Review
Biochemistry & Molecular Biology
Ekenedirichukwu N. Obi, Daniel A. Tellock, Gabriel J. Thomas, Timothy D. Veenstra
Summary: The recent developments in mass spectrometry (MS) have provided new opportunities in biomarker discovery and diagnostics, particularly in analyzing clinical samples at a deeper level. While most developments have focused on blood, there is potential in utilizing archived formalin-fixed paraffin-embedded (FFPE) tissues, which were previously considered difficult to analyze using proteomics techniques. Researchers have developed methods to extract proteins from FFPE tissues, allowing for their analysis using state-of-the-art technologies like MS and protein arrays. This review discusses the history of these developments and their current applications in identifying biomarkers and diagnosing diseases such as cancer.
Article
Chemistry, Analytical
Kenneth Weke, Sachin Kote, Jakub Faktor, Sofian Al Shboul, Naomi Uwugiaren, Paul M. Brennan, David R. Goodlett, Ted R. Hupp, Irena Dapic
Summary: Developments in quantitative proteomics and DIA methodology have enabled protein quantification in biological samples, including formalin-fixed paraffin-embedded (FFPE) tissues. In this study, a simple and precise DIA-MS workflow was established to detect and quantify immune- and glioblastoma (GBM)-relevant proteins in FFPE patient materials. The results showed successful detection and quantification of more than 1700 proteins, including GBM-relevant proteins and immune-related proteins. This strategy has great potential for routine protein quantification in FFPE tissue samples.
ANALYTICA CHIMICA ACTA
(2022)
Article
Medicine, Research & Experimental
Lisa Kreutzer, Peter Weber, Theresa Heider, Mathias Heikenwaelder, Tobias Riedl, Philipp Baumeister, Frederick Klauschen, Claus Belka, Axel Walch, Horst Zitzelsberger, Julia Hess, Kristian Unger
Summary: This study presents a method for simultaneous measurement of the whole exome and the transcriptome from formalin-fixed paraffin-embedded tissue sections. The data demonstrate the feasibility and reproducibility of this approach, expanding the possibilities of multi-omics integration in cancer research.
LABORATORY INVESTIGATION
(2022)
Article
Chemistry, Analytical
Alex Gomez-Gomez, MohammadA Sabbaghi, Noemi Haro, Joan Albanell, Silvia Menendez, Monica Gonzalez, Gabriel Gil-Gomez, Ana Rovira, Oscar J. Pozo
Summary: Formalin-fixed paraffin-embedded (FFPE) tissues are crucial in cancer research, but research on the detection of small molecules in FFPE samples is limited. This study aimed to explore the potential of targeted metabolomics in FFPE specimens and developed a LC-MS/MS method for the quantification of acidic metabolites. The method showed accurate and precise quantification of 40 metabolites in FFPE samples, with implications for cancer research.
Article
Biochemical Research Methods
Cassandra L. Clift, Richard R. Drake, Anand Mehta, Peggi M. Angel
Summary: This study presents a multiplexed imaging mass spectrometry method to spatially localize and selectively access the extracellular matrix on formalin-fixed paraffin-embedded tissue sections. A novel serial enzyme strategy has been developed to define the extracellular matrix, including PTMs, from a single tissue section for MALDI-IMS applications to overcome the challenge of capturing complex ECM peptides.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Andikan J. Nwosu, Santosh A. Misal, Thy Truong, Richard H. Carson, Kei G. Webber, Nathaniel B. Axtell, Yiran Liang, S. Madisyn Johnston, Kenneth L. Virgin, Ethan G. Smith, George Thomas, Terry Morgan, John C. Price, Ryan T. Kelly
Summary: This study modified a sample processing workflow to extract proteins from FFPE tissues and analyze protein expression. By optimizing the extraction conditions, a high-confidence proteome was obtained, and the protein coverage for FFPE tissues reached 88% compared to frozen tissues.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Medicine, Research & Experimental
Bradley L. Ackermann, Ryan D. Morrison, Salisha Hill, Matthew D. Westfall, Brent D. Butts, Michael D. Soper, Jeff A. Fill, Andrew E. Schade, Daniel C. Liebler, Aaron M. Gruver
Summary: MS analysis allows accurate protein quantification from stained paraffin-embedded tissue sections, providing valuable data for the assessment of clinical tissue specimens.
