Search

Your search keyword '"Ogino Shuji"' showing total 2,828 results
Start Over Author "Ogino Shuji"
2,828 results on '"Ogino Shuji"'

2. A pathology foundation model for cancer diagnosis and prognosis prediction

Author

Wang, Xiyue, Zhao, Junhan, Marostica, Eliana, Yuan, Wei, Jin, Jietian, Zhang, Jiayu, Li, Ruijiang, Tang, Hongping, Wang, Kanran, Li, Yu, Wang, Fang, Peng, Yulong, Zhu, Junyou, Zhang, Jing, Jackson, Christopher R., Zhang, Jun, Dillon, Deborah, Lin, Nancy U., Sholl, Lynette, Denize, Thomas, Meredith, David, Ligon, Keith L., Signoretti, Sabina, Ogino, Shuji, Golden, Jeffrey A., Nasrallah, MacLean P., Han, Xiao, Yang, Sen, and Yu, Kun-Hsing

Published
2024
Full Text
View/download PDF

3. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author

Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei

Published
2024
Full Text
View/download PDF

4. Germline genetic regulation of the colorectal tumor immune microenvironment

Author

Schmit, Stephanie L., Tsai, Ya-Yu, Bonner, Joseph D., Sanz-Pamplona, Rebeca, Joshi, Amit D., Ugai, Tomotaka, Lindsey, Sidney S., Melas, Marilena, McDonnell, Kevin J., Idos, Gregory E., Walker, Christopher P., Qu, Chenxu, Kast, W. Martin, Da Silva, Diane M., Glickman, Jonathan N., Chan, Andrew T., Giannakis, Marios, Nowak, Jonathan A., Rennert, Hedy S., Robins, Harlan S., Ogino, Shuji, Greenson, Joel K., Moreno, Victor, Rennert, Gad, and Gruber, Stephen B.

Published
2024
Full Text
View/download PDF

5. Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk

Author

Tian, Yu, Lin, Yi, Qu, Conghui, Arndt, Volker, Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Buchanan, Daniel D., Budiarto, Arif, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Chan, Andrew T., Chen, Rui, Chen, Xuechen, Conti, David V., Díez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Gallinger, Steven, Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harlid, Sophia, Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Jenkins, Mark A., Jordahl, Kristina M., Joshi, Amit D., Keku, Temitope O., Kawaguchi, Eric, Kim, Andre E., Kundaje, Anshul, Larsson, Susanna C., Marchand, Loic Le, Lewinger, Juan Pablo, Li, Li, Moreno, Victor, Morrison, John, Murphy, Neil, Nan, Hongmei, Nassir, Rami, Newcomb, Polly A., Obón-Santacana, Mireia, Ogino, Shuji, Ose, Jennifer, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Prentice, Ross L., Rennert, Gad, Ruiz-Narvaez, Edward A., Sakoda, Lori C., Schoen, Robert E., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Thibodeau, Stephen N., Thomas, Duncan C., Tsilidis, Konstantinos K., van Duijnhoven, Franzel J. B., Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Peters, Ulrike, Gauderman, W. James, Hsu, Li, and Chang-Claude, Jenny

Published
2024
Full Text
View/download PDF

6. Allometric versus traditional body-shape indices and risk of colorectal cancer: a Mendelian randomization analysis

Author

Rontogianni, Marina O., Bouras, Emmanouil, Aglago, Elom Kouassivi, Freisling, Heinz, Murphy, Neil, Cotterchio, Michelle, Hampe, Jochen, Lindblom, Annika, Pai, Rish K., Pharoah, Paul D. P., Phipps, Amanda I., van Duijnhoven, Franzel J. B., Visvanathan, Kala, van Guelpen, Bethany, Li, Christopher I., Brenner, Hermann, Pellatt, Andrew J., Ogino, Shuji, Gunter, Marc J., Peters, Ulrike, Christakoudi, Sofia, and Tsilidis, Konstantinos K.

Published
2024
Full Text
View/download PDF

7. Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic

Author

USERN Advisory Board, Yazdanpanah, Niloufar, Sedikides, Constantine, Ochs, Hans D., Camargo, Carlos A., Jr., Darmstadt, Gary L., Cerda, Artemi, Cauda, Valentina, Peters, Godefridus J., Sellke, Frank, Wong, Nathan D., Comini, Elisabetta, Jimeno, Alberto Ruiz, Glover, Vivette, Hatziargyriou, Nikos, Vincenot, Christian E., Bordas, Stéphane P. A., Rao, Idupulapati M., Abolhassani, Hassan, Gharehpetian, Gevork B., Weiskirchen, Ralf, Gupta, Manoj, Chandel, Shyam Singh, Olusanya, Bolajoko O., Cheson, Bruce, Pomponio, Alessio, Tanzer, Michael, Myles, Paul S., Ma, Wen-Xiu, Bella, Federico, Ghavami, Saeid, Moein Moghimi, S., Pratico, Domenico, Hernandez, Alfredo M., Martinez-Urbistondo, Maria, Urbistondo, Diego Martinez, Fereshtehnejad, Seyed-Mohammad, Ali, Imran, Kimura, Shinya, Wallace Hayes, A., Cai, Wenju, Ernest, Chua K. J., Thomas, Sabu, Rahimi, Kazem, Sorooshian, Armin, Schreiber, Michael, Kato, Koichi, Luong, John H. T., Pluchino, Stefano, Lozano, Andres M., Seymour, John F., Kosik, Kenneth S., Hofmann, Stefan G., McIntyre, Roger S., Perc, Matjaz, Leemans, Alexander, Klein, Robyn S., Ogino, Shuji, Wlezien, Christopher, Perry, George, Nieto, Juan J., Levin, Lisa, Klionsky, Daniel J., Mobasher, Bahram, Dorigo, Tommaso, Rezaei, Nima, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, and Rosenhouse-Dantsker, Avia, Editorial Board Member

Published
2024
Full Text
View/download PDF

8. The Subtype-Free Average Causal Effect for Heterogeneous Disease Etiology

Author

Sasson, Amit, Wang, Molin, Ogino, Shuji, and Nevo, Daniel

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Studies have shown that the effect an exposure may have on a disease can vary for different subtypes of the same disease. However, existing approaches to estimate and compare these effects largely overlook causality. In this paper, we study the effect smoking may have on having colorectal cancer subtypes defined by a trait known as microsatellite instability (MSI). We use principal stratification to propose an alternative causal estimand, the Subtype-Free Average Causal Effect (SF-ACE). The SF-ACE is the causal effect of the exposure among those who would be free from other disease subtypes under any exposure level. We study non-parametric identification of the SF-ACE, and discuss different monotonicity assumptions, which are more nuanced than in the standard setting. As is often the case with principal stratum effects, the assumptions underlying the identification of the SF-ACE from the data are untestable and can be too strong. Therefore, we also develop sensitivity analysis methods that relax these assumptions. We present three different estimators, including a doubly-robust estimator, for the SF-ACE. We implement our methodology for data from two large cohorts to study the heterogeneity in the causal effect of smoking on colorectal cancer with respect to MSI subtypes.

