Common markers of proliferation

Whitfield, Michael L.; George, Lacy K.; Grant, Gavin D.; Perou, Charles M.

doi:10.1038/nrc1802

Cited by 653Gene expression and cancer classificationBreast Cancer Treatment StudiesCancer-related Molecular Pathways

Common markers of proliferation

Whitfield, Michael L., George, Lacy K., Grant, Gavin D., Perou, Charles M.·2006·Nature Reviews Cancer

DOI 10.1038/nrc1802

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Abstract

When normal tissue and tumour samples are compared by microarray analysis, the biggest differences most often occur in the expression levels of genes that control cell proliferation. However, this difference is detected whenever mRNA samples that are taken from two cell populations with different proliferation rates are compared. Although the exact genes that comprise this 'proliferation signature' often differ, they are almost always genes that are involved in the fundamental process of cell proliferation. Can the proliferation signature be used to improve our understanding of the cell cycle and cancer pathogenesis, as well as being used as a biomarker for cancer diagnosis and prognosis?

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“It is one of the dominant gene signatures for highly proliferative cells observed across multiple tumor types and is highly overexpressed in several cancers [81,82,83].”
Background
Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK–ERK linkage
Provenzano, P. P., Inman, D. R., Eliceiri, K. W., & Keely, P. J. (2009) · Oncogene · doi:10.1038/onc.2009.299 · Cited by 679 · see citing works
“Consistent with these findings, immunofluorescent microscopy of 3D cultures confirmed that increased matrix stiffness induced vinculin and paxillin-positive 3D-matrix adhesions (Fig 2B).”
Influential
Focal Gains of <i>VEGFA</i> and Molecular Classification of Hepatocellular Carcinoma
Chiang, D. Y., Villanueva, A., Hoshida, Y., Peix, J., Newell, P., Minguez, B., LeBlanc, A. C., Donovan, D. J., Thung, S. N., Solé, M., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0742 · Cited by 719 · see citing works
Decoding global gene expression programs in liver cancer by noninvasive imaging
Segal, E., Sirlin, C. B., Ooi, C., Adler, A. S., Gollub, J., Chen, X., Chan, B. K., Matcuk, G. R., Barry, C. T., Chang, H. Y., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1306 · Cited by 629 · see citing works
“The 'venous invasion signature' comprises genes involved in cell proliferation ( CDK4 , CDC20 , MCM5 ) and matrix invasion ( ADAMTS1 , MMP14, SPARCL1 )—genes known to be induced in other HCC data sets and indeed in many types of cancer”
Background
Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors
Kosinski, C., Li, V. S. W., Chan, A. S. Y., Zhang, J., Ho, C., Tsui, W. Y., Chan, T. L., Mifflin, R. C., Powell, D. W., Yuen, S. T., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707210104 · Cited by 596 · see citing works
Most Random Gene Expression Signatures Are Significantly Associated with Breast Cancer Outcome
Venet, D., Dumont, J. E., & Detours, V. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002240 · Cited by 594 · see citing works
“A proliferation cluster was noticed in early breast cancer microarray studies [50–52], and proliferation is the major variable behind gene expression-based breast cancer prognosis [7–9].”
Background
Ki-67 acts as a biological surfactant to disperse mitotic chromosomes
Cuylen‐Haering, S., Blaukopf, C., Politi, A. Z., Müller‐Reichert, T., Neumann, B., Poser, I., Ellenberg, J., Hyman, A. A., & Gerlich, D. W. (2016) · Nature · doi:10.1038/nature18610 · Cited by 550 · see citing works
The DREAM complex: master coordinator of cell cycle-dependent gene expression
Sadasivam, S., & DeCaprio, J. A. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3556 · Cited by 524 · see citing works
Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling
Provenzano, P. P., & Keely, P. J. (2011) · Journal of Cell Science · doi:10.1242/jcs.067009 · Cited by 494 · see citing works
“Indeed, culturing mammary epithelial cells in matrices with high stiffness increases the expression of genes that have been identified as the breast carcinoma ‘proliferation signature’ (Whitfield et al., 2006), which negatively correlates with patient survival as shown by us and others (Provenzano et al.”
