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1. Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome

Author

Strand, Siri H., Houlahan, Kathleen E., Branch, Vernal, Lynch, Thomas, Rivero-Guitiérrez, Belén, Harmon, Bryan, Couch, Fergus, Gallagher, Kristalyn, Kilgore, Mark, Wei, Shi, DeMichele, Angela, King, Tari, McAuliffe, Priscilla, Curtis, Christina, Owzar, Kouros, Marks, Jeffrey R., Colditz, Graham A., Hwang, E. Shelley, and West, Robert B.

Published
2024
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2. Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors

Author

Llinàs-Arias, Pere, Ensenyat-Mendez, Miquel, Íñiguez-Muñoz, Sandra, Orozco, Javier I. J., Valdez, Betsy, Salomon, Matthew P., Matsuba, Chikako, Solivellas-Pieras, Maria, Bedoya-López, Andrés F., Sesé, Borja, Mezger, Anja, Ormestad, Mattias, Unzueta, Fernando, Strand, Siri H., Boiko, Alexander D., Hwang, E Shelley, Cortés, Javier, DiNome, Maggie L., Esteller, Manel, Lupien, Mathieu, and Marzese, Diego M.

Published
2023
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3. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Author

Strand, Siri H., Rivero-Gutiérrez, Belén, Houlahan, Kathleen E., Seoane, Jose A., King, Lorraine M., Risom, Tyler, Simpson, Lunden A., Vennam, Sujay, Khan, Aziz, Cisneros, Luis, Hardman, Timothy, Harmon, Bryan, Couch, Fergus, Gallagher, Kristalyn, Kilgore, Mark, Wei, Shi, DeMichele, Angela, King, Tari, McAuliffe, Priscilla F., Nangia, Julie, Lee, Joanna, Tseng, Jennifer, Storniolo, Anna Maria, Thompson, Alastair M., Gupta, Gaorav P., Burns, Robyn, Veis, Deborah J., DeSchryver, Katherine, Zhu, Chunfang, Matusiak, Magdalena, Wang, Jason, Zhu, Shirley X., Tappenden, Jen, Ding, Daisy Yi, Zhang, Dadong, Luo, Jingqin, Jiang, Shu, Varma, Sushama, Anderson, Lauren, Straub, Cody, Srivastava, Sucheta, Curtis, Christina, Tibshirani, Rob, Angelo, Robert Michael, Hall, Allison, Owzar, Kouros, Polyak, Kornelia, Maley, Carlo, Marks, Jeffrey R., Colditz, Graham A., Hwang, E. Shelley, and West, Robert B.

Published
2022
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4. Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

Author

Risom, Tyler, Glass, David R., Averbukh, Inna, Liu, Candace C., Baranski, Alex, Kagel, Adam, McCaffrey, Erin F., Greenwald, Noah F., Rivero-Gutiérrez, Belén, Strand, Siri H., Varma, Sushama, Kong, Alex, Keren, Leeat, Srivastava, Sucheta, Zhu, Chunfang, Khair, Zumana, Veis, Deborah J., Deschryver, Katherine, Vennam, Sujay, Maley, Carlo, Hwang, E. Shelley, Marks, Jeffrey R., Bendall, Sean C., Colditz, Graham A., West, Robert B., and Angelo, Michael