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Hua Zhang, Vamsi Krishna Polavarapu, Pengwei Xing, Miao Zhao, Lucy Mathot, Linxuan Zhao, Gabriela Rosen, Fredrik J. Swartling, Tobias Sjoblom, Xingqi Chen
Summary: Archived FFPE samples are widely used for cancer research, and we developed a highly sensitive method (FFPE-ATAC) to decode chromatin accessibility in FFPE tissues. This method generates high-quality chromatin accessibility profiles and allows analysis of chromatin profiles in regions of interest from a single FFPE tissue section.
Article
Biochemical Research Methods
Pascal Steffen, Jun Li, Jason Chandra, Mahsa S. Ahadi, Anthony J. Gill, Alexander F. Engel, Mark P. Molloy
Summary: Histological risk factors for lymph node metastasis in early-stage colorectal cancers have been described, with molecular features such as effector proteins of epithelial-mesenchymal transition (EMT) showing potential for enhancing metastatic risk assessment. Proteomic and gene expression profiling were used to identify these features, suggesting a link between EMT effectors and locoregional metastasis in T1/T2 CRC. Further development is needed for routine implementation of these findings.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Chemistry, Analytical
Jie Pu, Chao Xue, Shihan Huo, Qingqing Shen, Yang Qu, Xinxin Yang, Bo An, Thomas E. Angel, Zhuo Chen, John T. Mehl, Huaping Tang, Eric Yang, Timothy W. Sikorski, Jun Qu
Summary: This study extensively investigated the challenges of accurate quantification of target proteins in formalin-fixed paraffin-embedded (FFPE) tissues using liquid chromatography-mass spectrometry (LC-MS) and developed a strategy enabling precise quantification. The study demonstrated efficient recovery of target signature peptides from FFPE tissues, indicated that FFPE tissue storage mainly causes decreased immunoreactivity but not chemical degradation of proteins, and proposed a novel calibration approach for accurate quantification. The pipeline was successfully applied to measure the pharmacokinetics of monoclonal antibody (mAb) and its target in FFPE tissues, showing excellent correlation with fresh tissues.
ANALYTICAL CHEMISTRY
(2022)
Article
Biology
Masachika Ikegami, Shinji Kohsaka, Takeshi Hirose, Toshihide Ueno, Satoshi Inoue, Naoki Kanomata, Hideko Yamauchi, Taisuke Mori, Shigeki Sekine, Yoshihiro Inamoto, Yasushi Yatabe, Hiroshi Kobayashi, Sakae Tanaka, Hiroyuki Mano
Summary: The researchers developed MicroSEC, a filtering pipeline to remove sequencing artifacts from archival formalin-fixed and paraffin-embedded samples. The sensitivity and specificity of MicroSEC were confirmed to be 97% and 96% respectively using amplicon-based sequencing with 97 mutations. This tool may improve the reliability of clinical sequencing and advance cancer research using formalin-fixed, paraffin-embedded samples, which are of great interest for genomic analysis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemical Research Methods
Crystal L. Pace, Peggi M. Angel, Richard R. Drake, David C. Muddiman
Summary: N-Linked glycans are structurally diverse polysaccharides that play a significant role in disease progression and cancer. In this study, the first analysis of N-linked glycans in situ by IR-MALDESI MSI was demonstrated, revealing that over 60% of the glycans in the prostate tissue contain sialic acid residues.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Chemistry, Analytical
Yunxia Guo, Junjie Ma, Zhengyue Li, Kaitong Dang, Qinyu Ge, Yan Huang, Guang-zhong Wang, Xiangwei Zhao
Summary: This study investigates the effects of fixation and storage time on the nuclear transcriptome signatures of the brain. The fixation time has a greater impact on the transcriptomic profiles than the retention time of FFPE samples. The findings will guide the preparation of FFPE samples for single-nucleus RNA-seq, especially in transcriptomic studies of brain diseases.