BackgroundInfluential
Ki-67 protein as a tumour proliferation marker
Menon, S. S., Guruvayoorappan, C., Sakthivel, K. M., & Rasmi, R. R. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.01.011 · Cited by 485 · see citing works
Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas
Piunti, A., Hashizume, R., Morgan, M. A., Bartom, E. T., Horbinski, C. M., Marshall, S. A., Rendleman, E. J., Ma, Q., Takahashi, Y.-H., Woodfin, A. R., et al. (2017) · Nature Medicine · doi:10.1038/nm.4296 · Cited by 445 · see citing works
Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes
Garcia‐Manero, G., Yang, H., Bueso-Ramos, C., Ferrajoli, A., Cortes, J. E., Wierda, W. G., Faderl, S. H., Koller, C. A., Morris, G., Rosner, G. L., et al. (2007) · Blood · doi:10.1182/blood-2007-06-098061 · Cited by 460 · see citing works
“Median platelet count, 109/L (range) 36 (5-232)”
Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment
Zheng, Y., Chen, Z., Han, Y., Li, H., Zou, X., Zhou, B., Hu, R., Hao, J., Bai, S., Xiao, H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20019-0 · Cited by 460 · see citing works
Progenitor identification and SARS-CoV-2 infection in human distal lung organoids
Salahudeen, A. A., Choi, S. S., Rustagi, A., Zhu, J., van Unen, V., de la O, S. M., Flynn, R. A., Margalef-Català, M., Santos, A. J. M., Ju, J., et al. (2020) · Nature · doi:10.1038/s41586-020-3014-1 · Cited by 416 · see citing works
T cell fate and clonality inference from single-cell transcriptomes
(2016) · doi:10.1038/nmeth.3800 · Cited by 434 · see citing works
“For plotting gene expression for each cell within ICA space, 259 genes indicating a Th1-like fate and seven indicators of proliferation (Mki67, Mybl2, Bub1, Plk1, Ccne1, Ccnd1, Ccnb1) were taken from previous work 32,35 and their expression levels (in TPM) were summed for each cell.”
Method
Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin
Milano, A., Pendergrass, S. A., Sargent, J. L., George, L. K., McCalmont, T. H., Connolly, M. K., & Whitfield, M. L. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002696 · Cited by 384 · see citing works
“The proliferation signature is defined as genes that are expressed only when cells are dividing [46].”
BackgroundSelf-citation
Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade
Ouzounova, M., Lee, E., Piranlioglu, R., Andaloussi, A. E., Kolhe, R. B., Demirci, M. F., Marasco, D., Asm, I., Chadli, A., Hassan, K. A., et al. (2017) · Nature Communications · doi:10.1038/ncomms14979 · Cited by 371 · see citing works
Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer
Li, J., Wu, C., Hu, H., Qin, G., Wu, X., Bai, F., Zhang, J., Cai, Y., Huang, Y. J., Wang, C., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.04.011 · Cited by 372 · see citing works
Integrative Analysis of Head and Neck Cancer Identifies Two Biologically Distinct HPV and Three Non-HPV Subtypes
Keck, M. K., Zuo, Z., Khattri, A., Stricker, T. P., Brown, C. D., Imanguli, M. M., Rieke, D. T., Endhardt, K., Fang, P., Brägelmann, J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2481 · Cited by 369 · see citing works
“Consistently, a published proliferation signature also indicates that the CL super-group has a higher proliferation rate compared to the other groups (Supplementary Figure S4) (23).”
Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myélome
Decaux, O., Lodé, L., Magrangeas, F., Guérin‐Charbonnel, C., Gouraud, W., Jézéquel, P., Attal, M., Harousseau, J., Moreau, P., Bataille, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.8545 · Cited by 372 · see citing works
Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks
Fischer, M., Grossmann, P., Padi, M., & DeCaprio, J. A. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw523 · Cited by 330 · see citing works
“CC gene expression signatures help to stratify cancer patients into risk groups (76).”
Background
Targeting Cyclin-Dependent Kinases in Human Cancers: From Small Molecules to Peptide Inhibitors
Peyressatre, M., Prével, C., Pellerano, M., & Morris, M. C. (2015) · Cancers · doi:10.3390/cancers7010179 · Cited by 345 · see citing works
A clinically relevant gene signature in triple negative and basal-like breast cancer
Rody, A., Karn, T., Liedtke, C., Pusztai, L., Ruckhaeberle, E., Hanker, L., Gaetje, R., Solbach, C., Ahr, A., Metzler, D., et al. (2011) · Breast Cancer Research · doi:10.1186/bcr3035 · Cited by 332 · see citing works
“74 47 BUB1, CDC2, STK6, BIRC5, TOP2A, [35]”
Background
Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases
Ota, M., Nagafuchi, Y., Hatano, H., Ishigaki, K., Terao, C. C., Takeshima, Y., Yanaoka, H., Kobayashi, S., Okubo, M., Shirai, H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.056 · Cited by 322 · see citing works
Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review
Luporsi, É., André, F., Spyratos, F., Martin, P., Jacquemier, J. D., Penault-Llorca, F. M., Tubiana-Mathieu, N., Sigal‐Zafrani, B., Arnould, L., Gompel, A., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1837-z · Cited by 320 · see citing works
“Several genes coding for proliferation factors, a key biological driver, are targeted in these genomic profiling tests [12, 26, 58, 112, 113].”