Published
2022
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5. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Aberle, Denise, Achilefu, Samuel I., Ademuyiwa, Foluso O., Adey, Andrew C., Aft, Rebecca L., Agarwal, Rachana, Aguilar, Ruben A., Alikarami, Fatemeh, Allaj, Viola, Amos, Christopher, Anders, Robert A., Angelo, Michael R., Anton, Kristen, Ashenberg, Orr, Aster, Jon C., Babur, Ozgun, Bahmani, Amir, Balsubramani, Akshay, Barrett, David, Beane, Jennifer, Bender, Diane E., Bernt, Kathrin, Berry, Lynne, Betts, Courtney B., Bletz, Julie, Blise, Katie, Boire, Adrienne, Boland, Genevieve, Borowsky, Alexander, Bosse, Kristopher, Bott, Matthew, Boyden, Ed, Brooks, James, Bueno, Raphael, Burlingame, Erik A., Cai, Qiuyin, Campbell, Joshua, Caravan, Wagma, Cerami, Ethan, Chaib, Hassan, Chan, Joseph M., Chang, Young Hwan, Chatterjee, Deyali, Chaudhary, Ojasvi, Chen, Alyce A., Chen, Bob, Chen, Changya, Chen, Chia-hui, Chen, Feng, Chen, Yu-An, Chheda, Milan G., Chin, Koei, Chiu, Roxanne, Chu, Shih-Kai, Chuaqui, Rodrigo, Chun, Jaeyoung, Cisneros, Luis, Coffey, Robert J., Colditz, Graham A., Cole, Kristina, Collins, Natalie, Contrepois, Kevin, Coussens, Lisa M., Creason, Allison L., Crichton, Daniel, Curtis, Christina, Davidsen, Tanja, Davies, Sherri R., de Bruijn, Ino, Dellostritto, Laura, De Marzo, Angelo, Demir, Emek, DeNardo, David G., Diep, Dinh, Ding, Li, Diskin, Sharon, Doan, Xengie, Drewes, Julia, Dubinett, Stephen, Dyer, Michael, Egger, Jacklynn, Eng, Jennifer, Engelhardt, Barbara, Erwin, Graham, Esplin, Edward D., Esserman, Laura, Felmeister, Alex, Feiler, Heidi S., Fields, Ryan C., Fisher, Stephen, Flaherty, Keith, Flournoy, Jennifer, Ford, James M., Fortunato, Angelo, Frangieh, Allison, Frye, Jennifer L., Fulton, Robert S., Galipeau, Danielle, Gan, Siting, Gao, Jianjiong, Gao, Long, Gao, Peng, Gao, Vianne R., Geiger, Tim, George, Ajit, Getz, Gad, Ghosh, Sharmistha, Giannakis, Marios, Gibbs, David L., Gillanders, William E., Goecks, Jeremy, Goedegebuure, Simon P., Gould, Alanna, Gowers, Kate, Gray, Joe W., Greenleaf, William, Gresham, Jeremy, Guerriero, Jennifer L., Guha, Tuhin K., Guimaraes, Alexander R., Guinney, Justin, Gutman, David, Hacohen, Nir, Hanlon, Sean, Hansen, Casey R., Harismendy, Olivier, Harris, Kathleen A., Hata, Aaron, Hayashi, Akimasa, Heiser, Cody, Helvie, Karla, Herndon, John M., Hirst, Gilliam, Hodi, Frank, Hollmann, Travis, Horning, Aaron, Hsieh, James J., Hughes, Shannon, Huh, Won Jae, Hunger, Stephen, Hwang, Shelley E., Iacobuzio-Donahue, Christine A., Ijaz, Heba, Izar, Benjamin, Jacobson, Connor A., Janes, Samuel, Jané-Valbuena, Judit, Jayasinghe, Reyka G., Jiang, Lihua, Johnson, Brett E., Johnson, Bruce, Ju, Tao, Kadara, Humam, Kaestner, Klaus, Kagan, Jacob, Kalinke, Lukas, Keith, Robert, Khan, Aziz, Kibbe, Warren, Kim, Albert H., Kim, Erika, Kim, Junhyong, Kolodzie, Annette, Kopytra, Mateusz, Kotler, Eran, Krueger, Robert, Krysan, Kostyantyn, Kundaje, Anshul, Ladabaum, Uri, Lake, Blue B., Lam, Huy, Laquindanum, Rozelle, Lau, Ken S., Laughney, Ashley M., Lee, Hayan, Lenburg, Marc, Leonard, Carina, Leshchiner, Ignaty, Levy, Rochelle, Li, Jerry, Lian, Christine G., Lim, Kian-Huat, Lin, Jia-Ren, Lin, Yiyun, Liu, Qi, Liu, Ruiyang, Lively, Tracy, Longabaugh, William J.R., Longacre, Teri, Ma, Cynthia X., Macedonia, Mary Catherine, Madison, Tyler, Maher, Christopher A., Maitra, Anirban, Makinen, Netta, Makowski, Danika, Maley, Carlo, Maliga, Zoltan, Mallo, Diego, Maris, John, Markham, Nick, Marks, Jeffrey, Martinez, Daniel, Mashl, Robert J., Masilionais, Ignas, Mason, Jennifer, Massagué, Joan, Massion, Pierre, Mattar, Marissa, Mazurchuk, Richard, Mazutis, Linas, Mazzilli, Sarah A., McKinley, Eliot T., McMichael, Joshua F., Merrick, Daniel, Meyerson, Matthew, Miessner, Julia R., Mills, Gordon B., Mills, Meredith, Mondal, Suman B., Mori, Motomi, Mori, Yuriko, Moses, Elizabeth, Mosse, Yael, Muhlich, Jeremy L., Murphy, George F., Navin, Nicholas E., Nawy, Tal, Nederlof, Michel, Ness, Reid, Nevins, Stephanie, Nikolov, Milen, Nirmal, Ajit Johnson, Nolan, Garry, Novikov, Edward, Oberdoerffer, Philipp, O’Connell, Brendan, Offin, Michael, Oh, Stephen T., Olson, Anastasiya, Ooms, Alex, Ossandon, Miguel, Owzar, Kouros, Parmar, Swapnil, Patel, Tasleema, Patti, Gary J., Pe’er, Dana, Pe'er, Itsik, Peng, Tao, Persson, Daniel, Petty, Marvin, Pfister, Hanspeter, Polyak, Kornelia, Pourfarhangi, Kamyar, Puram, Sidharth V., Qiu, Qi, Quintanal-Villalonga, Álvaro, Raj, Arjun, Ramirez-Solano, Marisol, Rashid, Rumana, Reeb, Ashley N., Regev, Aviv, Reid, Mary, Resnick, Adam, Reynolds, Sheila M., Riesterer, Jessica L., Rodig, Scott, Roland, Joseph T., Rosenfield, Sonia, Rotem, Asaf, Roy, Sudipta, Rozenblatt-Rosen, Orit, Rudin, Charles M., Ryser, Marc D., Santagata, Sandro, Santi-Vicini, Maria, Sato, Kazuhito, Schapiro, Denis, Schrag, Deborah, Schultz, Nikolaus, Sears, Cynthia L., Sears, Rosalie C., Sen, Subrata, Sen, Triparna, Shalek, Alex, Sheng, Jeff, Sheng, Quanhu, Shoghi, Kooresh I., Shrubsole, Martha J., Shyr, Yu, Sibley, Alexander B., Siex, Kiara, Simmons, Alan J., Singer, Dinah S., Sivagnanam, Shamilene, Slyper, Michal, Snyder, Michael P., Sokolov, Artem, Song, Sheng-Kwei, Sorger, Peter K., Southard-Smith, Austin, Spira, Avrum, Srivastava, Sudhir, Stein, Janet, Storm, Phillip, Stover, Elizabeth, Strand, Siri H., Su, Timothy, Sudar, Damir, Sullivan, Ryan, Surrey, Lea, Suvà, Mario, Tan, Kai, Terekhanova, Nadezhda V., Ternes, Luke, Thammavong, Lisa, Thibault, Guillaume, Thomas, George V., Thorsson, Vésteinn, Todres, Ellen, Tran, Linh, Tyler, Madison, Uzun, Yasin, Vachani, Anil, Van Allen, Eliezer, Vandekar, Simon, Veis, Deborah J., Vigneau, Sébastien, Vossough, Arastoo, Waanders, Angela, Wagle, Nikhil, Wang, Liang-Bo, Wendl, Michael C., West, Robert, Williams, Elizabeth H., Wu, Chi-yun, Wu, Hao, Wu, Hung-Yi, Wyczalkowski, Matthew A., Xie, Yubin, Yang, Xiaolu, Yapp, Clarence, Yu, Wenbao, Yuan, Yinyin, Zhang, Dadong, Zhang, Kun, Zhang, Mianlei, Zhang, Nancy, Zhang, Yantian, Zhao, Yanyan, Zhou, Daniel Cui, Zhou, Zilu, Zhu, Houxiang, Zhu, Qin, Zhu, Xiangzhu, Zhu, Yuankun, Zhuang, Xiaowei, Hupalowska, Anna, Rood, Jennifer E., Hanlon, Sean E., Hughes, Shannon K., Hwang, E. Shelley, Johnson, Bruce E., Shalek, Alex K., Spira, Avrum E., and West, Robert B.

Published
2020
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6. FRMD6 has tumor suppressor functions in prostate cancer

Author

Haldrup, Jakob, Strand, Siri H., Cieza-Borrella, Clara, Jakobsson, Magnus E., Riedel, Maria, Norgaard, Maibritt, Hedensted, Stine, Dagnaes-Hansen, Frederik, Ulhoi, Benedicte Parm, Eeles, Rosalind, Borre, Michael, Olsen, Jesper V., Thomsen, Martin, Kote-Jarai, Zsofia, and Sorensen, Karina D.