ANALYTICA CHIMICA ACTA
(2023)
Article
Chemistry, Analytical
Rory T. Steven, Marcel Niehaus, Adam J. Taylor, Ammar Nasif, Efstathios Elia, Richard J. A. Goodwin, Zoltan Takats, Josephine Bunch
Summary: Mass spectrometry imaging (MSI) is a powerful technique for providing spatially resolved atomic and molecular information from almost any sample type. Optimizing MSI methods for analysis of FFPE tissue is necessary due to the prevalence and importance of FFPE tissue storage.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Hanan Schoffman, Yishai Levin, Ayelet Itzhaki-Alfia, Lea Tselekovits, Lior Gonen, Gilad Wolf Vainer, Goni Hout-Siloni, Iris Barshack, Zvi R. Cohen, Nevo Margalit, Tal Shahar
Summary: This study compared the effects of formaldehyde-fixed paraffin-embedded (FFPE) tissue blocks and fresh frozen tissue (FFT) on the quantifiable proteome. The results showed that both methods yield a similar number of proteins, but there are significant differences in the proteome composition, with FFPE specimens enriched with smaller proteins.
Article
Oncology
Yang Liu, Nilay S. Sethi, Toshinori Hinoue, Barbara G. Schneider, Andrew D. Cherniack, Francisco Sanchez-Vega, Jose A. Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, Jaegil Kim, Walid Chatila, Rehan Akbani, Rupa S. Kanchi, Charles S. Rabkin, Joseph E. Willis, Kenneth K. Wang, Shannon J. McCall, Lopa Mishra, Akinyemi I. Ojesina, Susan Bullman, Chandra Sekhar Pedamallu, Alexander J. Lazar, Ryo Sakai, Vesteinn Thorsson, Adam J. Bass, Peter W. Laird
Article
Biochemistry & Molecular Biology
Matthew H. Bailey, Collin Tokheim, Eduard Porta-Pardo, Sohini Sengupta, Denis Bertrand, Amila Weerasinghe, Antonio Colaprico, Michael C. Wendl, Jaegil Kim, Brendan Reardon, Patrick Kwok-Shing Ng, Kang Jin Jeong, Song Cao, Zixing Wang, Jianjiong Gao, Qingsong Gao, Fang Wang, Eric Minwei Liu, Loris Mularoni, Carlota Rubio-Perez, Niranjan Nagarajan, Isidro Cortes-Ciriano, Daniel Cui Zhou, Wen-Wei Liang, Julian M. Hess, Venkata D. Yellapantula, David Tamborero, Abel Gonzalez-Perez, Chayaporn Suphavilai, Jia Yu Ko, Ekta Khurana, Peter J. Park, Eliezer M. Van Allen, Han Liang, Michael S. Lawrence, Adam Godzik, Nuria Lopez-Bigas, Josh Stuart, David Wheeler, Gad Getz, Ken Chen, Alexander J. Lazar, Gordon B. Mills, Rachel Karchin, Li Ding
Article
Biochemistry & Molecular Biology
Kuan-lin Huang, R. Jay Mashl, Yige Wu, Deborah I. Ritter, Jiayin Wang, Clara Oh, Marta Paczkowska, Sheila Reynolds, Matthew A. Wyczalkowski, Ninad Oak, Adam D. Scott, Michal Krassowski, Andrew D. Cherniack, Kathleen E. Houlahan, Reyka Jayasinghe, Liang-Bo Wang, Daniel Cui Zhou, Di Liu, Song Cao, Young Won Kim, Amanda Koire, Joshua F. McMichael, Vishwanathan Hucthagowder, Tae-Beom Kim, Abigail Hahn, Chen Wang, Michael D. McLellan, Fahd Al-Mulla, Kimberly J. Johnson, Olivier Lichtarge, Paul C. Boutros, Benjamin Raphael, Alexander J. Lazar, Wei Zhang, Michael C. Wendl, Ramaswamy Govindan, Sanjay Jain, David Wheeler, Shashikant Kulkarni, John F. Dipersio, Juri Reimand, Funda Meric-Bernstam, Ken Chen, Ilya Shmulevich, Sharon E. Plon, Feng Chen, Li Ding
Article
Biochemistry & Molecular Biology
