Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors.
Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors.
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DOI：
10.1038/s41598-021-82221-4
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发表时间：
2021-01-28
影响因子：
4.6
通讯作者：
Creighton CJ
中科院分区：
文献类型：
--
作者：
Chen F;Zhang Y;Sucgang R;Ramani S;Corry D;Kheradmand F;Creighton CJ
迫切需要更深入地了解SARS-CoV-2感染的分子生物学，包括宿主对该病毒的反应。宿主对病毒感染和癌症的免疫反应存在共性。在这里，我们定义了SARS-CoV-2感染的转录特征，涉及肺腺癌细胞系（A549, Calu-3）和正常人支气管上皮细胞（NHBE）中常见的数百个基因，以及特定于一种或两种腺癌细胞系的额外特征。交叉检查8个转录组学数据库，我们发现肺腺癌细胞对SARS-CoV-2感染的宿主转录反应与不同模型系统和患者样本中宿主对多种病毒的反应具有广泛的相似性。此外，这些SARS-CoV-2转录特征在人类癌症的特定亚群中表现出来，涉及范围广泛的组织病理类型中约20%的病例。这些癌症亚群表现出免疫细胞浸润和炎症，并涉及与SARS-CoV-2反应相关的途径，如免疫检查点、IL-6、II型干扰素信号传导和NF-κB。细胞系数据代表了肿瘤癌细胞内特异性激活的免疫反应。作为病毒宿主反应一部分的常见基因和途径指向可能适用于SARS-CoV-2和癌症的治疗策略。
A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.
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影响因子：
7.7
作者：
Zamorano Cuervo N;Grandvaux N
通讯作者：
Grandvaux N
影响因子：
30.5
作者：
Altman, Matthew C.;Gill, Michelle A.;Jackson, Daniel J.
通讯作者：
Jackson, Daniel J.
影响因子：
3.7
作者：
Creighton CJ;Hernandez-Herrera A;Jacobsen A;Levine DA;Mankoo P;Schultz N;Du Y;Zhang Y;Larsson E;Sheridan R;Xiao W;Spellman PT;Getz G;Wheeler DA;Perou CM;Gibbs RA;Sander C;Hayes DN;Gunaratne PH;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bell, D.;Berchuck, A.;Birrer, M.;Chien, J.;Cramer, D. W.;Dao, F.;Dhir, R.;DiSaia, P.;Gabra, H.;Glenn, P.;Godwin, A. K.;Gross, J.;Hartmann, L.;Huang, M.;Huntsman, D. G.;Iacocca, M.;Imielinski, M.;Kalloger, S.;Karlan, B. Y.;Levine, D. A.;Mills, G. B.;Morrison, C.;Mutch, D.;Olvera, N.;Orsulic, S.;Park, K.;Petrelli, N.;Rabeno, B.;Rader, J. S.;Sikic, B. I.;Smith-McCune, K.;Sood, A. K.;Bowtell, D.;Penny, R.;Testa, J. R.;Chang, K.;Dinh, H. H.;Drummond, J. A.;Fowler, G.;Gunaratne, P.;Hawes, A. C.;Kovar, C. L.;Lewis, L. R.;Morgan, M. B.;Newsham, I. F.;Santibanez, J.;Reid, J. G.;Trevino, L. R.;Wu, Y. -Q.;Wang, M.;Muzny, D. M.;Wheeler, D. A.;Gibbs, R. A.;Getz, G.;Lawrence, M. S.;Cibulskis, K.;Sivachenko, A. Y.;Sougnez, C.;Voet, D.;Wilkinson, J.;Bloom, T.;Ardlie, K.;Fennell, T.;Baldwin, J.;Gabriel, S.;Lander, E. S.;Ding, L.;Fulton, R. S.;Koboldt, D. C.;McLellan, M. D.;Wylie, T.;Walker, J.;O'Laughlin, M.;Dooling, D. J.;Fulton, L.;Abbott, R.;Dees, N. D.;Zhang, Q.;Kandoth, C.;Wendl, M.;Schierding, W.;Shen, D.;Harris, C. C.;Schmidt, H.;Kalicki, J.;Delehaunty, K. D.;Fronick, C. C.;Demeter, R.;Cook, L.;Wallis, J. W.;Lin, L.;Magrini, V. J.