Published
2021
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8. Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Alterations in Epithelial Integrity

Author

Qin, Xiaodi, primary, Strand, Siri H, additional, Lee, Marissa R., additional, van Ijzendoorn, David G. P., additional, Zhu, ChunFang, additional, Vennam, Sujay, additional, Varma, Sushama, additional, Hall, Allison, additional, King, Lorraine, additional, Simpson, Lunden, additional, Luo, Xiaoke, additional, Colditz, Graham A., additional, Jiang, Shu, additional, Hwang, E. Shelley, additional, Marks, Jeffrey R., additional, Owzar, Kouros, additional, and West, Robert B., additional

Published
2023
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9. Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome

Author

Strand, Siri H., primary, Houlahan, Kathleen E., additional, Branch, Vernal, additional, Lynch, Thomas, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla, additional, Curtis, Christina, additional, Owzar, Kouros, additional, Marks, Jeffrey R., additional, Colditz, Graham A., additional, Hwang, E. Shelley, additional, and West, Robert B., additional

Published
2023
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12. Abstract P1-07-02: Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS

Author

Liu, Ying, primary, Strand, Siri H., additional, King, Lorraine, additional, Harmon, Bryan, additional, Couch, Fergus J., additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla F., additional, Marks, Jeffrey, additional, Maley, Carlo, additional, West, Robert, additional, Hwang, E Shelley, additional, and Colditz, Graham A., additional

Published
2023
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13. Abstract P2-21-03: Unique Collagen Peptide Signatures between Ductal Carcinoma in Situ and Invasive Breast Cancer by Mass Spectrometry Tissue Imaging

Author

Hulahan, Taylor S., primary, Wallace, Elizabeth N., additional, Strand, Siri H., additional, Colditz, Graham A., additional, Hwang, E Shelley, additional, West, Robert, additional, Spruill, Laura, additional, Marks, Jeffrey, additional, Drake, Richard R., additional, and Angel, Peggi M., additional

Published
2023
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15. Abstract B019: Discrete regulation of the collagen proteome among pathological features in DCIS and invasive breast cancer by mass spectrometry tissue imaging

Author

Hulahan, Taylor S., primary, Wallace, Elizabeth N., additional, Strand, Siri H., additional, Angelo, Robert Michael, additional, Colditz, Graham, additional, Hwang, Eun-Sil Shelley, additional, West, Robert, additional, Spruill, Laura, additional, Marks, Jeffrey R., additional, Drake, Richard R., additional, and Angel, Peggi M., additional

Published
2022
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18. Abstract GS4-07: The Breast PreCancer Atlas DCIS genomic signatures define biology and correlate with clinical outcomes: An analysis of TBCRC 038 and RAHBT cohorts

Author

Strand, Siri H, primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E, additional, Seoane, Jose A, additional, King, Lorraine M, additional, Risom, Tyler, additional, Simpson, Lunden, additional, Vennam, Sujay, additional, Khan, Aziz, additional, Hardman, Timothy, additional, Harmon, Bryan E, additional, Couch, Fergus J, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla F, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Anna Maria, additional, Thompson, Alastair, additional, Gupta, Gaorav, additional, Burns, Robyn, additional, Veis, Deborah J, additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X, additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R, additional, Colditz, Graham A, additional, Hwang, E Shelley, additional, and West, Robert B, additional

Published
2022
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19. DCIS genomic signatures define biology and clinical outcome: Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts

Author

Strand, Siri H, primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E, additional, Seoane, Jose A, additional, King, Lorraine M, additional, Risom, Tyler, additional, Simpson, Lunden A, additional, Vennam, Sujay, additional, Khan, Aziz, additional, Cisneros, Luis, additional, Hardman, Timothy, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla F, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Anna Maria, additional, Thompson, Alastair M, additional, Gupta, Gaorav P, additional, Burns, Robyn, additional, Veis, Deborah J, additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X, additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Anderson, Lauren, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R, additional, Colditz, Graham A, additional, Hwang, E Shelley, additional, and West, Robert B, additional

Published
2021
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20. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts

Author

Strand, Siri H., Rivero-Gutiérrez, Belén, Houlahan, Kathleen E., Seoane, Jose A., King, Lorraine M., Risom, Tyler, Simpson, Lunden A., Vennam, Sujay, Khan, Aziz, Cisneros, Luis, Hardman, Timothy, Harmon, Bryan, Couch, Fergus, Gallagher, Kristalyn, Kilgore, Mark, We, Shi, DeMichele, Angela, King, Tari, McAuliffe, Priscilla F., Nangia, Julie, Lee, Joanna, Tseng, Jennifer, Storniolo, Anna Maria, Thompson, Alastair M., Gupta, Gaorav P., Burns, Robyn, Veis, Deborah J., DeSchryver, Katherine, Zhu, Chunfang, Matusiak, Magdalena, Wang, Jason, Zhu, Shirley X., Tappenden, Jen, Ding, Daisy Yi, Zhang, Dadong, Luo, Jingqin, Jiang, Shu, Varma, Sushama, Anderson, Lauren, Straub, Cody, Srivastava, Sucheta, Curtis, Christina, Tibshirani, Rob, Angelo, Robert Michael, Hall, Allison, Owzar, Kouros, Polyak, Kornelia, Maley, Carlo, Marks, Jeffrey R., Colditz, Graham A., Hwang, E. Shelley, and West, Robert B.

Published
2023
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21. Validation of the four-miRNA biomarker panel MiCaP for prediction of long-term prostate cancer outcome

Author

Strand, Siri H, Schmidt, Linnéa, Weiss, Simone, Borre, Michael, Kristensen, Helle, Rasmussen, Anne Karin Ildor, Daugaard, Tina Fuglsang, Kristensen, Gitte, Stroomberg, Hein Vincent, Røder, Martin Andreas, Brasso, Klaus, Mouritzen, Peter, Sørensen, Karina Dalsgaard, Strand, Siri H, Schmidt, Linnéa, Weiss, Simone, Borre, Michael, Kristensen, Helle, Rasmussen, Anne Karin Ildor, Daugaard, Tina Fuglsang, Kristensen, Gitte, Stroomberg, Hein Vincent, Røder, Martin Andreas, Brasso, Klaus, Mouritzen, Peter, and Sørensen, Karina Dalsgaard

Abstract

Improved prostate cancer prognostic biomarkers are urgently needed. We previously identified the four-miRNA prognostic biomarker panel MiCaP ((miR-23a-3p × miR-10b-5p)/(miR-133a-3p × miR-374b-5p)) for prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Here, we identified an optimal numerical cut-off for MiCaP dichotomisation using a training cohort of 475 RP patients and tested this in an independent cohort of 281 RP patients (PCA281). Kaplan-Meier, uni- and multivariate Cox regression analyses were conducted for multiple endpoints: BCR, metastatic-(mPC) and castration-resistant prostate cancer (CRPC), prostate cancer-specific (PCSS) and overall survival (OS). Functional effects of the four MiCaP miRNAs were assessed by overexpression and inhibition experiments in prostate cancer cell lines. We found the numerical value 5.709 optimal for MiCaP dichotomisation. This was independently validated in PCA281, where a high MiCaP score significantly [and independent of the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score] predicted BCR, progression to mPC and CRPC, and PCSS, but not OS. Harrell's C-index increased upon addition of MiCaP to CAPRA-S for all endpoints. Inhibition of miR-23a-3p and miR-10b-5p, and overexpression of miR-133a-3p and miR-374b-5p significantly reduced cell survival. Our results may promote future implementation of a MiCaP-based test for improved prostate cancer risk stratification.