Background
FOXM1, a typical proliferation-associated transcription factor
Wierstra, I., & Alves, J. (2007) · Biological Chemistry · doi:10.1515/bc.2007.159 · Cited by 313 · see citing works
“Like many other members of this proliferation signature, FOXM1 is a cell-cycle-regulated gene (Whitfield et al., 2006), i.e., it is periodically expressed during the cell cycle in synchronized HeLa cells with peak expression of FOXM1 in G2/M phase (Whitfield et al., 2002).”
Background
Integrated Genome-Wide DNA Copy Number and Expression Analysis Identifies Distinct Mechanisms of Primary Chemoresistance in Ovarian Carcinomas
Etemadmoghadam, D., DeFazio, A., Beroukhim, R., Mermel, C. H., George, J., Getz, G. A., Tothill, R. W., Okamoto, A., Raeder, M. B., Chenevix‐Trench, G., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1564 · Cited by 302 · see citing works
Microvesicles from human adipose stem cells promote wound healing by optimizing cellular functions via AKT and ERK signaling pathways
Ren, S., Chen, J., Duscher, D., Liu, Y., Guo, G., Kang, Y., Xiong, H., Zhan, P., Wang, Y., Wang, C., et al. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1152-x · Cited by 292 · see citing works
Lung Squamous Cell Carcinoma mRNA Expression Subtypes Are Reproducible, Clinically Important, and Correspond to Normal Cell Types
Wilkerson, M. D., Yin, X., Hoadley, K. A., Liu, Y., Hayward, M. C., Cabanski, C. R., Muldrew, K. L., Miller, C. R., Randell, S. H., Socinski, M. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0199 · Cited by 279 · see citing works
Self-citation
Global DNA Hypomethylation in Epithelial Ovarian Cancer: Passive Demethylation and Association with Genomic Instability
Zhang, W., Klinkebiel, D. L., Barger, C. J., Pandey, S., Guda, C., Miller, A., Akers, S. N., Odunsi, K. O., & Karpf, A. R. (2020) · Cancers · doi:10.3390/cancers12030764 · Cited by 277 · see citing works
“Normalization Cancers 2020, 12, 764 12 of 25 of DNMTs and UHRF1 to other markers of cancer cell proliferation, including PLK1 and BUB1 [44], provided similar results as seen with MKI67 normalization (Figure S11 and Figure S12).”
ResultInfluential
Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria
Mehta, S., Cronkite, D., Basavappa, M., Saunders, T. L., Adiliaghdam, F., Amatullah, H., Morrison, S. A., Pagan, J., Anthony, R., Tonnerre, P., et al. (2017) · Science immunology · doi:10.1126/sciimmunol.aal2192 · Cited by 368 · see citing works
The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas
Herschkowitz, J. I., He, X., Fan, C., & Perou, C. M. (2008) · Breast Cancer Research · doi:10.1186/bcr2142 · Cited by 255 · see citing works
“It should be noted, however, that several groups have independently identified different gene lists that contain a large number of so-called proliferation/RB-pathway genes [13,32-35] and it was expected that the RB-LOH signature would be a strong prognostic profile.”
BackgroundSelf-citation
Biophysics of tumor microenvironment and cancer metastasis – a mini review
Emon, B., Bauer, J., Jain, Y., Jung, B., & Saif, T. (2018) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2018.07.003 · Cited by 245 · see citing works
“[85] suggested that high-stiffness matrix is necessary for maintaining invasive phenotype and culpable for upregulation of a set of cancer-associated genes dubbed as ‘proliferation signatures’ [52, 86].”
Background
Cancer biomarkers - current perspectives.
