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
Endocrinology & Metabolism
Norifusa Iwahashi, Hironobu Umakoshi, Masatoshi Ogata, Tazuru Fukumoto, Hiroki Kaneko, Eriko Terada, Shunsuke Katsuhara, Naohiro Uchida, Katsuhiko Sasaki, Maki Yokomoto-Umakoshi, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Ogawa
Summary: This study evaluated the utility of transcriptome data from formalin-fixed paraffin-embedded (FFPE) samples in adrenocortical tumor research. The results demonstrated that FFPE samples can serve as a reliable alternative to fresh frozen samples for whole transcriptome profiling of adrenocortical tumors, enabling distinction of tumor types and detection of marker genes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
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
Biochemistry & Molecular Biology
Linxuan Zhao, Pengwei Xing, Vamsi Krishna Polavarapu, Miao Zhao, Blanca Valero-Martinez, Yonglong Dang, Nagaprathyusha Maturi, Lucy Mathot, Ines Neves, Irem Yildirim, Fredrik Johansson Swartling, Tobias Sjoblom, Lene Uhrbom, Xingqi Chen
Summary: The study introduces a new method (FACT-seq) for efficient analysis of histone modifications in archived FFPE tissues, significantly improving resolution. High-quality chromatin profiles can be generated using a small number of FFPE nuclei, offering insights into epigenetic regulation in cancer and human disease.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Allison K. Miller, Cara L. Brosnahan, Anjali Pande, Cindy F. Baker, Jemma L. Geoghegan, Jane Kitson, Neil J. Gemmell, Edwina J. Dowle
Summary: Infectious diseases have a significant impact on various organisms, and understanding the interactions between hosts and pathogens is crucial for their conservation and management. The use of genomic approaches has made it easier to obtain this knowledge quickly, however, many species still face challenges in accessing appropriate samples and data. Archival materials, such as formalin-fixed paraffin-embedded tissue samples, may provide a valuable resource for studying pathogen emergence and host responses over long periods of time.
MOLECULAR ECOLOGY RESOURCES
(2023)
Article
Multidisciplinary Sciences
Shirong Zhang, Shutao He, Xin Zhu, Yunfei Wang, Qionghuan Xie, Xianrang Song, Chunwei Xu, Wenxian Wang, Ligang Xing, Chengqing Xia, Qian Wang, Wenfeng Li, Xiaochen Zhang, Jinming Yu, Shenglin Ma, Jiantao Shi, Hongcang Gu
Summary: The authors developed a DNA methylation profiling assay and a machine learning classifier to predict the origin of metastatic tumours in CUP patients using formalin-fixed, paraffin embedded samples.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dymph Klay, Karin M. Kazemier, Joanne J. van der Vis, Hidde M. Smits, Jan C. Grutters, Coline H. M. van Moorsel
Summary: This study found differences between sporadic idiopathic pulmonary fibrosis, telomere mutation-induced pulmonary fibrosis, and surfactant related gene mutation-induced pulmonary fibrosis, as well as a significant association between high expression of a high number of endoplasmic reticulum stress genes and shorter survival time.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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)
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
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
Chemistry, Analytical
Hao Chen, Yuefei Zhang, Haichao Zhou, Weiran Chen, Jiayi Peng, Yang Feng, Linyuan Fan, Jun Li, Jin Zi, Yan Ren, Qidan Li, Siqi Liu
Summary: Spatial proteomics plays an important role in the era of single-cell biology. In this study, a new routine workflow was developed for proteomic analysis of micro-FFPE tissues, allowing the construction of a spatial proteomic atlas of mouse brain, which exhibited typical characteristics of spatial-dependent protein abundance and functional enrichment.
ANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Liang Zong, Yabing Zhu, Yuan Jiang, Ying Xia, Qun Liu, Sanjie Jiang
Summary: RNA-Seq analysis of FFPE samples is a highly effective approach but degradation of RNAs limits its application. A new RNA-Seq method has been developed to overcome this limitation. This study compares and evaluates three commercially available exome capture kits, providing valuable guidance for obtaining high-quality data from FFPE samples.