Published
2020

22. Abstract PD5-08: The human tumor atlas network (HTAN) breast pre cancer atlas: A multi-omic integrative analysis of ductal carcinoma in situ (DCIS) and correlation with clinical outcomes

Author

Hwang, Shelley, primary, Strand, Siri H, additional, Rivero, Belen, additional, King, Lorraine, additional, Risom, Tyler, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla, additional, Nangia, Julie, additional, Storniolo, Ana Maria, additional, Thompson, Alastair, additional, Gupta, Gaorav, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Burns, Robyn, additional, Zhu, ChunFang, additional, Matusiak, Magda, additional, Zhu, Shirley X, additional, Wang, Jason, additional, Seoane, Jose, additional, Tappenden, Jen, additional, Ding, Daisy, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Vennam, Sujay, additional, Varma, Sushama, additional, Simpson, Lunden, additional, Cisneros, Luis, additional, Hardman, Timmothy, additional, Anderson, Lauren, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Veis, Deb J, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeff, additional, Colditz, Graham, additional, and West, Robert B, additional

Published
2021
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23. Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stroma

Author

Risom, Tyler, primary, Glass, David R, additional, Liu, Candace C, additional, Rivero-Gutiérrez, Belén, additional, Baranski, Alex, additional, McCaffrey, Erin F, additional, Greenwald, Noah F, additional, Kagel, Adam, additional, Strand, Siri H, additional, Varma, Sushama, additional, Kong, Alex, additional, Keren, Leeat, additional, Srivastava, Sucheta, additional, Zhu, Chunfang, additional, Khair, Zumana, additional, Veis, Deborah J, additional, Deschryver, Katherine, additional, Vennam, Sujay, additional, Maley, Carlo, additional, Hwang, E Shelley, additional, Marks, Jefferey R, additional, Bendall, Sean C, additional, Colditz, Graham A, additional, West, Robert B, additional, and Angelo, Michael, additional

Published
2021
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24. The Human Tumor Atlas Network (HTAN) Breast Precancer Atlas: A Multi-Omic Integrative Analysis of Ductal Carcinoma in situ With Clinical Outcomes

Author

Strand, Siri H., primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E., additional, Seoane, Jose A., additional, King, Lorraine, additional, Risom, Tyler, additional, Simpson, Lunden A., additional, Vennam, Sujay, additional, Kahn, Aziz, additional, Cisneros, Luis, additional, Hardman, Timothy, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Rocque, Gabrielle B., additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Ana Maria, additional, Thompson, Alastair, additional, Gupta, Gaorav, additional, Burns, Robyn, additional, Veis, Deborah J., additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X., additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Anderson, Lauren, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R., additional, Colditz, Graham A., additional, Hwang, E. Shelley, additional, and West, Robert B., additional

Published
2021
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25. FRMD6 has tumor suppressor functions in prostate cancer

Author

Haldrup, Jakob, primary, Strand, Siri H., additional, Cieza-Borrella, Clara, additional, Jakobsson, Magnus E., additional, Riedel, Maria, additional, Norgaard, Maibritt, additional, Hedensted, Stine, additional, Dagnaes-Hansen, Frederik, additional, Ulhoi, Benedicte Parm, additional, Eeles, Rosalind, additional, Borre, Michael, additional, Olsen, Jesper V., additional, Thomsen, Martin, additional, Kote-Jarai, Zsofia, additional, and Sorensen, Karina D., additional

Published
2020
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26. Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential

Author

Bjerre, Marianne Trier, primary, Nørgaard, Maibritt, additional, Larsen, Ole Halfdan, additional, Jensen, Sarah Østrup, additional, Strand, Siri H., additional, Østergren, Peter, additional, Fode, Mikkel, additional, Fredsøe, Jacob, additional, Ulhøi, Benedicte Parm, additional, Mortensen, Martin Mørck, additional, Jensen, Jørgen Bjerggaard, additional, Borre, Michael, additional, and Sørensen, Karina D., additional