Published
2022

9. An Empirical Dietary Pattern Associated With the Gut Microbial Features in Relation to Colorectal Cancer Risk

Author

Wang, Kai, Lo, Chun-Han, Mehta, Raaj S., Nguyen, Long H., Wang, Yiqing, Ma, Wenjie, Ugai, Tomotaka, Kawamura, Hidetaka, Ugai, Satoko, Takashima, Yasutoshi, Mima, Kosuke, Arima, Kota, Okadome, Kazuo, Giannakis, Marios, Sears, Cynthia L., Meyerhardt, Jeffrey A., Ng, Kimmie, Segata, Nicola, Izard, Jacques, Rimm, Eric B., Garrett, Wendy S., Huttenhower, Curtis, Giovannucci, Edward L., Chan, Andrew T., Ogino, Shuji, and Song, Mingyang

Published
2024
Full Text
View/download PDF

10. Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.

Author

Tian, Yu, Kim, Andre E, Bien, Stephanie A, Lin, Yi, Qu, Conghui, Harrison, Tabitha A, Carreras-Torres, Robert, Díez-Obrero, Virginia, Dimou, Niki, Drew, David A, Hidaka, Akihisa, Huyghe, Jeroen R, Jordahl, Kristina M, Morrison, John, Murphy, Neil, Obón-Santacana, Mireia, Ulrich, Cornelia M, Ose, Jennifer, Peoples, Anita R, Ruiz-Narvaez, Edward A, Shcherbina, Anna, Stern, Mariana C, Su, Yu-Ru, van Duijnhoven, Franzel JB, Arndt, Volker, Baurley, James W, Berndt, Sonja I, Bishop, D Timothy, Brenner, Hermann, Buchanan, Daniel D, Chan, Andrew T, Figueiredo, Jane C, Gallinger, Steven, Gruber, Stephen B, Harlid, Sophia, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Larsson, Susanna C, Le Marchand, Loic, Li, Li, Giles, Graham G, Milne, Roger L, Nan, Hongmei, Nassir, Rami, Ogino, Shuji, Budiarto, Arif, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Rennert, Gad, Sakoda, Lori C, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Van Guelpen, Bethany, Visvanathan, Kala, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Campbell, Peter T, Casey, Graham, Conti, David V, Gunter, Marc J, Kundaje, Anshul, Lewinger, Juan Pablo, Moreno, Victor, Newcomb, Polly A, Pardamean, Bens, Thomas, Duncan C, Tsilidis, Konstantinos K, Peters, Ulrike, Gauderman, W James, Hsu, Li, and Chang-Claude, Jenny

Subjects
Humans, Colorectal Neoplasms, Estrogens, Progestins, Risk Factors, Case-Control Studies, Menopause, Polymorphism, Single Nucleotide, Female, Aging, Digestive Diseases, Estrogen, Colo-Rectal Cancer, Genetics, Prevention, Human Genome, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.MethodsWe conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.ResultsThe use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P

Published
2022

11. Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing

Author

Aglago, Elom K, Qu, Conghui, Harlid, Sophia, Phipps, Amanda I, Steinfelder, Robert S, Ogino, Shuji, Thomas, Claire E, Hsu, Li, Toland, Amanda E, Brenner, Hermann, Berndt, Sonja I, Buchanan, Daniel D, Campbell, Peter T, Cao, Yin, Chan, Andrew T, Drew, David A, Figueiredo, Jane C, French, Amy J, Gallinger, Steven, Georgeson, Peter, Giannakis, Marios, Goode, Ellen L, Gruber, Stephen B, Gunter, Marc J, Harrison, Tabitha A, Hoffmeister, Michael, Huang, Wen-Yi, Hullar, Meredith AJ, Huyghe, Jeroen R, Jenkins, Mark A, Lynch, Brigid M, Moreno, Victor, Murphy, Neil, Newton, Christina C, Nowak, Jonathan A, Obón-Santacana, Mireia, Sun, Wei, Ugai, Tomotaka, Um, Caroline Y, Zaidi, Syed H, Tsilidis, Konstantinos K, van Guelpen, Bethany, and Peters, Ulrike

Published
2024
Full Text
View/download PDF

16. Genome-wide association study identifies tumor anatomical site-specific risk variants for colorectal cancer survival

Author

Labadie, Julia D, Savas, Sevtap, Harrison, Tabitha A, Banbury, Barb, Huang, Yuhan, Buchanan, Daniel D, Campbell, Peter T, Gallinger, Steven J, Giles, Graham G, Gunter, Marc J, Hoffmeister, Michael, Hsu, Li, Jenkins, Mark A, Lin, Yi, Ogino, Shuji, Phipps, Amanda I, Slattery, Martha L, Steinfelder, Robert S, Sun, Wei, Van Guelpen, Bethany, Hua, Xinwei, Figuieredo, Jane C, Pai, Rish K, Nassir, Rami, Qi, Lihong, Chan, Andrew T, Peters, Ulrike, and Newcomb, Polly A

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Colo-Rectal Cancer, Prevention, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Colorectal Neoplasms, Databases, Genetic, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Middle Aged, Neoplasm Staging, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Young Adult
Abstract

Identification of new genetic markers may improve the prediction of colorectal cancer prognosis. Our objective was to examine genome-wide associations of germline genetic variants with disease-specific survival in an analysis of 16,964 cases of colorectal cancer. We analyzed genotype and colorectal cancer-specific survival data from a consortium of 15 studies. Approximately 7.5 million SNPs were examined under the log-additive model using Cox proportional hazards models, adjusting for clinical factors and principal components. Additionally, we ran secondary analyses stratifying by tumor site and disease stage. We used a genome-wide p-value threshold of 5 × 10-8 to assess statistical significance. No variants were statistically significantly associated with disease-specific survival in the full case analysis or in the stage-stratified analyses. Three SNPs were statistically significantly associated with disease-specific survival for cases with tumors located in the distal colon (rs698022, HR = 1.48, CI 1.30-1.69, p = 8.47 × 10-9) and the proximal colon (rs189655236, HR = 2.14, 95% CI 1.65-2.77, p = 9.19 × 10-9 and rs144717887, HR = 2.01, 95% CI 1.57-2.58, p = 3.14 × 10-8), whereas no associations were detected for rectal tumors. Findings from this large genome-wide association study highlight the potential for anatomical-site-stratified genome-wide studies to identify germline genetic risk variants associated with colorectal cancer-specific survival. Larger sample sizes and further replication efforts are needed to more fully interpret these findings.