;Hodges, J. S.;Eldred, J. M.;Smith, S. M.;Pohl, C. S.;Vandin, F.;Raphael, B. J.;Weinstock, G. M.;Mardis, R.;Wilson, R. K.;Meyerson, M.;Winckler, W.;Getz, G.;Verhaak, R. G. W.;Carter, S. L.;Mermel, C. H.;Saksena, G.;Nguyen, H.;Onofrio, R. C.;Lawrence, M. S.;Hubbard, D.;Gupta, S.;Crenshaw, A.;Ramos, A. H.;Ardlie, K.;Chin, L.;Protopopov, A.;Zhang, Juinhua;Kim, T. M.;Perna, I.;Xiao, Y.;Zhang, H.;Ren, G.;Sathiamoorthy, N.;Park, R. W.;Lee, E.;Park, P. J.;Kucherlapati, R.;Absher, D. M.;Waite, L.;Sherlock, G.;Brooks, J. D.;Li, J. Z.;Xu, J.;Myers, R. M.;Laird, P. W.;Cope, L.;Herman, J. G.;Shen, H.;Weisenberger, D. J.;Noushmehr, H.;Pan, F.;Triche, T., Jr.;Berman, B. P.;Van den Berg, D. J.;Buckley, J.;Baylin, S. B.;Spellman, P. T.;Purdom, E.;Neuvial, P.;Bengtsson, H.;Jakkula, L. R.;Durinck, S.;Han, J.;Dorton, S.;Marr, H.;Choi, Y. G.;Wang, V.;Wang, N. J.;Ngai, J.;Conboy, J. G.;Parvin, B.;Feiler, H. S.;Speed, T. P.;Gray, J. W.;Levine, D. A.;Socci, N. D.;Liang, Y.;Taylor, B. S.;Schultz, N.;Borsu, L.;Lash, A. E.;Brennan, C.;Viale, A.;Sander, C.;Ladanyi, M.;Hoadley, K. A.;Meng, S.;Du, Y.;Shi, Y.;Li, L.;Turman, Y. J.;Zang, D.;Helms, E. B.;Balu, S.;Zhou, X.;Wu, J.;Topal, M. D.;Hayes, D. N.;Perou, C. M.;Getz, G.;Voet, D.;Saksena, G.;Zhang, Junihua;Zhang, H.;Wu, C. J.;Shukla, S.;Cibulskis, K.;Lawrence, M. S.;Sivachenko, A.;Jing, R.;Park, R. W.;Liu, Y.;Park, P. J.;Noble, M.;Chin, L.;Carter, H.;Kim, D.;Karchin, R.;Spellman, P. T.;Purdom, E.;Neuvial, P.;Bengtsson, H.;Durinck, S.;Han, J.;Korkola, J. E.;Heiser, L. M.;Cho, R. J.;Hu, Z.;Parvin, B.;Speed, T. P.;Gray, J. W.;Schultz, N.;Cerami, E.;Taylor, B. S.;Olshen, A.;Reva, B.;Antipin, Y.;Shen, R.;Mankoo, P.;Sheridan, R.;Ciriello, G.;Chang, W. K.;Bernanke, J. A.;Borsu, L.;Levine, D. A.;Ladanyi, M.;Sander, C.;Haussler, D.;Benz, C. C.;Stuart, J. M.;Benz, S. C.;Sanborn, J. Z.;Vaske, C. J.;Zhu, J.;Szeto, C.;Scott, G. K.;Yau, C.;Hoadley, K. A.;Du, Y.;Balu, S.;Hayes, D. N.;Perou, C. M.;Wilkerson, M. D.;Zhang, N.;Akbani, R.;Baggerly, K. A.;Yung, W. K.;Mills, G. B.;Weinstein, J. N.;Penny, R.;Shelton, T.;Grimm, D.;Hatfield, M.;Morris, S.;Yena, P.;Rhodes, P.;Sherman, M.;Paulauskis, J.;Millis, S.;Kahn, A.;Greene, J. M.;Sfeir, R.;Jensen, M. A.;Chen, J.;Whitmore, J.;Alonso, S.;Jordan, J.;Chu, A.;Zhang, Jinghui;Barker, A.;Compton, C.;Eley, G.;Ferguson, M.;Fielding, P.;Gerhard, D. S.;Myles, R.;Schaefer, C.;Shaw, K. R. Mills;Vaught, J.;Vockley, J. B.;Good, P. J.;Guyer, M. S.;Ozenberger, B.;Peterson, J.;Thomson, E.
通讯作者：
Thomson, E.