Published
2020
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27. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Rozenblatt-Rosen, Orit, primary, Regev, Aviv, additional, Oberdoerffer, Philipp, additional, Nawy, Tal, additional, Hupalowska, Anna, additional, Rood, Jennifer E., additional, Ashenberg, Orr, additional, Cerami, Ethan, additional, Coffey, Robert J., additional, Demir, Emek, additional, Ding, Li, additional, Esplin, Edward D., additional, Ford, James M., additional, Goecks, Jeremy, additional, Ghosh, Sharmistha, additional, Gray, Joe W., additional, Guinney, Justin, additional, Hanlon, Sean E., additional, Hughes, Shannon K., additional, Hwang, E. Shelley, additional, Iacobuzio-Donahue, Christine A., additional, Jané-Valbuena, Judit, additional, Johnson, Bruce E., additional, Lau, Ken S., additional, Lively, Tracy, additional, Mazzilli, Sarah A., additional, Pe’er, Dana, additional, Santagata, Sandro, additional, Shalek, Alex K., additional, Schapiro, Denis, additional, Snyder, Michael P., additional, Sorger, Peter K., additional, Spira, Avrum E., additional, Srivastava, Sudhir, additional, Tan, Kai, additional, West, Robert B., additional, Williams, Elizabeth H., additional, Aberle, Denise, additional, Achilefu, Samuel I., additional, Ademuyiwa, Foluso O., additional, Adey, Andrew C., additional, Aft, Rebecca L., additional, Agarwal, Rachana, additional, Aguilar, Ruben A., additional, Alikarami, Fatemeh, additional, Allaj, Viola, additional, Amos, Christopher, additional, Anders, Robert A., additional, Angelo, Michael R., additional, Anton, Kristen, additional, Aster, Jon C., additional, Babur, Ozgun, additional, Bahmani, Amir, additional, Balsubramani, Akshay, additional, Barrett, David, additional, Beane, Jennifer, additional, Bender, Diane E., additional, Bernt, Kathrin, additional, Berry, Lynne, additional, Betts, Courtney B., additional, Bletz, Julie, additional, Blise, Katie, additional, Boire, Adrienne, additional, Boland, Genevieve, additional, Borowsky, Alexander, additional, Bosse, Kristopher, additional, Bott, Matthew, additional, Boyden, Ed, additional, Brooks, James, additional, Bueno, Raphael, additional, Burlingame, Erik A., additional, Cai, Qiuyin, additional, Campbell, Joshua, additional, Caravan, Wagma, additional, Chaib, Hassan, additional, Chan, Joseph M., additional, Chang, Young Hwan, additional, Chatterjee, Deyali, additional, Chaudhary, Ojasvi, additional, Chen, Alyce A., additional, Chen, Bob, additional, Chen, Changya, additional, Chen, Chia-hui, additional, Chen, Feng, additional, Chen, Yu-An, additional, Chheda, Milan G., additional, Chin, Koei, additional, Chiu, Roxanne, additional, Chu, Shih-Kai, additional, Chuaqui, Rodrigo, additional, Chun, Jaeyoung, additional, Cisneros, Luis, additional, Colditz, Graham A., additional, Cole, Kristina, additional, Collins, Natalie, additional, Contrepois, Kevin, additional, Coussens, Lisa M., additional, Creason, Allison L., additional, Crichton, Daniel, additional, Curtis, Christina, additional, Davidsen, Tanja, additional, Davies, Sherri R., additional, de Bruijn, Ino, additional, Dellostritto, Laura, additional, De Marzo, Angelo, additional, DeNardo, David G., additional, Diep, Dinh, additional, Diskin, Sharon, additional, Doan, Xengie, additional, Drewes, Julia, additional, Dubinett, Stephen, additional, Dyer, Michael, additional, Egger, Jacklynn, additional, Eng, Jennifer, additional, Engelhardt, Barbara, additional, Erwin, Graham, additional, Esserman, Laura, additional, Felmeister, Alex, additional, Feiler, Heidi S., additional, Fields, Ryan C., additional, Fisher, Stephen, additional, Flaherty, Keith, additional, Flournoy, Jennifer, additional, Fortunato, Angelo, additional, Frangieh, Allison, additional, Frye, Jennifer L., additional, Fulton, Robert S., additional, Galipeau, Danielle, additional, Gan, Siting, additional, Gao, Jianjiong, additional, Gao, Long, additional, Gao, Peng, additional, Gao, Vianne R., additional, Geiger, Tim, additional, George, Ajit, additional, Getz, Gad, additional, Giannakis, Marios, additional, Gibbs, David L., additional, Gillanders, William E., additional, Goedegebuure, Simon P., additional, Gould, Alanna, additional, Gowers, Kate, additional, Greenleaf, William, additional, Gresham, Jeremy, additional, Guerriero, Jennifer L., additional, Guha, Tuhin K., additional, Guimaraes, Alexander R., additional, Gutman, David, additional, Hacohen, Nir, additional, Hanlon, Sean, additional, Hansen, Casey R., additional, Harismendy, Olivier, additional, Harris, Kathleen A., additional, Hata, Aaron, additional, Hayashi, Akimasa, additional, Heiser, Cody, additional, Helvie, Karla, additional, Herndon, John M., additional, Hirst, Gilliam, additional, Hodi, Frank, additional, Hollmann, Travis, additional, Horning, Aaron, additional, Hsieh, James J., additional, Hughes, Shannon, additional, Huh, Won Jae, additional, Hunger, Stephen, additional, Hwang, Shelley E., additional, Ijaz, Heba, additional, Izar, Benjamin, additional, Jacobson, Connor A., additional, Janes, Samuel, additional, Jayasinghe, Reyka G., additional, Jiang, Lihua, additional, Johnson, Brett E., additional, Johnson, Bruce, additional, Ju, Tao, additional, Kadara, Humam, additional, Kaestner, Klaus, additional, Kagan, Jacob, additional, Kalinke, Lukas, additional, Keith, Robert, additional, Khan, Aziz, additional, Kibbe, Warren, additional, Kim, Albert H., additional, Kim, Erika, additional, Kim, Junhyong, additional, Kolodzie, Annette, additional, Kopytra, Mateusz, additional, Kotler, Eran, additional, Krueger, Robert, additional, Krysan, Kostyantyn, additional, Kundaje, Anshul, additional, Ladabaum, Uri, additional, Lake, Blue B., additional, Lam, Huy, additional, Laquindanum, Rozelle, additional, Laughney, Ashley M., additional, Lee, Hayan, additional, Lenburg, Marc, additional, Leonard, Carina, additional, Leshchiner, Ignaty, additional, Levy, Rochelle, additional, Li, Jerry, additional, Lian, Christine G., additional, Lim, Kian-Huat, additional, Lin, Jia-Ren, additional, Lin, Yiyun, additional, Liu, Qi, additional, Liu, Ruiyang, additional, Longabaugh, William J.R., additional, Longacre, Teri, additional, Ma, Cynthia X., additional, Macedonia, Mary Catherine, additional, Madison, Tyler, additional, Maher, Christopher A., additional, Maitra, Anirban, additional, Makinen, Netta, additional, Makowski, Danika, additional, Maley, Carlo, additional, Maliga, Zoltan, additional, Mallo, Diego, additional, Maris, John, additional, Markham, Nick, additional, Marks, Jeffrey, additional, Martinez, Daniel, additional, Mashl, Robert J., additional, Masilionais, Ignas, additional, Mason, Jennifer, additional, Massagué, Joan, additional, Massion, Pierre, additional, Mattar, Marissa, additional, Mazurchuk, Richard, additional, Mazutis, Linas, additional, McKinley, Eliot T., additional, McMichael, Joshua F., additional, Merrick, Daniel, additional, Meyerson, Matthew, additional, Miessner, Julia R., additional, Mills, Gordon B., additional, Mills, Meredith, additional, Mondal, Suman B., additional, Mori, Motomi, additional, Mori, Yuriko, additional, Moses, Elizabeth, additional, Mosse, Yael, additional, Muhlich, Jeremy L., additional, Murphy, George F., additional, Navin, Nicholas E., additional, Nederlof, Michel, additional, Ness, Reid, additional, Nevins, Stephanie, additional, Nikolov, Milen, additional, Nirmal, Ajit Johnson, additional, Nolan, Garry, additional, Novikov, Edward, additional, O’Connell, Brendan, additional, Offin, Michael, additional, Oh, Stephen T., additional, Olson, Anastasiya, additional, Ooms, Alex, additional, Ossandon, Miguel, additional, Owzar, Kouros, additional, Parmar, Swapnil, additional, Patel, Tasleema, additional, Patti, Gary J., additional, Pe'er, Itsik, additional, Peng, Tao, additional, Persson, Daniel, additional, Petty, Marvin, additional, Pfister, Hanspeter, additional, Polyak, Kornelia, additional, Pourfarhangi, Kamyar, additional, Puram, Sidharth V., additional, Qiu, Qi, additional, Quintanal-Villalonga, Álvaro, additional, Raj, Arjun, additional, Ramirez-Solano, Marisol, additional, Rashid, Rumana, additional, Reeb, Ashley N., additional, Reid, Mary, additional, Resnick, Adam, additional, Reynolds, Sheila M., additional, Riesterer, Jessica L., additional, Rodig, Scott, additional, Roland, Joseph T., additional, Rosenfield, Sonia, additional, Rotem, Asaf, additional, Roy, Sudipta, additional, Rozenblatt-Rosen, Orit, additional, Rudin, Charles M., additional, Ryser, Marc D., additional, Santi-Vicini, Maria, additional, Sato, Kazuhito, additional, Schrag, Deborah, additional, Schultz, Nikolaus, additional, Sears, Cynthia L., additional, Sears, Rosalie C., additional, Sen, Subrata, additional, Sen, Triparna, additional, Shalek, Alex, additional, Sheng, Jeff, additional, Sheng, Quanhu, additional, Shoghi, Kooresh I., additional, Shrubsole, Martha J., additional, Shyr, Yu, additional, Sibley, Alexander B., additional, Siex, Kiara, additional, Simmons, Alan J., additional, Singer, Dinah S., additional, Sivagnanam, Shamilene, additional, Slyper, Michal, additional, Sokolov, Artem, additional, Song, Sheng-Kwei, additional, Southard-Smith, Austin, additional, Spira, Avrum, additional, Stein, Janet, additional, Storm, Phillip, additional, Stover, Elizabeth, additional, Strand, Siri H., additional, Su, Timothy, additional, Sudar, Damir, additional, Sullivan, Ryan, additional, Surrey, Lea, additional, Suvà, Mario, additional, Terekhanova, Nadezhda V., additional, Ternes, Luke, additional, Thammavong, Lisa, additional, Thibault, Guillaume, additional, Thomas, George V., additional, Thorsson, Vésteinn, additional, Todres, Ellen, additional, Tran, Linh, additional, Tyler, Madison, additional, Uzun, Yasin, additional, Vachani, Anil, additional, Van Allen, Eliezer, additional, Vandekar, Simon, additional, Veis, Deborah J., additional, Vigneau, Sébastien, additional, Vossough, Arastoo, additional, Waanders, Angela, additional, Wagle, Nikhil, additional, Wang, Liang-Bo, additional, Wendl, Michael C., additional, West, Robert, additional, Wu, Chi-yun, additional, Wu, Hao, additional, Wu, Hung-Yi, additional, Wyczalkowski, Matthew A., additional, Xie, Yubin, additional, Yang, Xiaolu, additional, Yapp, Clarence, additional, Yu, Wenbao, additional, Yuan, Yinyin, additional, Zhang, Dadong, additional, Zhang, Kun, additional, Zhang, Mianlei, additional, Zhang, Nancy, additional, Zhang, Yantian, additional, Zhao, Yanyan, additional, Zhou, Daniel Cui, additional, Zhou, Zilu, additional, Zhu, Houxiang, additional, Zhu, Qin, additional, Zhu, Xiangzhu, additional, Zhu, Yuankun, additional, and Zhuang, Xiaowei, additional