Published
2022

19. Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop

Author

Bunyavanich, Supinda, Becker, Patrice M., Altman, Matthew C., Lasky-Su, Jessica, Ober, Carole, Zengler, Karsten, Berdyshev, Evgeny, Bonneau, Richard, Chatila, Talal, Chatterjee, Nilanjan, Chung, Kian Fan, Cutcliffe, Colleen, Davidson, Wendy, Dong, Gang, Fang, Gang, Fulkerson, Patricia, Himes, Blanca E., Liang, Liming, Mathias, Rasika A., Ogino, Shuji, Petrosino, Joseph, Price, Nathan D., Schadt, Eric, Schofield, James, Seibold, Max A., Steen, Hanno, Wheatley, Lisa, Zhang, Hongmei, Togias, Alkis, and Hasegawa, Kohei

Published
2024
Full Text
View/download PDF

20. Interindividual immunogenic variants: Susceptibility to coronavirus, respiratory syncytial virus and influenza virus

Author

Darbeheshti, Farzaneh, Mahdiannasser, Mojdeh, Uhal, Bruce D, Ogino, Shuji, Gupta, Sudhir, and Rezaei, Nima

Subjects
Microbiology, Biological Sciences, Genetics, Prevention, Influenza, Immunization, Vaccine Related, Lung, Pneumonia & Influenza, Infectious Diseases, Emerging Infectious Diseases, Biodefense, Aetiology, 2.1 Biological and endogenous factors, Infection, Inflammatory and immune system, Good Health and Well Being, Antiviral Agents, Biological Variation, Individual, COVID-19, Cytokine Release Syndrome, Gene Expression, Genetic Predisposition to Disease, Humans, Immunity, Innate, Immunologic Factors, Influenza, Human, Mannose-Binding Lectin, Orthomyxoviridae, Respiratory Syncytial Virus Infections, Respiratory Syncytial Viruses, Severe acute respiratory syndrome-related coronavirus, SARS-CoV-2, Severe Acute Respiratory Syndrome, Toll-Like Receptors, COVID-19 Drug Treatment, Covid-19, cytokine storm, genetic susceptibility, influenza virus, immune-related variants, RSV, Medical Microbiology, Virology
Abstract

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.

Published
2021

21. Body size and risk of colorectal cancer molecular defined subtypes and pathways: Mendelian randomization analyses

Author

Papadimitriou, Nikos, Qu, Conghui, Harrison, Tabitha A., Bever, Alaina M., Martin, Richard M., Tsilidis, Konstantinos K., Newcomb, Polly A., Thibodeau, Stephen N., Newton, Christina C., Um, Caroline Y., Obón-Santacana, Mireia, Moreno, Victor, Brenner, Hermann, Mandic, Marko, Chang-Claude, Jenny, Hoffmeister, Michael, Pellatt, Andrew J., Schoen, Robert E., Harlid, Sophia, Ogino, Shuji, Ugai, Tomotaka, Buchanan, Daniel D., Lynch, Brigid M., Gruber, Stephen B., Cao, Yin, Hsu, Li, Huyghe, Jeroen R., Lin, Yi, Steinfelder, Robert S., Sun, Wei, Van Guelpen, Bethany, Zaidi, Syed H., Toland, Amanda E., Berndt, Sonja I., Huang, Wen-Yi, Aglago, Elom K., Drew, David A., French, Amy J., Georgeson, Peter, Giannakis, Marios, Hullar, Meredith, Nowak, Johnathan A., Thomas, Claire E., Le Marchand, Loic, Cheng, Iona, Gallinger, Steven, Jenkins, Mark A., Gunter, Marc J., Campbell, Peter T., Peters, Ulrike, Song, Mingyang, Phipps, Amanda I., and Murphy, Neil

Published
2024
Full Text
View/download PDF

22. Cancer classification using the Immunoscore: a worldwide task force

Author

Galon Jérôme, Pagès Franck, Marincola Francesco M, Angell Helen K, Thurin Magdalena, Lugli Alessandro, Zlobec Inti, Berger Anne, Bifulco Carlo, Botti Gerardo, Tatangelo Fabiana, Britten Cedrik M, Kreiter Sebastian, Chouchane Lotfi, Delrio Paolo, Arndt Hartmann, Asslaber Martin, Maio Michele, Masucci Giuseppe V, Mihm Martin, Vidal-Vanaclocha Fernando, Allison James P, Gnjatic Sacha, Hakansson Leif, Huber Christoph, Singh-Jasuja Harpreet, Ottensmeier Christian, Zwierzina Heinz, Laghi Luigi, Grizzi Fabio, Ohashi Pamela S, Shaw Patricia A, Clarke Blaise A, Wouters Bradly G, Kawakami Yutaka, Hazama Shoichi, Okuno Kiyotaka, Wang Ena, O'Donnell-Tormey Jill, Lagorce Christine, Pawelec Graham, Nishimura Michael I, Hawkins Robert, Lapointe Réjean, Lundqvist Andreas, Khleif Samir N, Ogino Shuji, Gibbs Peter, Waring Paul, Sato Noriyuki, Torigoe Toshihiko, Itoh Kyogo, Patel Prabhu S, Shukla Shilin N, Palmqvist Richard, Nagtegaal Iris D, Wang Yili, D'Arrigo Corrado, Kopetz Scott, Sinicrope Frank A, Trinchieri Giorgio, Gajewski Thomas F, Ascierto Paolo A, and Fox Bernard A

Subjects
Medicine
Abstract

Abstract Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ‘Immunoscore’ into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Published
2012
Full Text
View/download PDF