Article
Medicine, General & Internal
Irene Y. Chong, Naureen Starling, Alistair Rust, John Alexander, Lauren Aronson, Marta Llorca-Cardenosa, Ritika Chauhan, Asif Chaudry, Sacheen Kumar, Kerry Fenwick, Ioannis Assiotis, Nik Matthews, Ruwaida Begum, Andrew Wotherspoon, Monica Terlizzo, David Watkins, Ian Chau, Christopher J. Lord, Syed Haider, Sheela Rao, David Cunningham
Summary: The application of massively parallel sequencing in gastro-oesophageal cancer has led to the identification of aberrant druggable pathways and somatic mutations within relevant genes. Exome sequencing data from archival FFPE samples showed high mutational concordance with fresh-frozen samples, but FFPE samples tended to have higher mutant-allele heterogeneity scores.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Alessandra Borgognone, Garazi Serna, Marc Noguera-Julian, Lidia Alonso, Mariona Parera, Francesc Catala-Moll, Lidia Sanchez, Roberta Fasani, Roger Paredes, Paolo Nuciforo
Summary: The comparison of fresh-frozen (FF) and FFPE colorectal cancer (CRC) tissues revealed differences in microbial diversity and composition, with FF samples enriched in representative CRC-associated bacteria and FFPE samples mainly enriched in typical contaminants. An internal quality index showed a correlation between the similarity within sample pairs and the dominance of contaminant taxa. These findings may provide useful indications for accurate and reproducible metagenomics analyses, especially in larger studies in human cancer genomics using FFPE specimens.
Article
Medical Laboratory Technology
Feng-Ming Hsu, Yih-Leong Chang, Chung-Yung Chen, Shu-Rung Lin, Jason Chia-Hsien Cheng
Summary: HPR is an alternative RNA profiling approach with high sensitivity, reproducibility, robustness, and capability for molecular diagnostics in FFPE tumor biopsy specimens of lung and esophageal cancer.
CLINICAL CHEMISTRY
(2023)
Review
Oncology
Nafie F. Makady, David Ramzy, Ramy Ghaly, Raafat R. Abdel-Malek, Kyrillus S. Shohdy
Summary: A systematic review of plasmablastic lymphoma showed a significant association between aggressive chemotherapy and better overall survival. Factors like stage, viral status, and site involvement were found to be related to overall survival outcomes.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Oncology
Vincenza Conteduca, Sheng-Yu Ku, Luisa Fernandez, Angel Dago-Rodriquez, Jerry Lee, Adam Jendrisak, Megan Slade, Cole Gilbertson, Jyothi Manohar, Michael Sigouros, Yipeng Wang, Ryan Dittamore, Rick Wenstrup, Juan Miguel Mosquera, Joseph D. Schonhoft, Himisha Beltran
Summary: Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that often involves the combined loss of tumor suppressor genes like RB1, TP53, and PTEN. It is believed to arise from a trans-differentiation process from a precursor prostate adenocarcinoma during treatment resistance. Single-cell genomic analysis and phenotypic evaluation of cellular diversity can provide insights into tumor heterogeneity in advanced prostate cancer patients.
NPJ PRECISION ONCOLOGY
(2021)
Correction
Oncology
Vincenza Conteduca, Sheng-Yu Ku, Luisa Fernandez, Angel Dago-Rodriquez, Jerry Lee, Adam Jendrisak, Megan Slade, Cole Gilbertson, Jyothi Manohar, Michael Sigouros, Yipeng Wang, Ryan Dittamore, Rick Wenstrup, Juan Miguel Mosquera, Joseph D. Schonhoft, Himisha Beltran
NPJ PRECISION ONCOLOGY
(2021)
Article
Medicine, General & Internal
Ahmed O. Elmehrath, Ahmed M. Afifi, Muneer J. Al-Husseini, Anas M. Saad, Nathaniel Wilson, Kyrillus S. Shohdy, Patrick Pilie, Mohamad Bassam Sonbol, Omar Alhalabi
Summary: This retrospective cohort study analyzed the causes of death among US patients with metastatic prostate cancer from 2000 to 2016. Noncancer causes, such as cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases, were found to be significant contributors to mortality among these patients.
Article
Biology
Ada Gjyrezi, Giuseppe Galletti, Jiaren Zhang, Daniel Worroll, Michael Sigouros, Seaho Kim, Victoria Cooley, Karla Ballman, Allyson J. Ocean, Manish A. Shah, Joseph M. Scandura, Andrea Sboner, David M. Nanus, Himisha Beltran, Scott Tagawa, Paraskevi Giannakakou
Summary: Ada Gjyrezi et al. demonstrate that ddPCR is capable of accurately measuring the expression levels of androgen receptor variants (AR-Vs) in individual circulating tumor cells (CTCs) from prostate cancer patients. They reveal that current CTC isolation methods may underestimate the prevalence of AR-Vs, and highlight the potential of a specific variant, AR-v567es, as a biomarker for an aggressive subtype of prostate cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Kyrillus S. Shohdy, Dario M. Villamar, Yen Cao, Janson Trieu, Kristin S. Price, Rebecca Nagy, Scott T. Tagawa, Ana M. Molina, Cora N. Sternberg, David M. Nanus, Juan Miguel Mosquera, Olivier Elemento, Guru P. Sonpavde, Petros Grivas, Nicholas J. Vogelzang, Bishoy Morris Faltas
Summary: This study demonstrates that targeted sequencing of ctDNA can predict disease progression and clinical outcomes in patients with advanced urothelial carcinoma. Combination of ctDNA-derived metrics and clinical factors improves prognostic models. Dynamic monitoring of serial ctDNA enables precision medicine guidance.