Published
2020
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28. Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells

Author

Laursen, Emma B, Fredsøe, Jacob, Schmidt, Linnéa, Strand, Siri H, Kristensen, Helle, Rasmussen, Anne K I, Daugaard, Tina F, Mouritzen, Peter, Høyer, Søren, Kristensen, Gitte, Stroomberg, Hein V, Brasso, Klaus, Røder, Martin Andreas, Borre, Michael, Sørensen, Karina D, Laursen, Emma B, Fredsøe, Jacob, Schmidt, Linnéa, Strand, Siri H, Kristensen, Helle, Rasmussen, Anne K I, Daugaard, Tina F, Mouritzen, Peter, Høyer, Søren, Kristensen, Gitte, Stroomberg, Hein V, Brasso, Klaus, Røder, Martin Andreas, Borre, Michael, and Sørensen, Karina D

Abstract

miR-615-3p has previously been described as up-regulated in prostate cancer (PC) tissue samples compared with nonmalignant controls; however, its prognostic potential and functional role in PC remain largely unknown. In this study, we investigated the clinical and biological relevance of miR-615-3p in PC. The expression of miR-615-3p was measured in PC tissue specimens from 239 men who underwent radical prostatectomy (RP), and it was investigated if miR-615-3p could predict postoperative biochemical recurrence (BCR). These findings were subsequently validated in three independent RP cohorts (n = 222, n = 273, and n = 387) and functional overexpression studies conducted in PC cells (PC3M). High miR-615-3p expression was significantly associated with BCR in four independent PC patient cohorts (P < 0.05, log-rank test). In addition, high miR-615-3p expression was a significant predictor of PC-specific survival in univariate (hazard ratio, 3.75; P < 0.001) and multivariate (hazard ratio, 2.66; P = 0.008) analysis after adjustment for the Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) nomogram in a merged RP cohort (n = 734). Moreover, overexpression of miR-615-3p in PC cells (PC3M) significantly increased cell viability, proliferation, apoptosis, and migration. Together, our results suggest that miR-615-3p is a significant predictor of postoperative BCR and PC-specific survival and has oncogenic functions in PC cells.

Published
2019

29. 5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

Author

Kristensen, Gitte, Strand, Siri H, Røder, Martin Andreas, Berg, Kasper Drimer, Toft, Birgitte Grønkær, Høyer, Søren, Borre, Michael, Sørensen, Karina Dalsgaard, Brasso, Klaus, Kristensen, Gitte, Strand, Siri H, Røder, Martin Andreas, Berg, Kasper Drimer, Toft, Birgitte Grønkær, Høyer, Søren, Borre, Michael, Sørensen, Karina Dalsgaard, and Brasso, Klaus

Abstract

This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5⁻10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2⁻2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.

Published
2019

33. RHCG and TCAF1 promoter hypermethylation predicts biochemical recurrence in prostate cancer patients treated by radical prostatectomy

Author

Strand, Siri H, Switnicki, Michal, Moller, Mia, Haldrup, Christa, Storebjerg, Tine M, Hedegaard, Jakob, Nordentoft, Iver, Hoyer, Soren, Borre, Michael, Pedersen, Jakob S, Wild, Peter J; https://orcid.org/0000-0002-1017-3744, Park, Jong Y, Orntoft, Torben F, Sorensen, Karina D, Strand, Siri H, Switnicki, Michal, Moller, Mia, Haldrup, Christa, Storebjerg, Tine M, Hedegaard, Jakob, Nordentoft, Iver, Hoyer, Soren, Borre, Michael, Pedersen, Jakob S, Wild, Peter J; https://orcid.org/0000-0002-1017-3744, Park, Jong Y, Orntoft, Torben F, and Sorensen, Karina D