23. Spatially organized multicellular immune hubs in human colorectal cancer.

Author

Pelka, Karin, Hofree, Matan, Chen, Jonathan, Sarkizova, Siranush, Pirl, Joshua, Jorgji, Vjola, Bejnood, Alborz, Dionne, Danielle, Ge, William, Xu, Katherine, Chao, Sherry, Zollinger, Daniel, Lieb, David, Reeves, Jason, Fuhrman, Christopher, Hoang, Margaret, Delorey, Toni, Nguyen, Lan, Waldman, Julia, Klapholz, Max, Wakiro, Isaac, Cohen, Ofir, Albers, Julian, Smillie, Christopher, Cuoco, Michael, Wu, Jingyi, Su, Mei-Ju, Yeung, Jason, Vijaykumar, Brinda, Magnuson, Angela, Asinovski, Natasha, Moll, Tabea, Goder-Reiser, Max, Applebaum, Anise, Brais, Lauren, DelloStritto, Laura, Denning, Sarah, Phillips, Susannah, Hill, Emma, Meehan, Julia, Frederick, Dennie, Sharova, Tatyana, Kanodia, Abhay, Todres, Ellen, Jané-Valbuena, Judit, Biton, Moshe, Izar, Benjamin, Lambden, Conner, Clancy, Thomas, Bleday, Ronald, Melnitchouk, Nelya, Irani, Jennifer, Kunitake, Hiroko, Berger, David, Srivastava, Amitabh, Hornick, Jason, Ogino, Shuji, Rotem, Asaf, Vigneau, Sébastien, Johnson, Bruce, Corcoran, Ryan, Sharpe, Arlene, Kuchroo, Vijay, Ng, Kimmie, Giannakis, Marios, Nieman, Linda, Boland, Genevieve, Aguirre, Andrew, Anderson, Ana, Rozenblatt-Rosen, Orit, Regev, Aviv, and Hacohen, Nir

Subjects
MSI, MSS, anti-tumor immunity, cell-cell interactions, colorectal cancer, mismatch repair-deficient, mismatch repair-proficient, scRNA-seq, spatial, tumor atlas, Bone Morphogenetic Proteins, Cancer-Associated Fibroblasts, Cell Compartmentation, Cell Line, Tumor, Chemokines, Cohort Studies, Colorectal Neoplasms, DNA Mismatch Repair, Endothelial Cells, Gene Expression Regulation, Neoplastic, Humans, Immunity, Inflammation, Monocytes, Myeloid Cells, Neutrophils, Stromal Cells, T-Lymphocytes, Transcription, Genetic
Abstract

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.

Published
2021

24. Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine.

Author

Dai, Jin, Nishi, Akihiro, Tran, Nathan, Yamamoto, Yasumasa, Dewey, George, Ugai, Tomotaka, and Ogino, Shuji

Subjects
Alzheimer’s disease, breast cancer, health inequality, heterogeneity, laboratory medicine, molecular pathological epidemiology, precision medicine, prevention, social epidemiology, social science, Humans, Molecular Epidemiology, Neoplasms, Pathology, Molecular, Precision Medicine, Social Sciences
Abstract

INTRODUCTION: Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework. AREAS COVERED: Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimers disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimers disease to date. EXPERT OPINION: With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.

Published
2021

25. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

Author

Schernhammer Eva S, Hazra Aditi, Shima Kaori, Tanaka Noriko, Nosho Katsuhiko, Huttenhower Curtis, Baba Yoshifumi, Hunter David J, Giovannucci Edward L, Fuchs Charles S, and Ogino Shuji

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon) constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features. Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing). Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP), microsatellite instability, expression of TP53 (p53), CDKN1A (p21), CTNNB1 (β-catenin), PTGS2 (cyclooxygenase-2), and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6), and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation < 40; N = 22 (2.5%), which were far more than what could be expected by normal distribution]. LINE-1 extreme hypomethylators were significantly associated with younger patients (p = 0.0058). Residual plot by multivariate linear regression showed that LINE-1 extreme hypomethylators clustered as one distinct group, separate from the main tumor group. The multivariate linear regression model could explain 8.4% of the total variability of LINE-1 methylation (R-square = 0.084). Multivariate logistic regression models for binary LINE-1 hypomethylation outcomes (cutoffs of 40, 50 and 60) showed at most fair predictive ability (area under receiver operator characteristics curve < 0.63). Conclusions LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.

Published
2010
Full Text
View/download PDF

26. Postdiagnostic dairy products intake and colorectal cancer survival in US males and females

Author

Liu, Xing, Yang, Wanshui, Wu, Kana, Ogino, Shuji, Wang, Weibing, He, Na, Chan, Andrew T, Zhang, Zuo-Feng, Meyerhardt, Jeffrey A, Giovannucci, Edward, and Zhang, Xuehong

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Prevention, Digestive Diseases, Colo-Rectal Cancer, Clinical Research, Cancer, Good Health and Well Being, Adult, Aged, Colorectal Neoplasms, Dairy Products, Diet, Female, Health Occupations, Humans, Male, United States, dairy, high-fat dairy, low-fat dairy, colorectal cancer, survival, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundTo evaluate the association between postdiagnostic dairy intake and survival among patients with colorectal cancer (CRC).MethodsThis study analyzed data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Postdiagnostic dairy intake and other dietary and lifestyle factors were obtained from validated questionnaires. Individual dairy items including milk, cheese, yogurt, and so on were reported, and total, high-fat, and low-fat dairy intakes were derived.ResultsA total of 1753 eligible CRC cases were identified until 2012, from which 703 deaths were documented after a median follow-up time of 8.2 y, and 242 were due to CRC. Overall, when comparing those who consumed 21+ servings/wk with

Published
2021

27. Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma

Author

Kirkner Gregory J, Chan Andrew T, Glickman Jonathan N, Suemoto Yuko, Ohnishi Mutsuko, Nosho Katsuhiko, Kawasaki Takako, Mino-Kenudson Mari, Fuchs Charles S, and Ogino Shuji