BRITISH JOURNAL OF CANCER
(2022)
Article
Medicine, General & Internal
Matthew Brendel, Vanesa Getseva, Majd Al Assaad, Michael Sigouros, Alexandros Sigaras, Troy Kane, Pegah Khosravi, Juan Miguel Mosquera, Olivier Elemento, Iman Hajirasouliha
Summary: In this study, a weakly-supervised purity (wsPurity) approach was proposed to accurately quantify tumor purity within a digitally captured histological slide. The model demonstrated high accuracy in predicting cancer type and showed promising generalizability to unseen data from an external cohort. The approach also identified high resolution tumor regions within a slide and could stratify tumors into high and low purity.
Review
Biotechnology & Applied Microbiology
Hamdy A. Azim, Kyrillus S. Shohdy, Hagar Elghazawy, Monica M. Salib, Doaa Almeldin, Loay Kassem
Summary: This study analyzed data from 19 studies involving 2403 patients with non-metastatic TNBC, showing that PD-L1 positivity is associated with higher pCR rates and better DFS and OS outcomes. Transcriptomic data further suggested that PD-L1 expression is indicative of upregulated immune-related genes that mediate chemotherapy response in TNBC.
Review
Oncology
Kathryn Owen, Ramy Ghaly, Kyrillus S. Shohdy, Fiona Thistlethwaite
Summary: Background TCR-T therapy has shown promise in solid tumors, but there is limited evidence on the optimal LD regimen. This systematic review analyzed 19 clinical trials and found that cyclophosphamide and fludarabine were the most common LD regimen, but safety data were lacking.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Bhavneet Bhinder, Alison Ferguson, Michael Sigouros, Manik Uppal, Ahmed G. Elsaeed, Rohan Bareja, Hussein Alnajar, Kenneth Wha Eng, Vincenza Conteduca, Andrea Sboner, Juan Miguel Mosquera, Olivier Elemento, Himisha Beltran
Summary: This study analyzed the RNA-sequencing and whole-exome sequencing data of 170 patients with neuroendocrine prostate cancer (NEPC). It found that NEPC has a unique tumor immune landscape compared to other prostate cancer types and small-cell lung cancer (SCLC). NEPC is characterized by a relatively immune-depleted tumor immune microenvironment and less mutations, but has comparable expression of checkpoint genes PD-L1 and CTLA-4 with SCLC. These findings can inform the development of immunotherapy strategies for NEPC.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Takayuki Sumiyoshi, Xiaofei Wang, Evan W. Warner, Andrea Sboner, Matti Annala, Michael Sigouros, Kevin Beja, Kei Mizuno, Shengyu Ku, Ladan Fazli, James Eastham, Mary-Ellen Taplin, Jeffrey Simko, Susan Halabi, Michael J. Morris, Martin E. Gleave, Alexander W. Wyatt, Himisha Beltran
Summary: This study analyzed the molecular features of post-treated tumors in high-risk localized prostate cancer patients who received neoadjuvant chemohormonal therapy, revealing that lower tumor fraction after chemohormonal therapy was associated with poor outcomes, while TP53 alterations and high cell cycle transcriptomic activity were linked to aggressive residual disease.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Francesca Khani, William F. Hooper, Xiaofei Wang, Timothy R. Chu, Minita Shah, Lara Winterkorn, Michael Sigouros, Vincenza Conteduca, David Pisapia, Sara Wobker, Sydney Walker, Julie N. Graff, Brian Robinson, Juan Miguel Mosquera, Andrea Sboner, Olivier Elemento, Nicolas Robine, Himisha Beltran
Summary: In this study, the clinical and molecular characteristics of intracranial metastases in prostate cancer were evaluated. Whole genome sequencing was performed to identify genomic alterations. The results revealed a higher diversity of structural alterations in intracranial metastases compared to primary tumors, with AR and TP53 alterations being frequently observed. Clonality analysis provided insights into the genomic factors contributing to metastatic spread in prostate cancer.
NPJ PRECISION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Francesco Orlando, Alessandro Romanel, Blanca Trujillo, Michael Sigouros, Daniel Wetterskog, Orsetta Quaini, Gianmarco Leone, Jenny Z. Xiang, Anna Wingate, Scott Tagawa, Anuradha Jayaram, Mark Linch, Mariam Jamal-Hanjani, Charles Swanton, Mark A. Rubin, Alexander W. Wyatt, Himisha Beltran, Gerhardt Attard, Francesca Demichelis
Summary: Sequencing of cell-free DNA in cancer patients' plasma can detect tumor cell genomic alterations and aid clinical decision-making. The novel detection strategy, PCF SELECT, shows improved detection of genomic alterations in samples with low tumor fractions. More extensive pan-genome allelic imbalance was identified in plasma samples from prostate cancer patients.