Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients.
Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients.
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对胎盘侵袭的抵抗力的进化增加了黑色素瘤患者的生存率。
DOI：
10.3390/jcm10040595
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发表时间：
2021-02-05
影响因子：
3.9
通讯作者：
Kshitiz
中科院分区：
文献类型：
--
作者：
Suhail Y;Afzal J;Kshitiz
尽管肿瘤形成率可能相似，但哺乳动物的癌症恶性率存在很大差异。在胎盘哺乳动物中，恶性肿瘤的发生率与胎盘侵袭的程度相关。我们的侵袭水平进化（ELI）框架将这两种现象联系起来，识别出可能赋予基质成纤维细胞抵抗力以限制子宫内膜滋养层细胞和皮肤中播散性黑色素瘤侵袭的基因。在此，利用癌症基因组图谱 (TCGA) 的患者数据，我们报告这些抗侵袭基因可能对人类患者黑色素瘤的进展至关重要，并且它们的丢失与癌症扩散增加和生存率降低相关。令人惊讶的是，我们的结果表明，与非侵入性胎盘物种相比，这些抗侵入基因在人类中的表达较低，可能会阻止间质侵入，而其水平的进一步降低会增加黑色素瘤的恶性程度和致死率。我们的工作将进化、比较生物学和跨组织的癌症进展联系起来，表明了使用进化医学预测和治疗人类癌症的新途径。
Mammals exhibit large differences in rates of cancer malignancy, even though the tumor formation rates may be similar. In placental mammals, rates of malignancy correlate with the extent of placental invasion. Our Evolved Levels of Invasibility (ELI) framework links these two phenomena identifying genes that potentially confer resistance in stromal fibroblasts to limit invasion, from trophoblasts in the endometrium, and from disseminating melanoma in the skin. Herein, using patient data from The Cancer Genome Atlas (TCGA), we report that these anti-invasive genes may be crucial in melanoma progression in human patients, and that their loss is correlated with increased cancer spread and lowered survival. Our results suggest that, surprisingly, these anti-invasive genes, which have lower expression in humans compared to species with non-invasive placentation, may potentially prevent stromal invasion, while a further reduction in their levels increases the malignancy and lethality of melanoma. Our work links evolution, comparative biology, and cancer progression across tissues, indicating new avenues for using evolutionary medicine to prognosticate and treat human cancers.
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影响因子：
3.1
作者：
Li X;Ma Q;Xu Q;Duan W;Lei J;Wu E
通讯作者：
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影响因子：
78.5
作者：
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通讯作者：
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影响因子：
3.9
作者：
Hu G;Xu F;Zhong K;Wang S;Huang L;Chen W
通讯作者：
Chen W
影响因子：
30.8
作者：
Lonsdale, John;Thomas, Jeffrey;Salvatore, Mike;Phillips, Rebecca;Lo, Edmund;Shad, Saboor;Hasz, Richard;Walters, Gary;Garcia, Fernando;Young, Nancy;Foster, Barbara;Moser, Mike;Karasik, Ellen;Gillard, Bryan;Ramsey, Kimberley;Sullivan, Susan;Bridge, Jason;Magazine, Harold;Syron, John;Fleming, Johnelle;Siminoff, Laura;Traino, Heather;Mosavel, Maghboeba;Barker, Laura;Jewell, Scott;Rohrer, Dan;Maxim, Dan;Filkins, Dana;Harbach, Philip;Cortadillo, Eddie;Berghuis, Bree;Turner, Lisa;Hudson, Eric;Feenstra, Kristin;Sobin, Leslie;Robb, James;Branton, Phillip;Korzeniewski, Greg;Shive, Charles;Tabor, David;Qi, Liqun;Groch, Kevin;Nampally, Sreenath;Buia, Steve;Zimmerman, Angela;Smith, Anna;Burges, Robin;Robinson, Karna;Valentino, Kim;Bradbury, Deborah;Cosentino, Mark;Diaz-Mayoral, Norma;Kennedy, Mary;Engel, Theresa;Williams, Penelope;Erickson, Kenyon;Ardlie, Kristin;Winckler, Wendy;Getz, Gad;DeLuca, David;MacArthur, Daniel;Kellis, Manolis;Thomson, Alexander;Young, Taylor;Gelfand, Ellen;Donovan, Molly;Meng, Yan;Grant, George;Mash, Deborah;Marcus, Yvonne;Basile, Margaret;Liu, Jun;Zhu, Jun;Tu, Zhidong;Cox, Nancy J.;Nicolae, Dan L.;Gamazon, Eric R.;Im, Hae Kyung;Konkashbaev, Anuar;Pritchard, Jonathan;Stevens, Matthew;Flutre, Timothee;Wen, Xiaoquan;Dermitzakis, Emmanouil T.;Lappalainen, Tuuli;Guigo, Roderic;Monlong, Jean;Sammeth, Michael;Koller, Daphne;Battle, Alexis;Mostafavi, Sara;McCarthy, Mark;Rivas, Manual;Maller, Julian;Rusyn, Ivan;Nobel, Andrew;Wright, Fred;Shabalin, Andrey;Feolo, Mike;Sharopova, Nataliya;Sturcke, Anne;Paschal, Justin;Anderson, James M.;Wilder, Elizabeth L.;Derr, Leslie K.;Green, Eric D.;Struewing, Jeffery P.;Temple, Gary;Volpi, Simona;Boyer, Joy T.;Thomson, Elizabeth J.;Guyer, Mark S.;Cathy Ng;Abdallah, Assya;Colantuoni, Deborah;Insel, Thomas R.;Koester, Susan E.;Little, A. Roger;Bender, Patrick K.;Lehner, Thomas;Yao, Yin;Compton, Carolyn C.;Vaught, Jimmie B.;Sawyer, Sherilyn;Lockhart, Nicole C.;Demchok, Joanne;Moore, Helen F.
通讯作者：
Moore, Helen F.