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Cyclooxygenase-2 (COX-2, PTGS2) plays an important role in colorectal carcinogenesis. COX-2 overexpression in colorectal cancer is inversely associated with microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Evidence suggests that MSI/CIMP+ colorectal cancer may arise through the serrated tumorigenic pathway through various forms of serrated neoplasias. Therefore, we hypothesized that COX-2 may play a less important role in the serrated pathway. Methods By immunohistochemistry, we assessed COX-2 expression in 24 hyperplastic polyps, 7 sessile serrated polyp/adenomas (SSA), 5 mixed polyps with SSA and adenoma, 27 traditional serrated adenomas, 515 non-serrated adenomas (tubular adenoma, tubulovillous adenoma and villous adenoma), 33 adenomas with intramucosal carcinomas, 96 adenocarcinomas with serration (corkscrew gland) and 111 adenocarcinomas without serration. Results Strong (2+) COX-2 overexpression was more common in non-serrated adenomas (28% = 143/515) than in hyperplastic polyps (4.2% = 1/24, p = 0.008) and serrated polyps (7 SSAs and 5 mixed polyps) (0% = 0/12, p = 0.04). Furthermore, any (1+/2+) COX-2 overexpression was more frequent in non-serrated adenomas (60% = 307/515) than in hyperplastic polyps (13% = 3/24, p < 0.0001) and serrated polyps (SSAs and mixed polyps) (25% = 3/12, p = 0.03). Traditional serrated adenomas and non-serrated adenomas showed similar frequencies of COX-2 overexpression. Regardless of serration, COX-2 overexpression was frequent (~85%) in colorectal adenocarcinomas. Tumor location was not significantly correlated with COX-2 overexpression, although there was a trend towards higher frequencies of COX-2 overexpression in distal tumors (than proximal tumors) among hyperplastic polyps, SSAs, mixed polyps, traditional serrated adenomas and adenocarcinomas. Conclusion COX-2 overexpression is infrequent in hyperplastic polyp, SSA and mixed polyp with SSA and adenoma, compared to non-serrated and serrated adenoma. COX-2 overexpression becomes more frequent as tumors progress to higher grade neoplasias. Our observations suggest that COX-2 may play a less significant role in the serrated pathway of tumorigenesis; however, COX-2 may still play a role in later stage of the serrated pathway.

Published
2008
Full Text
View/download PDF

29. 18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high

Author

Kirkner Gregory J, Kawasaki Takako, Ogino Shuji, Ohnishi Mutsuko, and Fuchs Charles S

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background: The CpG island methylator phenotype (CIMP) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, associated with microsatellite instability-high (MSI-high) and BRAF mutations. 18q loss of heterozygosity (LOH) commonly present in colorectal cancer with chromosomal instability (CIN) is associated with global hypomethylation in tumor cell. A recent study has shown an inverse correlation between CIN and CIMP (determined by MINTs, p16, p14 and MLH1 methylation) in colorectal cancer. However, no study has examined 18q LOH in relation to CIMP-high, CIMP-low (less extensive promoter methylation) and CIMP-0 (CIMP-negative), determined by quantitative DNA methylation analysis. Methods: Utilizing MethyLight technology (real-time PCR), we quantified DNA methylation in 8 CIMP-specific promoters {CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1} in 758 non-MSI-high colorectal cancers obtained from two large prospective cohorts. Using four 18q microsatellite markers (D18S55, D18S56, D18S67 and D18S487) and stringent criteria for 18q LOH, we selected 374 tumors (236 LOH-positive tumors with ≥ 2 markers showing LOH; and 138 LOH-negative tumors with ≥ 3 informative markers and no LOH). Results: CIMP-0 (0/8 methylated promoters) was significantly more common in 18q LOH-positive tumors (59% = 139/236, p = 0.002) than 18q LOH-negative tumors (44% = 61/138), while CIMP-low/high (1/8–8/8 methylated promoters) was significantly more common (56%) in 18q LOH-negative tumors than 18q LOH-positive tumors (41%). These relations persisted after stratification by sex, location, or the status of MSI, p53 expression (by immunohistochemistry), or KRAS/BRAF mutation. Conclusion: 18q LOH is correlated positively with CIMP-0 and inversely with CIMP-low and CIMP-high. Our findings provide supporting evidence for relationship between CIMP-0 and 18q LOH as well as a molecular difference between CIMP-0 and CIMP-low in colorectal cancer.

Published
2007
Full Text
View/download PDF

30. Elucidating the Risk of Colorectal Cancer for Variants in Hereditary Colorectal Cancer Genes

Author

Wang, Xiaoliang, Huyghe, Jeroen R., Joo, Jihoon E., Georgeson, Peter, Arndt, Volker, Berndt, Sonja I., Bézieau, Stéphane, Bien, Stephanie A., Bishop, D. Timothy, Brenner, Hermann, Brezina, Stefanie, Burnett-Hartman, Andrea, Campbell, Peter T., Casey, Graham, Castellví-Bel, Sergi, Chan, Andrew T., Chang-Claude, Jenny, Chen, Xuechen, Conti, David V., Cremolini, Chiara, Diergaarde, Brenda, Figueiredo, Jane C., FitzGerald, Liesel M., Gago-Dominguez, Manuela, Gallinger, Steven, Giles, Graham G., Gsu, Andrea, Gunter, Marc J., Hampe, Jochen, Hampel, Heather, Harrison, Tabitha A., Hoffmeister, Michael, Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lenz, Heinz-Josef, Li, Christopher I., Li, Li, Lin, Yi, Lindblom, Annika, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Newton, Christina C., Obón-Santacana, Mireia, Ogino, Shuji, Pai, Rish K., Palmer, Julie R., Pearlman, Rachel, Pharoah, Paul D.P., Phipps, Amanda I., Platz, Elizabeth A., Potter, John D., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Stadler, Zsofia K., Steinfelder, Robert S., Thibodeau, Stephen N., Ulrich, Cornelia M., Um, Caroline Y., van Duijnhoven, Franzel J.B., Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Weinstein, Stephanie J., White, Emily, Winship, Ingrid M., Wolk, Alicja, Gruber, Stephen B., Jenkins, Mark A., Mahmood, Khalid, Thomas, Minta, Qu, Conghui, Hsu, Li, Buchanan, Daniel D., and Peters, Ulrike

Published
2023
Full Text
View/download PDF

31. Bayesian risk prediction model for colorectal cancer mortality through integration of clinicopathologic and genomic data

Author

Zhao, Melissa, Lau, Mai Chan, Haruki, Koichiro, Väyrynen, Juha P., Gurjao, Carino, Väyrynen, Sara A., Dias Costa, Andressa, Borowsky, Jennifer, Fujiyoshi, Kenji, Arima, Kota, Hamada, Tsuyoshi, Lennerz, Jochen K., Fuchs, Charles S., Nishihara, Reiko, Chan, Andrew T., Ng, Kimmie, Zhang, Xuehong, Meyerhardt, Jeffrey A., Song, Mingyang, Wang, Molin, Giannakis, Marios, Nowak, Jonathan A., Yu, Kun-Hsing, Ugai, Tomotaka, and Ogino, Shuji