Francisco Sanchez-Vega, Marco Mina, Joshua Armenia, Walid K. Chatila, Augustin Luna, Konnor C. La, Sofia Dimitriadoy, David L. Liu, Havish S. Kantheti, Sadegh Saghafinia, Debyani Chakravarty, Foysal Daian, Qingsong Gao, Matthew H. Bailey, Wen-Wei Liang, Steven M. Foltz, Ilya Shmulevich, Li Ding, Zachary Heins, Angelica Ochoa, Benjamin Gross, Jianjiong Gao, Hongxin Zhang, Ritika Kundra, Cyriac Kandoth, Istemi Bahceci, Leonard Dervishi, Ugur Dogrusoz, Wanding Zhou, Hui Shen, Peter W. Laird, Gregory P. Way, Casey S. Greene, Han Liang, Yonghong Xiao, Chen Wang, Antonio Iavarone, Alice H. Berger, Trever G. Bivona, Alexander J. Lazar, Gary D. Hammer, Thomas Giordano, Lawrence N. Kwong, Grant McArthur, Chenfei Huang, Aaron D. Tward, Mitchell J. Frederick, Frank McCormick, Matthew Meyerson, Eliezer M. Van Allen, Andrew D. Cherniack, Giovanni Ciriello, Chris Sander, Nikolaus Schultz
Article
Biochemistry & Molecular Biology
Katherine A. Hoadley, Christina Yau, Toshinori Hinoue, Denise M. Wolf, Alexander J. Lazar, Esther Drill, Ronglai Shen, Alison M. Taylor, Andrew D. Cherniack, Vesteinn Thorsson, Rehan Akbani, Reanne Bowlby, Christopher K. Wong, Maciej Wiznerowicz, Francisco Sanchez-Vega, A. Gordon Robertson, Barbara G. Schneider, Michael S. Lawrence, Houtan Noushmehr, Tathiane M. Malta, Joshua M. Stuart, Christopher C. Benz, Peter W. Laird
Article
Biochemistry & Molecular Biology
Tathiane M. Malta, Artem Sokolov, Andrew J. Gentles, Tomasz Burzykowski, Laila Poisson, John N. Weinstein, Bozena Kaminska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwinska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, Alex Krasnitz, Andrew K. Godwin, Alexander J. Lazar, Joshua M. Stuart, Katherine A. Hoadley, Peter W. Laird, Houtan Noushmehr, Maciej Wiznerowicz
Article
Immunology
Vesteinn Thorsson, David L. Gibbs, Scott D. Brown, Denise Wolf, Dante S. Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F. Gao, Christopher L. Plaisier, James A. Eddy, Elad Ziv, Aedin C. Culhane, Evan O. Paull, I. K. Ashok Sivakumar, Andrew J. Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S. Parker, Lisle E. Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M. Reynolds, Reanne Bowlby, Andrea Califano, Andrew D. Cherniack, Dimitris Anastassiou, Davide Bedognetti, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M. Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I. Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K. Choueiri, John N. Weinstein, Justin Guinney, Joel Saltz, Robert A. Holt, Charles E. Rabkin, Alexander J. Lazar, Jonathan S. Serody, Elizabeth G. Demicco, Mary L. Disis, Benjamin G. Vincent, Llya Shmulevich
Article
Cell Biology
Michael Seiler, Shouyong Peng, Anant A. Agrawal, James Palacino, Teng Teng, Ping Zhu, Peter G. Smith, Silvia Buonamici, Lihua Yu
Article
Cell Biology
Reyka G. Jayasinghe, Song Cao, Qingsong Gao, Michael C. Wendl, Nam Sy Vo, Sheila M. Reynolds, Yanyan Zhao, Hector Climente-Gonzalez, Shengjie Chai, Fang Wang, Rajees Varghese, Mo Huang, Wen-Wei Liang, Matthew A. Wyczalkowski, Sohini Sengupta, Zhi Li, Samuel H. Payne, David Fenyo, Jeffrey H. Miner, Matthew J. Walter, Benjamin Vincent, Eduardo Eyras, Ken Chen, Ilya Shmulevich, Feng Chen, Li Ding
Article
Cell Biology