Abstract

PURPOSE: The lack of biomarkers that can distinguish aggressive from indolent prostate cancer has caused substantial overtreatment of clinically insignificant disease. Here, by genome-wide DNA methylome profiling, we sought to identify new biomarkers to improve the accuracy of prostate cancer diagnosis and prognosis. EXPERIMENTAL DESIGN: Eight novel candidate markers, COL4A6, CYBA, TCAF1 (FAM115A), HLF, LINC01341 (LOC149134), LRRC4, PROM1, and RHCG, were selected from Illumina Infinium HumanMethylation450 BeadChip analysis of 21 tumor (T) and 21 non-malignant (NM) prostate specimens. Diagnostic potential was further investigated by methylation-specific qPCR analysis of 80 NM vs. 228 T tissue samples. Prognostic potential was assessed by Kaplan-Meier, uni- and multivariate Cox regression analysis in 203 Danish radical prostatectomy (RP) patients (cohort 1), and validated in an independent cohort of 286 RP patients from Switzerland and the U.S. (cohort 2). RESULTS: Hypermethylation of the 8 candidates was highly cancer-specific (area under the curves: 0.79-1.00). Furthermore, high methylation of the 2-gene panel RHCG-TCAF1 was predictive of biochemical recurrence (BCR) in cohort 1, independent of the established clinicopathological parameters Gleason score, pathological tumor stage, and pre-operative PSA (HR (95% confidence interval (CI)): 2.09 (1.26 - 3.46); P = 0.004), and this was successfully validated in cohort 2 (HR (95% CI): 1.81 (1.05 - 3.12); P = 0.032). CONCLUSION: Methylation of the RHCG-TCAF1 panel adds significant independent prognostic value to established prognostic parameters for prostate cancer and thus may help to guide treatment decisions in the future. Further investigation in large independent cohorts is necessary before translation into clinical utility.

Published
2017

34. FRMD6has tumor suppressor functions in prostate cancer

Author

Haldrup, Jakob, Strand, Siri H., Cieza-Borrella, Clara, Jakobsson, Magnus E., Riedel, Maria, Norgaard, Maibritt, Hedensted, Stine, Dagnaes-Hansen, Frederik, Ulhoi, Benedicte Parm, Eeles, Rosalind, Borre, Michael, Olsen, Jesper V., Thomsen, Martin, Kote-Jarai, Zsofia, and Sorensen, Karina D.

Abstract

Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6(FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6deficient PC cells. Finally, we established orthotropic Frmd6and Pten, or Ptenonly (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Ptendouble knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Ptensingle-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.

Published
2021
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35. RHCG and TCAF1 promoter hypermethylation predicts biochemical recurrence in prostate cancer patients treated by radical prostatectomy

Author

Strand, Siri H., primary, Switnicki, Michal, additional, Moller, Mia, additional, Haldrup, Christa, additional, Storebjerg, Tine M., additional, Hedegaard, Jakob, additional, Nordentoft, Iver, additional, Hoyer, Soren, additional, Borre, Michael, additional, Pedersen, Jakob S., additional, Wild, Peter J., additional, Park, Jong Y., additional, Orntoft, Torben F., additional, and Sorensen, Karina D., additional

Published
2016
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36. HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer

Author

Ross-Adams, Helen, primary, Ball, Stephen, additional, Lawrenson, Kate, additional, Halim, Silvia, additional, Russell, Roslin, additional, Wells, Claire, additional, Strand, Siri H., additional, Ørntoft, Torben F., additional, Larson, Melissa, additional, Armasu, Sebastian, additional, Massie, Charles E., additional, Asim, Mohammad, additional, Mortensen, Martin M., additional, Borre, Michael, additional, Woodfine, Kathryn, additional, Warren, Anne Y., additional, Lamb, Alastair D., additional, Kay, Jonathan, additional, Whitaker, Hayley, additional, Ramos-Montoya, Antonio, additional, Murrell, Adele, additional, Sørensen, Karina D., additional, Fridley, Brooke L., additional, Goode, Ellen L., additional, Gayther, Simon A., additional, Masters, John, additional, Neal, David E., additional, and Mills, Ian G., additional

Published
2016
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38. Biomarker potential of <italic>ST6GALNAC3</italic> and <italic>ZNF660</italic> promoter hypermethylation in prostate cancer tissue and liquid biopsies.

Author

Haldrup, Christa, Pedersen, Anne L., Øgaard, Nadia, Strand, Siri H., Høyer, Søren, Borre, Michael, Ørntoft, Torben F., and Sørensen, Karina D.

Abstract

Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of specific genes has been suggested as novel candidate biomarkers for PC that may improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter methylation in prostate tissues, and ST6GALNAC3, ZNF660, CCDC181, and HAPLN3 promoter methylation in liquid biopsies. First, using four independent patient sample sets, including a total of 110 nonmalignant (NM) and 705 PC tissue samples, analyzed by methylation‐specific qPCR or methylation array, we found that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer‐specific with areas under the curve (AUC) of receiver operating characteristic (ROC) curve analysis of 0.917–0.995 and 0.846–0.903, respectively. Furthermore, ZNF660 hypermethylation was significantly associated with biochemical recurrence in two radical prostatectomy (RP) cohorts of 158 and 392 patients and remained significant also in the subsets of patients with Gleason score ≤7 (univariate Cox regression and log‐rank tests, P < 0.05), suggesting that ZNF660 methylation analysis can potentially help to stratify low‐/intermediate‐grade PCs into indolent vs. more aggressive subtypes. Notably, ZNF660 hypermethylation was also significantly associated with poor overall and PC‐specific survival in the RP cohort (n = 158) with long clinical follow‐up available. Moreover, as proof of principle, we successfully detected highly PC‐specific hypermethylated circulating tumor DNA (ctDNA) for ST6GALNAC3, ZNF660, HAPLN3, and CCDC181 in liquid biopsies (serum) from 27 patients with PC vs. 10 patients with BPH, using droplet digital methylation‐specific PCR analysis. Finally, we generated a three‐gene (ST6GALNAC3/CCDC181/HAPLN3) ctDNA hypermethylation model, which detected PC with 100% specificity and 67% sensitivity. In conclusion, we here for the first time demonstrate diagnostic biomarker potential of ST6GALNAC3 and ZNF660 methylation, as well as prognostic biomarker potential of ZNF660. Furthermore, we show that hypermethylation of four genes can be detected in ctDNA in liquid biopsies (serum) from patients with PC. [ABSTRACT FROM AUTHOR]

Published
2018
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41. From the lab to the clinic: Lessons learned from a translational working group.

Author

Lynch, Thomas, Basila, Desiree, Schnitt, Stuart J., Marks, Jeffrey R, Strand, Siri H, Hyslop, Terry, Badve, Sunil S., Watson, Mark A, Le-Petross, Huong T., Grimm, Lars, West, Robert B., Weiss, Anna, Rapperport, Anna, King, Lorraine, Factor, Rachel E., Ryser, Marc D, Partridge, Ann H., Hwang, Eun-Sil Shelley, Thompson, Alastair Mark, and Collyar, Deborah E.

Published
2023
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43. Aberrant DOCK2, GRASP, HIF3A and PKFP Hypermethylation has Potential as a Prognostic Biomarker for Prostate Cancer.

Author

Bjerre, Marianne T., Strand, Siri H., Nørgaard, Maibritt, Kristensen, Helle, Rasmussen, Anne KI, Mortensen, Martin Mørck, Fredsøe, Jacob, Mouritzen, Peter, Ulhøi, Benedicte, Ørntoft, Torben, Borre, Michael, and Sørensen, Karina D.

