin-related CRC-protective effects by enhancing apoptosis and suggest the investigation of these proteins as targets for novel CRC therapies.</p>","PeriodicalId":11012,"journal":{"name":"Current oncology","volume":"32 3","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941617/pdf/","citationCount":"0","resultStr":"{\"title\":\"Downregulation of the Unfolded Protein Response Links Metformin Treatment to Good Clinical Outcomes in Colorectal Cancer Patients.\",\"authors\":\"Mary L Fay, Chris Nicol, Christine Orr, Brooke Wilson, David Hurlbut, Harriet Feilotter, Scott Davey\",\"doi\":\"10.3390/curroncol32030138\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Type 2 diabetes is a risk factor for colorectal cancer (CRC) development and progression. However, metformin-treated diabetic CRC patients tend to have better clinical outcomes than those managed by other means. To better characterize the molecular underpinnings of metformin's protective effects, we performed a targeted transcriptomic analysis of primary CRC tissue samples (<i>n</i> = 272). A supervised learning algorithm pinpointed molecular features that discriminate between metformin-treated and diet-controlled diabetic CRC samples, as well as those that discriminated between non-diabetic samples based on their five-year overall survival status. Our results show downregulation of TMEM132 in metformin-treated samples (<i>p</i> = 0.05) and non-diabetics with good clinical outcomes (<i>p</i> = 0.05) relative to diet-controlled and non-diabetics with poor survival, respectively. Furthermore, upregulation of SCNN1A is observed in metformin-treated samples (<i>p</i> = 0.04) and non-diabetics with good clinical outcomes (<i>p</i> = 0.01) relative to diet-controlled samples and those with poor clinical outcomes, respectively. We also show that the antiapoptotic protein sFas is downregulated in metformin-treated samples relative to diet-controlled samples (<i>p</i> = 0.005). These findings suggest a role for the unfolded protein response in mediating metformin-related CRC-protective effects by enhancing apoptosis and suggest the investigation of these proteins as targets for novel CRC therapies.</p>\",\"PeriodicalId\":11012,\"journal\":{\"name\":\"Current oncology\",\"volume\":\"32 3\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-02-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941617/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/curroncol32030138\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/curroncol32030138","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Downregulation of the Unfolded Protein Response Links Metformin Treatment to Good Clinical Outcomes in Colorectal Cancer Patients.
Type 2 diabetes is a risk factor for colorectal cancer (CRC) development and progression. However, metformin-treated diabetic CRC patients tend to have better clinical outcomes than those managed by other means. To better characterize the molecular underpinnings of metformin's protective effects, we performed a targeted transcriptomic analysis of primary CRC tissue samples (n = 272). A supervised learning algorithm pinpointed molecular features that discriminate between metformin-treated and diet-controlled diabetic CRC samples, as well as those that discriminated between non-diabetic samples based on their five-year overall survival status. Our results show downregulation of TMEM132 in metformin-treated samples (p = 0.05) and non-diabetics with good clinical outcomes (p = 0.05) relative to diet-controlled and non-diabetics with poor survival, respectively. Furthermore, upregulation of SCNN1A is observed in metformin-treated samples (p = 0.04) and non-diabetics with good clinical outcomes (p = 0.01) relative to diet-controlled samples and those with poor clinical outcomes, respectively. We also show that the antiapoptotic protein sFas is downregulated in metformin-treated samples relative to diet-controlled samples (p = 0.005). These findings suggest a role for the unfolded protein response in mediating metformin-related CRC-protective effects by enhancing apoptosis and suggest the investigation of these proteins as targets for novel CRC therapies.
期刊介绍：
Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease.
We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.
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