Bhatt, A. N., Mathur, R., Farooque, A., Verma, A., & Dwarakanath, B. S. R. (2010) · PubMed · Cited by 238 · see citing works
Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study
Alba, E., Calvo, L., Albanell, J., de la Haba-Rodríguez, J., Lanza, A. A., Chacón, J. I., Sánchez‐Rovira, P., Plazaola, A., García‐Asenjo, J. A. L., Bermejo, B., et al. (2012) · Annals of Oncology · doi:10.1093/annonc/mds132 · Cited by 229 · see citing works
“The main difference between them is the expression of genes related to cell proliferation, such as the E2F regulatory gene [8, 9].”
Background
Coordinating gene expression during the cell cycle
Fischer, M., Schade, A. E., Branigan, T. B., Müller, G. A., & DeCaprio, J. A. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.06.007 · Cited by 218 · see citing works
Simultaneous Multiplexed Measurement of RNA and Proteins in Single Cells
Darmanis, S., Gallant, C. J., Marinescu, V. D., Niklasson, M., Segerman, A., Flamourakis, G., Fredriksson, S., Assarsson, E., Lundberg, M., Nelander, S., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.021 · Cited by 219 · see citing works
“, 2013), and AURKBPROTEIN (Whitfield et al., 2006) (Figure 3C).”
Background
Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis
Nagalla, S., Chou, J. W., Willingham, M. C., Ruiz, J., Vaughn, J. P., Dubey, P., Lash, T. L., Hamilton-Dutoit, S. J., Bergh, J. C. S., Sotiriou, C. P., et al. (2013) · Genome biology · doi:10.1186/gb-2013-14-4-r34 · Cited by 195 · see citing works
“With the aim of discovering genes with statistical associations with breast cancer recurrence, we and others have identified a number of genes with roles in cellular proliferation [1-6], including multi-gene proliferation signatures that directly reflect tumor proliferative capacity [1,4-7].”
Background
Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis
Wang, W., Xu, Y., Wang, L., Zhu, Z., Aodeng, S., Chen, H., Cai, M., Huang, Z., Han, J., Wang, L., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01312-0 · Cited by 195 · see citing works
Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures
Fan, C., Prat, A., Parker, J. S., Liu, Y., Carey, L., Troester, M. A., & Perou, C. M. (2011) · BMC Medical Genomics · doi:10.1186/1755-8794-4-3 · Cited by 192 · see citing works
“Three of these poor prognostic modules were highly enriched with genes involved in cell cycle/ proliferation (MM_Red10), vascular smooth muscle contraction (MUnknown_34), and mRNA processing/splicing (Unknown_9 and MUnknown_1); it is likely that our “undescribed” cell cycle/proliferation module is merely reflecting ma…”
BackgroundSelf-citation
A Cell Proliferation and Chromosomal Instability Signature in Anaplastic Thyroid Carcinoma
Salvatore, G., Nappi, T. C., Salerno, P., Jiang, Y., Garbi, C., Ugolini, C., Miccoli, P., Basolo, F., Castellone, M. D., Cirafici, A. M., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1887 · Cited by 186 · see citing works
“Increased expression of many of these genes, in particular of a core set of 44 of them (‘‘44-gene proliferation cluster’’), is a surrogate measure of tumor cell proliferation and is often associated with poor outcome (11).”
Background
A compact VEGF signature associated with distant metastases and poor outcomes
Hu, Z., Fan, C., Livasy, C., He, X., Oh, D. S., Ewend, M. G., Carey, L., Subramanian, S., West, R. B., Ikpatt, F., et al. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-9 · Cited by 185 · see citing works
“gene sets were identified including proliferation [58], ER status [11,39,40], and fibroblast and/or mesenchymal genes [55,59].”
Self-citation
FOXM1 (Forkhead box M1) in Tumorigenesis
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407190-2.00016-2 · Cited by 183 · see citing works
“Like many other members of this proliferation signature (Whitfield et al., 2006), FOXM1 is a cell cycle-regulated gene (Bar-Joseph et al., 2008; Whitfield et al., 2002, 2006).”