Published
2023
Full Text
View/download PDF

33. Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients

Author

Tsai, Pei-Chen, Lee, Tsung-Hua, Kuo, Kun-Chi, Su, Fang-Yi, Lee, Tsung-Lu Michael, Marostica, Eliana, Ugai, Tomotaka, Zhao, Melissa, Lau, Mai Chan, Väyrynen, Juha P., Giannakis, Marios, Takashima, Yasutoshi, Kahaki, Seyed Mousavi, Wu, Kana, Song, Mingyang, Meyerhardt, Jeffrey A., Chan, Andrew T., Chiang, Jung-Hsien, Nowak, Jonathan, Ogino, Shuji, and Yu, Kun-Hsing

Published
2023
Full Text
View/download PDF

34. The urgent need for integrated science to fight COVID-19 pandemic and beyond

Author

Moradian, Negar, Ochs, Hans D, Sedikies, Constantine, Hamblin, Michael R, Camargo, Carlos A, Martinez, J Alfredo, Biamonte, Jacob D, Abdollahi, Mohammad, Torres, Pedro J, Nieto, Juan J, Ogino, Shuji, Seymour, John F, Abraham, Ajith, Cauda, Valentina, Gupta, Sudhir, Ramakrishna, Seeram, Sellke, Frank W, Sorooshian, Armin, Wallace Hayes, A, Martinez-Urbistondo, Maria, Gupta, Manoj, Azadbakht, Leila, Esmaillzadeh, Ahmad, Kelishadi, Roya, Esteghamati, Alireza, Emam-Djomeh, Zahra, Majdzadeh, Reza, Palit, Partha, Badali, Hamid, Rao, Idupulapati, Saboury, Ali Akbar, Jagan Mohan Rao, L, Ahmadieh, Hamid, Montazeri, Ali, Fadini, Gian Paolo, Pauly, Daniel, Thomas, Sabu, Moosavi-Movahed, Ali A, Aghamohammadi, Asghar, Behmanesh, Mehrdad, Rahimi-Movaghar, Vafa, Ghavami, Saeid, Mehran, Roxana, Uddin, Lucina Q, Von Herrath, Matthias, Mobasher, Bahram, and Rezaei, Nima

Subjects
Biomedical and Clinical Sciences, Health Sciences, Infection, Good Health and Well Being, Betacoronavirus, Biomedical Research, COVID-19, Coronavirus Infections, Delivery of Health Care, Integrated, Emergencies, Health Services Needs and Demand, History, 21st Century, Humans, Interdisciplinary Communication, Interdisciplinary Studies, Pandemics, Pneumonia, Viral, Public Health, SARS-CoV-2, Coronavirus, Complex problems, Collaboration, Interdisciplinarity, Public health, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

Published
2020

35. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.

Author

Zaidi, Syed H, Harrison, Tabitha A, Phipps, Amanda I, Steinfelder, Robert, Trinh, Quang M, Qu, Conghui, Banbury, Barbara L, Georgeson, Peter, Grasso, Catherine S, Giannakis, Marios, Adams, Jeremy B, Alwers, Elizabeth, Amitay, Efrat L, Barfield, Richard T, Berndt, Sonja I, Borozan, Ivan, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Cao, Yin, Chan, Andrew T, Chang-Claude, Jenny, Connolly, Charles M, Drew, David A, Farris, Alton Brad, Figueiredo, Jane C, French, Amy J, Fuchs, Charles S, Garraway, Levi A, Gruber, Steve, Guinter, Mark A, Hamilton, Stanley R, Harlid, Sophia, Heisler, Lawrence E, Hidaka, Akihisa, Hopper, John L, Huang, Wen-Yi, Huyghe, Jeroen R, Jenkins, Mark A, Krzyzanowski, Paul M, Lemire, Mathieu, Lin, Yi, Luo, Xuemei, Mardis, Elaine R, McPherson, John D, Miller, Jessica K, Moreno, Victor, Mu, Xinmeng Jasmine, Nishihara, Reiko, Papadopoulos, Nickolas, Pasternack, Danielle, Quist, Michael J, Rafikova, Adilya, Reid, Emma EG, Shinbrot, Eve, Shirts, Brian H, Stein, Lincoln D, Teney, Cherie D, Timms, Lee, Um, Caroline Y, Van Guelpen, Bethany, Van Tassel, Megan, Wang, Xiaolong, Wheeler, David A, Yung, Christina K, Hsu, Li, Ogino, Shuji, Gsur, Andrea, Newcomb, Polly A, Gallinger, Steven, Hoffmeister, Michael, Campbell, Peter T, Thibodeau, Stephen N, Sun, Wei, Hudson, Thomas J, and Peters, Ulrike

Abstract

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Published
2020

36. The urgent need for integrated science to fight COVID-19 pandemic and beyond.

Author

Ramakrishna, Seeram, Sellke, Frank, Sorooshian, Armin, Wallace Hayes, A, Martinez-Urbistondo, Maria, Gupta, Manoj, Azadbakht, Leila, Esmaillzadeh, Ahmad, Kelishadi, Roya, Esteghamati, Alireza, Emam-Djomeh, Zahra, Majdzadeh, Reza, Palit, Partha, Badali, Hamid, Rao, Idupulapati, Saboury, Ali, Jagan Mohan Rao, L, Ahmadieh, Hamid, Montazeri, Ali, Fadini, Gian, Pauly, Daniel, Thomas, Sabu, Moosavi-Movahed, Ali, Aghamohammadi, Asghar, Behmanesh, Mehrdad, Rahimi-Movaghar, Vafa, Ghavami, Saeid, Mehran, Roxana, Uddin, Lucina, Von Herrath, Matthias, Mobasher, Bahram, Rezaei, Nima, Moradian, Negar, Ochs, Hans, Sedikies, Constantine, Hamblin, Michael, Camargo, Carlos, Martinez, J, Biamonte, Jacob, Abdollahi, Mohammad, Torres, Pedro, Nieto, Juan, Ogino, Shuji, Seymour, John, Abraham, Ajith, Cauda, Valentina, and Gupta, Sudhir

Subjects
COVID-19, Collaboration, Complex problems, Coronavirus, Interdisciplinarity, Public health, Betacoronavirus, Biomedical Research, COVID-19, Coronavirus Infections, Delivery of Health Care, Integrated, Emergencies, Health Services Needs and Demand, History, 21st Century, Humans, Interdisciplinary Communication, Interdisciplinary Studies, Pandemics, Pneumonia, Viral, Public Health, SARS-CoV-2
Abstract

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the worlds scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemics consequences and prevent recurrences of similar pandemics.