Qingsong Gao, Wen-Wei Liang, Steven M. Foltz, Gnanavel Mutharasu, Reyka G. Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M. Reynolds, Matthew A. Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q. Sun, Ken Chen, Alexander J. Lazar, Ryan C. Fields, Michael C. Wendl, Brian A. Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding
Article
Cell Biology
Christopher J. Ricketts, Aguirre A. de Cubas, Huihui Fan, Christof C. Smith, Martin Lang, Ed Reznik, Reanne Bowlby, Ewan A. Gibb, Rehan Akbani, Rameen Beroukhim, Donald P. Bottaro, Toni K. Choueiri, Richard A. Gibbs, Andrew K. Godwin, Scott Haake, A. Ari Hakimi, Elizabeth P. Henske, James J. Hsieh, Thai H. Ho, Rupa S. Kanchi, Bhavani Krishnan, David J. Kwaitkowski, Wembin Lui, Maria J. Merino, Gordon B. Mills, Jerome Myers, Michael L. Nickerson, Victor E. Reuter, Laura S. Schmidt, C. Simon Shelley, Hui Shen, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Benjamin G. Vincent, Cathy D. Vocke, David A. Wheeler, Lixing Yang, William T. Kim, A. Gordon Robertson, Paul T. Spellman, W. Kimryn Rathmell, W. Marston Linehan
Article
Oncology
Andre Kahles, Kjong-Van Lehmann, Nora C. Toussaint, Matthias Huser, Stefan G. Stark, Timo Sachsenberg, Oliver Stegle, Oliver Kohlbacher, Chris Sander, Gunnar Ratsch
Article
Biochemistry & Molecular Biology
Anil Korkut, Sobia Zaidi, Rupa S. Kanchi, Shuyun Rao, Nancy R. Gough, Andre Schultz, Xubin Li, Philip L. Lorenzi, Ashton C. Berger, Gordon Robertson, Lawrence N. Kwong, Mike Datto, Jason Roszik, Shiyun Ling, Visweswaran Ravikumar, Ganiraju Manyam, Arvind Rao, Simon Shelley, Yuexin Liu, Zhenlin Ju, Donna Hansel, Guillermo de Velasco, Arjun Pennathur, Jesper B. Andersen, Colm J. O'Rourke, Kazufumi Ohshiro, Wilma Jogunoori, Bao-Ngoc Nguyen, Shulin Li, Hatice U. Osmanbeyoglu, Jaffer A. Ajani, Sendurai A. Mani, Andres Houseman, Maciej Wiznerowicz, Jian Chen, Shoujun Gu, Wencai Ma, Jiexin Zhang, Pan Tong, Andrew D. Cherniack, Chuxia Deng, Linda Resar, John N. Weinstein, Lopa Mishra, Rehan Akbani
Article
Cell Biology
Yumeng Wang, Xiaoyan Xu, Dejan Maglic, Michael T. Dill, Kamalika Mojumdar, Patrick Kwok-Shing Ng, Kang Jin Jeong, Yiu Huen Tsang, Daniela Moreno, Venkata Hemanjani Bhavana, Xinxin Peng, Zhongqi Ge, Hu Chen, Jun Li, Zhongyuan Chen, Huiwen Zhang, Leng Han, Di Du, Chad J. Creighton, Gordon B. Mills, Fernando Camargo, Han Liang
Correction
Immunology
Vesteinn Thorsson, David L. Gibbs, Scott D. Brown, Denise Wolf, Dante S. Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F. Gao, Christopher L. Plaisier, James A. Eddy, Elad Ziv, Aedin C. Culhane, Evan O. Paull, I. K. Ashok Sivakumar, Andrew J. Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S. Parker, Lisle E. Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M. Reynolds, Reanne Bowlby, Andrea Califano, Andrew D. Cherniack, Dimitris Anastassiou, Davide Bedognetti, Younes Mokrab, Aaron M. Newman, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M. Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I. Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K. Choueiri, John N. Weinstein, Justin Guinney, Joel Saltz, Robert A. Holt, Charles S. Rabkin, Alexander J. Lazar, Jonathan S. Serody, Elizabeth G. Demicco, Mary L. Disis, Benjamin G. Vincent, Ilya Shmulevich