Background
The Transcription Factor FOXM1 (Forkhead box M1)
Wierstra, I. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-407173-5.00004-2 · Cited by 174 · see citing works
RB-pathway disruption in breast cancer
Ertel, A., Dean, J. L., Rui, H., Liu, C., Witkiewicz, A., Knudsen, K. E., & Knudsen, E. S. (2010) · Cell Cycle · doi:10.4161/cc.9.20.13454 · Cited by 173 · see citing works
Prognostic Factors in Prolactin Pituitary Tumors: Clinical, Histological, and Molecular Data from a Series of 94 Patients with a Long Postoperative Follow-Up
Raverot, G., Wierinckx, A., Dantony, E., Auger, C., Chapas, G., Villeneuve, L., Brue, T. C., Figarella-Branger, D. F., Roy, P., Jouanneau, E., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1191 · Cited by 173 · see citing works
Genome-wide transcriptional analysis of the human cell cycle identifies genes differentially regulated in normal and cancer cells
Bar‐Joseph, Z., Siegfried, Z., Brandeis, M., Brors, B., Lu, Y. C., Eils, R., Dynlacht, B. D., & Simon, I. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704723105 · Cited by 169 · see citing works
A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors
Wierinckx, A., Auger, C., Devauchelle, P., Reynaud, A., Chevallier, P., Jan, M., Perrin, G., Fèvre‐Montange, M., Rey, C., Figarella-Branger, D. F., et al. (2007) · Endocrine Related Cancer · doi:10.1677/erc-07-0062 · Cited by 169 · see citing works
“Finally, as recently suggested (Whitfield et al. 2006), the proliferation genes can be used as biomarkers for cancer diagnosis and prognosis.”
Background
How to do quantile normalization correctly for gene expression data analyses
Zhao, Y., Wong, L., & Goh, W. W. B. (2020) · Scientific Reports · doi:10.1038/s41598-020-72664-6 · Cited by 168 · see citing works
Profiling proliferative cells and their progeny in damaged murine hearts
Kretzschmar, K., Post, Y., Bannier-Hélaouët, M., Mattiotti, A., Drost, J., Başak, O., Li, V. S. W., van den Born, M., Gunst, Q. D., Versteeg, D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1805829115 · Cited by 166 · see citing works
“It is therefore widely used in basic cell and developmental biology, in clinical oncology, and in pathology as a general proliferation marker (22).”
Background
Head and neck cancer: from anatomy to biology
Bose, P., Brockton, N. T., & Dort, J. C. (2013) · International Journal of Cancer · doi:10.1002/ijc.28112 · Cited by 161 · see citing works
“and Progression Aberrant cellular proliferation is a hallmark in cancer(16) and proliferation signatures are present in almost all tumors including HNSCC.(17) Most proliferation-associated genes in cancer are oncogenes and increased expression of these genes provides the rationale for their targeted inhibition.”
Background
Single-cell transcriptomics reveals gene expression dynamics of human fetal kidney development
Hochane, M., van den Berg, P. R., Fan, X., Bérenger-Currias, N. M. L. P., Adegeest, E., Bialecka, M., Nieveen, M. C., Menschaart, M., Lopes, S. M. C. D. S., & Semrau, S. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000152 · Cited by 160 · see citing works
“Cluster average cell cycle scores, calculated by Cyclone [15] as well as average expression of proliferation markers [16], are indicated by colored circles below each cluster (Z-score of the mean score or mean expression).”
BackgroundMethodInfluential
Synthetic lethality-mediated precision oncology via the tumor transcriptome
Lee, J. S., Nair, N. U., Dinstag, G., Chapman, L. M., Chung, Y., Wang, K., Sinha, S., Cha, H., Kim, D., Schperberg, A. V., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.030 · Cited by 154 · see citing works
“Reassuringly, the SL-based prediction accuracy levels are overall higher compared with those obtained by several published transcriptomic-based predictors, including the proliferation index (Whitfield et al., 2006), interferon-g (IFNg) signature (Ayers et al.”
Result
Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN.
Siveke, J., Einwächter, H., Sipos, B., Lubeseder-Martellato, C., Klöppel, G., & Schmid, R. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.002 · Cited by 162 · see citing works
A deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics
Hoang, D.-T., Dinstag, G., Shulman, E. D., Hermida, L. C., Ben-Zvi, D. S., Elis, E., Caley, K., Sammut, S.-J., Sinha, S., Sinha, N., et al. (2024) · Nature Cancer · doi:10.1038/s43018-024-00793-2 · Cited by 157 · see citing works
“54 (proliferation signatures were shown to be prognostic in various cancers, such as breast, kidney and lung cancers); and (3) an epithelial-to-mesenchymal transition (EMT) signature from MSigDB (Molecular Signatures Database) 55 , which is associated with the formation and progression of…”
Background
Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms
Mahoney, J. M., Taroni, J., Martyanov, V., Wood, T. A., Greene, C. S., Pioli, P. A., Hinchcliff, M., & Whitfield, M. L. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004005 · Cited by 153 · see citing works
“The expression of proliferation genes is commonly observed in cancer [2,7,48] and their presence in the gene expression data of SSc was a surprising and unexpected finding [1].”