Subjects
*PROSTATE cancer, *BIOLOGICAL tags, *DNA, *CONFIDENCE intervals, *GENE expression
Abstract

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75–94%) and specificity (84–100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24–3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also. [ABSTRACT FROM AUTHOR]

Published
2019
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44. Single Cell Expression Analysis of Ductal Carcinoma in Situ Identifies Complex Genotypic-Phenotypic Relationships Altering Epithelial Composition.

Author

Qin X, Strand SH, Lee MR, Saraswathibhatla A, van IJzendoorn DGP, Zhu C, Vennam S, Varma S, Hall A, Factor RE, King L, Simpson L, Luo X, Colditz GA, Jiang S, Chaudhuri O, Hwang ES, Marks JR, Owzar K, and West RB

Abstract

To identify mechanisms underlying the growth of ductal carcinoma in situ (DCIS) and properties that lead to progression to invasive cancer, we performed single-cell RNA-sequencing (scRNA-seq) on DCIS lesions and matched synchronous normal breast tissue. Using inferred copy number variations (CNV), we identified neoplastic epithelial cells from the clinical specimens which contained a mixture of DCIS and normal ducts. Phylogenetic analysis based on the CNVs demonstrated intratumoral clonal heterogeneity was associated with significant gene expression differences. We also classified epithelial cells into mammary cell states and found that individual genetic clones contained a mixture of cell states suggesting an ongoing pattern of differentiation after neoplastic transformation. Cell state proportions were significantly different based on estrogen receptor (ER) expression with ER-DCIS more closely resembling the distribution in the normal breast, particularly with respect to cells with basal characteristics. Using deconvolution from bulk RNA-seq in archival DCIS specimens, we show that specific alterations in cell state proportions are associated with progression to invasive cancer. Loss of an intact basement membrane (BM) is the functional definition of invasive breast cancer (IBC) and scRNA-seq data demonstrated that ongoing transcription of key BM genes occurs in specific subsets of epithelial cell states. Examining BM in archival microinvasive breast cancers and an in vitro model of invasion, we found that passive loss of BM gene expression due to cell state proportion alterations is associated with loss of the structural integrity of the duct leading to an invasive phenotype. Our analyses provide detailed insight into DCIS biology., Significance: Single cell analysis reveals that preinvasive breast cancer is comprised of multiple genetic clones and there is substantial phenotypic diversity both within and between these clones. Ductal carcinoma in situ (DCIS) of the breast is a non-invasive condition commonly identified through mammographic screening. A primary diagnosis of DCIS carries little mortality risk on its own, but its presence is a risk factor for subsequent clonally related invasive breast cancer (IBC) (1-5).

Published
2024
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45. 5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors.

Author

Kristensen G, Strand SH, Røder MA, Berg KD, Toft BG, Høyer S, Borre M, Sørensen KD, and Brasso K

Subjects
5-Methylcytosine metabolism, Aged, Cohort Studies, Humans, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, ROC Curve, Transcriptional Regulator ERG metabolism, 5-Methylcytosine analogs & derivatives, Prostatectomy, Prostatic Neoplasms metabolism, Prostatic Neoplasms surgery
Abstract

This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5⁻10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF ( p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP ( p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2⁻2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.

Published
2019
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46. RHCG and TCAF1 promoter hypermethylation predicts biochemical recurrence in prostate cancer patients treated by radical prostatectomy.

Author

Strand SH, Switnicki M, Moller M, Haldrup C, Storebjerg TM, Hedegaard J, Nordentoft I, Hoyer S, Borre M, Pedersen JS, Wild PJ, Park JY, Orntoft TF, and Sorensen KD

Subjects
Adult, Aged, Denmark, Epigenesis, Genetic, Humans, Male, Middle Aged, Neoplasm Grading, Prognosis, Promoter Regions, Genetic, Prostatectomy, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Survival Analysis, Switzerland, United States, Biomarkers, Tumor genetics, Cation Transport Proteins genetics, DNA Methylation, Membrane Glycoproteins genetics, Membrane Proteins genetics, Prostatic Neoplasms surgery
Abstract

Purpose: The lack of biomarkers that can distinguish aggressive from indolent prostate cancer has caused substantial overtreatment of clinically insignificant disease. Here, by genome-wide DNA methylome profiling, we sought to identify new biomarkers to improve the accuracy of prostate cancer diagnosis and prognosis., Experimental Design: Eight novel candidate markers, COL4A6, CYBA, TCAF1 (FAM115A), HLF, LINC01341 (LOC149134), LRRC4, PROM1, and RHCG, were selected from Illumina Infinium HumanMethylation450 BeadChip analysis of 21 tumor (T) and 21 non-malignant (NM) prostate specimens. Diagnostic potential was further investigated by methylation-specific qPCR analysis of 80 NM vs. 228 T tissue samples. Prognostic potential was assessed by Kaplan-Meier, uni- and multivariate Cox regression analysis in 203 Danish radical prostatectomy (RP) patients (cohort 1), and validated in an independent cohort of 286 RP patients from Switzerland and the U.S. (cohort 2)., Results: Hypermethylation of the 8 candidates was highly cancer-specific (area under the curves: 0.79-1.00). Furthermore, high methylation of the 2-gene panel RHCG-TCAF1 was predictive of biochemical recurrence (BCR) in cohort 1, independent of the established clinicopathological parameters Gleason score, pathological tumor stage, and pre-operative PSA (HR (95% confidence interval (CI)): 2.09 (1.26 - 3.46); P = 0.004), and this was successfully validated in cohort 2 (HR (95% CI): 1.81 (1.05 - 3.12); P = 0.032)., Conclusion: Methylation of the RHCG-TCAF1 panel adds significant independent prognostic value to established prognostic parameters for prostate cancer and thus may help to guide treatment decisions in the future. Further investigation in large independent cohorts is necessary before translation into clinical utility.

Published
2017
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47. Prognostic DNA methylation markers for prostate cancer.

Author

Strand SH, Orntoft TF, and Sorensen KD

Subjects
Adenocarcinoma chemistry, Adenocarcinoma mortality, Biomarkers, Body Fluids chemistry, DNA, Neoplasm analysis, DNA, Neoplasm chemistry, Early Detection of Cancer, Gene Expression Profiling, Humans, Male, MicroRNAs genetics, Microtubule Proteins, Neoplasm Invasiveness genetics, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic genetics, Prostatic Neoplasms chemistry, Prostatic Neoplasms mortality, Proteins genetics, Adenocarcinoma genetics, DNA Methylation, DNA, Neoplasm genetics, Gene Expression Regulation, Neoplastic physiology, Neoplasm Proteins genetics, Prostatic Neoplasms genetics, RNA, Neoplasm genetics
Abstract

Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

Published
2014
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