Published
2020

37. Functional informed genome‐wide interaction analysis of body mass index, diabetes and colorectal cancer risk

Author

Xia, Zhiyu, Su, Yu‐Ru, Petersen, Paneen, Qi, Lihong, Kim, Andre E, Figueiredo, Jane C, Lin, Yi, Nan, Hongmei, Sakoda, Lori C, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bien, Stephanie, Buchanan, Daniel D, Casey, Graham, Chan, Andrew T, Conti, David V, Drew, David A, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Gruber, Stephen B, Gunter, Marc J, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Le Marchand, Loic, Lewinger, Juan P, Li, Li, Lindor, Noralane M, Moreno, Victor, Murphy, Neil, Nassir, Rami, Newcomb, Polly A, Ogino, Shuji, Rennert, Gad, Song, Mingyang, Wang, Xiaoliang, Wolk, Alicja, Woods, Michael O, Brenner, Hermann, White, Emily, Slattery, Martha L, Giovannucci, Edward L, Chang‐Claude, Jenny, Pharoah, Paul DP, Hsu, Li, Campbell, Peter T, and Peters, Ulrike

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Digestive Diseases, Colo-Rectal Cancer, Women's Health, Nutrition, Genetics, Cancer, Human Genome, Obesity, Diabetes, 2.1 Biological and endogenous factors, Metabolic and endocrine, ATPases Associated with Diverse Cellular Activities, Aged, Body Mass Index, Colorectal Neoplasms, Databases, Genetic, Diabetes Mellitus, Type 2, Female, Gene Expression, Genotype, Hepatocyte Nuclear Factor 3-alpha, Humans, Male, Microtubule-Associated Proteins, Middle Aged, Phenotype, Proteasome Endopeptidase Complex, Protein Tyrosine Phosphatase, Non-Receptor Type 2, Sex Factors, Sialic Acid Binding Ig-like Lectin 3, Voltage-Gated Sodium Channel beta-1 Subunit, BMI, colorectal cancer, diabetes, gene expression, gene-environmental interaction, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

BackgroundBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.MethodsTo improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR

Published
2020

38. Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases

Author

Ugai, Tomotaka, Akimoto, Naohiko, Haruki, Koichiro, Harrison, Tabitha A., Cao, Yin, Qu, Conghui, Chan, Andrew T., Campbell, Peter T., Berndt, Sonja I., Buchanan, Daniel D., Cross, Amanda J., Diergaarde, Brenda, Gallinger, Steven J., Gunter, Marc J., Harlid, Sophia, Hidaka, Akihisa, Hoffmeister, Michael, Brenner, Hermann, Chang-Claude, Jenny, Hsu, Li, Jenkins, Mark A., Lin, Yi, Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Nishihara, Reiko, Obon-Santacana, Mireia, Pai, Rish K., Sakoda, Lori C., Schoen, Robert E., Slattery, Martha L., Sun, Wei, Amitay, Efrat L., Alwers, Elizabeth, Thibodeau, Stephen N., Toland, Amanda E., Van Guelpen, Bethany, Zaidi, Syed H., Potter, John D., Meyerhardt, Jeffrey A., Giannakis, Marios, Song, Mingyang, Nowak, Jonathan A., Peters, Ulrike, Phipps, Amanda I., and Ogino, Shuji

Published
2023
Full Text
View/download PDF

39. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author

Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike

Published
2023
Full Text
View/download PDF

42. Universal research index: An inclusive metric to quantify scientific research output

Author

Keshavarz-Fathi, Mahsa, Yazdanpanah, Niloufar, Kolahchi, Sajad, Ziaei, Heliya, Darmstadt, Gary L., Dorigo, Tommaso, Dochy, Filip, Levin, Lisa, Thongboonkerd, Visith, Ogino, Shuji, Chen, Wei-Hsin, Perc, Matjaz, Tremblay, Mark S., Olusanya, Bolajoko O., Rao, Idupulapati M., Hatziargyriou, Nikos, Moradi-Lakeh, Maziar, Bella, Federico, Rosivall, Laszlo, Gandomi, Amir H., Sorooshian, Armin, Gupta, Manoj, Gal, Ciprian, Lozano, Andres M., Weaver, Connie, Tanzer, Michael, Poggi, Alessandro, Sepanlou, Sadaf G., Weiskirchen, Ralf, Jambrak, Anet Režek, Torres, Pedro J., Capanoglu, Esra, Barba, Francisco J., Ernest, Chua Kian Jon, Sigman, Mariano, Pluchino, Stefano, Gharehpetian, Gevork B., Fereshtehnejad, Seyed-Mohammad, Yang, Muh-Hwa, Thomas, Sabu, Cai, Wenju, Comini, Elisabetta, Scolding, Neil J., Myles, Paul S., Nieto, Juan J., Perry, George, Sedikides, Constantine, and Rezaei, Nima

Published
2023
Full Text
View/download PDF

45. Western-Style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses From Two Large Prospective Cohort Studies

Author

Arima, Kota, Zhong, Rong, Ugai, Tomotaka, Zhao, Melissa, Haruki, Koichiro, Akimoto, Naohiko, Lau, Mai Chan, Okadome, Kazuo, Mehta, Raaj S., Väyrynen, Juha P., Kishikawa, Junko, Twombly, Tyler S., Shi, Shanshan, Fujiyoshi, Kenji, Kosumi, Keisuke, Ogata, Yoko, Baba, Hideo, Wang, Fenglei, Wu, Kana, Song, Mingyang, Zhang, Xuehong, Fuchs, Charles S., Sears, Cynthia L., Willett, Walter C., Giovannucci, Edward L., Meyerhardt, Jeffrey A., Garrett, Wendy S., Huttenhower, Curtis, Chan, Andrew T., Nowak, Jonathan A., Giannakis, Marios, and Ogino, Shuji