BackgroundSelf-citation
p53‐repressed miRNAs are involved with E2F in a feed‐forward loop promoting proliferation
Brosh, R., Shalgi, R., Liran, A., Landan, G., Korotayev, K., Nguyen, G. H., Enerly, E., Johnsen, H., Buganim, Y., Solomon, H., et al. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.65 · Cited by 152 · see citing works
“Importantly, the ‘proliferation cluster’ is one of the most prominent expression signatures revealed when tumors are compared to normal tissues or when highly proliferating cells are compared to slow growing cells, and contains many cell-cycle periodic genes (Whitfield et al, 2006).”
Background
The molecular diversity of Luminal A breast tumors
Ciriello, G., Sinha, R., Hoadley, K. A., Skanderup, A. J., Reva, B. A., Perou, C. M., Sander, C., & Schultz, N. D. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2699-3 · Cited by 151 · see citing works
“Most of these genes have also been identified as ‘‘proliferation marker’’ genes [35].”
BackgroundSelf-citation
Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells
Hwang, Y. S., Suzuki, S., Seita, Y., Ito, J., Sakata, Y., Aso, H., Sato, K., Hermann, B. P., & Sasaki, K. (2020) · Nature Communications · doi:10.1038/s41467-020-19350-3 · Cited by 149 · see citing works
A TGFβ-Responsive Gene Signature Is Associated with a Subset of Diffuse Scleroderma with Increased Disease Severity
Sargent, J. L., Milano, A., Bhattacharyya, S., Varga, J., Connolly, M. K., Chang, H. Y., & Whitfield, M. L. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.318 · Cited by 148 · see citing works
“Among the enriched, downregulated GO terms were mitotic cell cycle, cell division, and chromosomal segregation, indicating that TGFb downregulates the proliferation signature (Whitfield et al., 2006) under low-serum conditions.”
BackgroundSelf-citation
MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A
Sun, T., Wang, X., He, H. H., Sweeney, C. J., Liu, S. X., Brown, M. A., Balk, S. P., Lee, G.-S., & Kantoff, P. W. (2013) · Oncogene · doi:10.1038/onc.2013.230 · Cited by 147 · see citing works
The E2F-Regulated Gene Chk1 Is Highly Expressed in Triple-Negative Estrogen Receptor−/Progesterone Receptor−/HER-2− Breast Carcinomas
Verlinden, L., Bempt, I. V., Eelen, G., Drijkoningen, M., Verlinden, I., Kathleen Marchal, D., Wolf‐Peeters, C. D., Christiaens, M.-R., Michiels, L., Bouillon, R., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3545 · Cited by 149 · see citing works
“To this end, a new generation of oncolytic adenoviral vectors, expressing antisense Chk1 cDNA preferentially in tumor cells, has been used in a preclinical setting and yielded promising results (6, 23).”
Background
Exosomes from human adipose‐derived stem cells promote sciatic nerve regeneration via optimizing Schwann cell function
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Authors: Whitfield, M. L., George, L. K., Grant, G. D., & Perou, C. M.
Affiliations: Dartmouth College (US)
University of North Carolina at Chapel Hill (US)
Corresponding author: Whitfield, Michael L.
ORCID: Whitfield, Michael L.
Grant, Gavin D.
Perou, Charles M.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2006-02
Volume: 6
Issue: 2
Pages: 99-106
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc1802
OpenAlex: W2018173663
Cited by: 650
References: 66
Citations by year: 2026: 31 · 2025: 46 · 2024: 35 · 2023: 54 · 2022: 53 · 2021: 54 · 2020: 33 · 2019: 29 · 2018: 22 · 2017: 27 · 2016: 34 · 2015: 15 · 2014: 17 · 2013: 27 · 2012: 26
FWCI: 2.57
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: cell proliferation, proliferation signature, gene expression profiling, tumor markers, cell cycle, carcinogenesis, cancer diagnosis, cancer prognosis
MeSH terms: Cell Cycle, Genetic Markers, Humans, Neoplasms, Prognosis, RNA, Messenger, Biomarkers, Tumor, Gene Expression Profiling, Cell Proliferation

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