Published
2022
Full Text
View/download PDF

47. Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting

Author

Yao, Song, Campbell, Peter T., Ugai, Tomotaka, Gierach, Gretchen, Abubakar, Mustapha, Adalsteinsson, Viktor, Almeida, Jonas, Brennan, Paul, Chanock, Stephen, Golub, Todd, Hanash, Samir, Harris, Curtis, Hathaway, Cassandra A., Kelsey, Karl, Landi, Maria Teresa, Mahmood, Faisal, Newton, Christina, Quackenbush, John, Rodig, Scott, Schultz, Nikolaus, Tearney, Guillermo, Tworoger, Shelley S., Wang, Molin, Zhang, Xuehong, Garcia-Closas, Montserrat, Rebbeck, Timothy R., Ambrosone, Christine B., and Ogino, Shuji

Published
2022
Full Text
View/download PDF

48. A novel calibration framework for survival analysis when a binary covariate is measured at sparse time points

Author

Nevo, Daniel, Hamada, Tsuyoshi, Ogino, Shuji, and Wang, Molin

Subjects
Statistics - Applications, Statistics - Methodology, Statistics - Other Statistics
Abstract

The goals in clinical and cohort studies often include evaluation of the association of a time-dependent binary treatment or exposure with a survival outcome. Recently, several impactful studies targeted the association between aspirin-taking and survival following colorectal cancer diagnosis. Due to surgery, aspirin-taking value is zero at baseline and may change its value to one at some time point. Estimating this association is complicated by having only intermittent measurements on aspirin-taking. Naive, commonly-used, methods can lead to substantial bias. We present a class of calibration models for the distribution of the time of status change of the binary covariate. Estimates obtained from these models are then incorporated into the proportional hazard partial likelihood in a natural way. We develop nonparametric, semiparametric and parametric calibration models, and derive asymptotic theory for the methods that we implement in the aspirin and colorectal cancer study. Our methodology allows to include additional baseline variables in the calibration models for the status change time of the binary covariate. We further develop a risk-set calibration approach that is more useful in settings in which the association between the binary covariate and survival is strong.

Published
2018
Full Text
View/download PDF

49. Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment.

Author

Lau, Mai Chan, Borowsky, Jennifer, Väyrynen, Juha P., Haruki, Koichiro, Zhao, Melissa, Dias Costa, Andressa, Gu, Simeng, da Silva, Annacarolina, Ugai, Tomotaka, Arima, Kota, Nguyen, Minh N., Takashima, Yasutoshi, Yeong, Joe, Tai, David, Hamada, Tsuyoshi, Lennerz, Jochen K., Fuchs, Charles S., Wu, Catherine J., Meyerhardt, Jeffrey A., and Ogino, Shuji

Subjects
CLUSTERING algorithms, SUPERVISED learning, TUMOR-infiltrating immune cells, PARALLEL algorithms, EPITHELIAL tumors
Abstract

Background: Growing evidence supports the importance of characterizing the organizational patterns of various cellular constituents in the tumor microenvironment in precision oncology. Most existing data on immune cell infiltrates in tumors, which are based on immune cell counts or nearest neighbor-type analyses, have failed to fully capture the cellular organization and heterogeneity. Methods: We introduce a computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), that jointly measures immune cell partitioning between tumor epithelial and stromal areas and immune cell clustering versus dispersion. As proof-of-principle, we applied TIPC to a prospective cohort incident tumor biobank containing 931 colorectal carcinoma cases. TIPC identified tumor subtypes with unique spatial patterns between tumor cells and T lymphocytes linked to certain molecular pathologic and prognostic features. T lymphocyte identification and phenotyping were achieved using multiplexed (multispectral) immunofluorescence. In a separate hepatocellular carcinoma cohort, we replaced the stromal component with specific immune cell types—CXCR3+CD68+ or CD8+—to profile their spatial relationships with CXCL9+CD68+ cells. Results: Six unsupervised TIPC subtypes based on T lymphocyte distribution patterns were identified, comprising two cold and four hot subtypes. Three of the four hot subtypes were associated with significantly longer colorectal cancer (CRC)-specific survival compared to a reference cold subtype. Our analysis showed that variations in T-cell densities among the TIPC subtypes did not strictly correlate with prognostic benefits, underscoring the prognostic significance of immune cell spatial patterns. Additionally, TIPC revealed two spatially distinct and cell density-specific subtypes among microsatellite instability-high colorectal cancers, indicating its potential to upgrade tumor subtyping. TIPC was also applied to additional immune cell types, eosinophils and neutrophils, identified using morphology and supervised machine learning; here two tumor subtypes with similarly low densities, namely 'cold, tumor-rich' and 'cold, stroma-rich', exhibited differential prognostic associations. Lastly, we validated our methods and results using The Cancer Genome Atlas colon and rectal adenocarcinoma data (n = 570). Moreover, applying TIPC to hepatocellular carcinoma cases (n = 27) highlighted critical cell interactions like CXCL9-CXCR3 and CXCL9-CD8. Conclusions: Unsupervised discoveries of microgeometric tissue organizational patterns and novel tumor subtypes using the TIPC algorithm can deepen our understanding of the tumor immune microenvironment and likely inform precision cancer immunotherapy. Author summary: We have developed a computational tool called the Tumor-Immune Partitioning and Clustering (TIPC) algorithm, designed to reveal the intricate organization of immune cells within the tumor microenvironment. Traditionally, studies have mainly focused on counting these cells or examining their proximity to one another. Those approaches often underestimate the complex roles of immune cells in tumors. With TIPC, we have uncovered distinct patterns in the arrangement of immune cells across different tumor regions. This advancement has enabled us to identify tumor subtypes that were previously undetectable with existing methods. Our new method can determine which tumors are likely to have longer survival rates or respond better to immunotherapy, based on the layout of immune cells rather than merely their numbers. This breakthrough has significant implications for cancer research, highlighting the importance of understanding the spatial patterns of immune cells. Such knowledge is crucial for selecting appropriate patients for specific treatments and for assessing the potential effectiveness of immunotherapy. By tailoring treatment plans to the unique cellular landscapes of each tumor, we can potentially improve outcomes and provide more personalized and effective cancer care. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

50. Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702.

Author

Nowak, Jonathan Andrew, Shi, Qian, Twombly, Tyler, Pederson, Levi D., Ma, Chao, Väyrynen, Juha P., Zhao, Melissa M., Takashima, Yasutoshi, Shergill, Ardaman, Kumar, Pankaj, Couture, Felix, Kuebler, J. Phillip, Krishnamurthi, Smitha S., Tan, Benjamin R., O'Reilly, Eileen M., Shields, Anthony F., Ogino, Shuji, Aleshin, Alexey, and Meyerhardt, Jeffrey A.

Published
2025
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results