Article
Biotechnology & Applied Microbiology
Qiuying Ding, Zhengping Hou, Zhibo Zhao, Yao Chen, Lei Zhao, Yue Xiang
Summary: In this study, a prognostic signature reflecting genomic instability and overall survival (OS) of colorectal cancer (CRC) patients was constructed by analyzing splicing profiles, somatic mutations, and other related information. This signature showed good predictive performance for OS and could be used for clinical stratification and prognosis prediction. The study also identified splicing factors associated with OS and verified their roles in cell proliferation and migration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Xuyan Liu, Xiaomeng Shi, Qing Xin, Zhiying Liu, Fengjiao Pan, Dan Qiao, Mengke Chen, Yiyin Zhang, Wencong Guo, Changying Li, Yan Zhang, Leping Shao, Ruixiao Zhang
Summary: This study investigated the effect of PKD1 and PKD2 variants on exon splicing and found that 11 variants interfere with normal splicing, affecting the function of ADPKD-associated genes.
Article
Biochemistry & Molecular Biology
Olivia M. Marx, Marc M. Mankarious, Melanie A. Eshelman, Wei Ding, Walter A. Koltun, Gregory S. Yochum
Summary: Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC) has steadily increased. The understanding of genetic and molecular basis of EOCRC is limited. This study identified increased expression of c-MYC proto-oncogene (MYC) and its downstream targets in tumor samples. Elevated expression of the PVT1 long-non-coding RNA (lncRNA) was also detected. The findings suggest that deregulated MYC contributes to CRCs in younger patients.
Article
Biochemistry & Molecular Biology
Lirong Hu, Abdul Sammad, Congcong Zhang, Luiz F. Brito, Qing Xu, Yachun Wang
Summary: This study evaluated the changes in milk yield, physiological indicators, blood biochemical parameters, and alternative splicing patterns in lactating Holstein cows under heat stress conditions. The results showed that heat stress negatively impacted various biological processes of Holstein cows. Additionally, heat stress increased the occurrence of alternative splicing events, with genes involved in mRNA splicing, immune, and metabolic processes being enriched. Two candidate genes associated with heat stress responses in dairy cows were identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Narumi Sakaguchi, Mikita Suyama
Summary: Causative mutations for genetic disorders have been mainly identified in exonic regions, but recent research shows mutations in deep intronic regions can also cause disorders through pseudo-exon activation. In normal individuals, an average of 2.6 pseudo-exon activation events were found, more at the 5' donor splice sites. This suggests that pseudo-exon activation events can be observed in normal individuals at a certain frequency.
Article
Oncology
Liam F. Spurr, Carlos A. Martinez, Rohan R. Katipally, Soumya C. Iyer, Sian A. Pugh, John A. Bridgewater, John N. Primrose, Enric Domingo, Timothy S. Maughan, Michael D'Angelica, Mark Talamonti, Mitchell C. Posner, Philip P. Connell, Ralph R. Weichselbaum, Sean P. Pitroda
Summary: Personalized treatment approaches are crucial for patients with limited liver metastases from colorectal cancer. A study involving three large cohorts found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases. However, high CIN70 scores also create a therapeutic vulnerability to DNA-damaging therapies, leading to improved treatment responses. CIN70 could potentially serve as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Zijing Lin, Jianping Gong, Guochao Zhong, Jiejun Hu, Dong Cai, Lei Zhao, Zhibo Zhao
Summary: This study investigated the relationship between alternative splicing events and cholangiocarcinoma, constructing a prognostic signature with six AS events. The research identified CDK11A as a negative regulator of survival-associated AS events and found that patients with high AS risk score may benefit more from immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Agronomy
Yingxue Yang, Chao Zhang, De Zhu, Huiying He, Zhaoran Wei, Qiaoling Yuan, Xiaoxia Li, Xu Gao, Bin Zhang, Hongsheng Gao, Bo Wang, Shuaimin Cao, Tianyi Wang, Yuhua Li, Xiaoman Yu, Longbiao Guo, Guanjing Hu, Qian Qian, Lianguang Shang
Summary: This study aims to identify candidate genes and characterize their response patterns during rice adaptation to high temperatures at the seedling stage. Comparison of transcript abundances revealed differentially expressed genes between heat-sensitive and heat-tolerant rice pools under heat stress. Alternative splicing events and gene expression patterns associated with heat stress were also identified. These findings provide valuable insights into the regulatory mechanisms of rice response to heat stress and offer potential targets for breeding heat-tolerant rice varieties.
Article
Oncology
Sophia J. Wagner, Daniel Reisenbuechler, Nicholas P. West, Jan Moritz Niehues, Jiefu Zhu, Sebastian Foersch, Gregory Patrick Veldhuizen, Philip Quirke, Heike I. Grabsch, Piet A. van den Brandt, Gordon G. A. Hutchins, Susan D. Richman, Tanwei Yuan, Rupert Langer, Josien C. A. Jenniskens, Kelly Offermans, Wolfram Mueller, Richard Gray, Stephen B. Gruber, Joel K. Greenson, Gad Rennert, Joseph D. Bonner, Daniel Schmolze, Jitendra Jonnagaddala, Nicholas J. Hawkins, Robyn L. Ward, Dion Morton, Matthew Seymour, Laura Magill, Marta Nowak, Jennifer Hay, Viktor H. Koelzer, David N. Church, Christian Matek, Carol Geppert, Chaolong Peng, Cheng Zhi, Xiaoming Ouyang, Jacqueline A. James, Maurice B. Loughrey, Manuel Salto-Tellez, Hermann Brenner, Michael Hoffmeister, Daniel Truhn, Julia A. Schnabel, Melanie Boxberg, Tingying Peng, Jakob Nikolas Kather
Summary: This study develops a new transformer-based pipeline for predicting prognostic biomarkers from colorectal cancer pathology slides. The results show that this approach significantly improves performance, generalizability, data efficiency, and interpretability compared to current algorithms. The method also solves a longstanding diagnostic problem by achieving clinical-grade performance on endoscopic biopsy tissue.
Article
Biochemistry & Molecular Biology
Ling Liu, Urmi Das, Samuel Ogunsola, Jiuyong Xie
Summary: This study focuses on the pairing of splice sites across introns or exons in rat GH3 pituitary cells, revealing correlations between RISE indexes at specific introns or exons and inversely correlated with adjacent exons usage. The modulation of paired indexes by depolarization and disruptible by 5-aza-Cytidine was also observed. The nucleotide matrices of RISE-positive splice sites deviated significantly from rat consensus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Mo-Xian Chen, Chong-Chong Lu, Peng-Cheng Sun, Yong-Xin Nie, Yuan Tian, Qi-Juan Hu, Debatosh Das, Xuan-Xuan Hou, Bei Gao, Xi Chen, Shou-Xu Liu, Cheng-Chao Zheng, Xiang-Yu Zhao, Lei Dai, Jianhua Zhang, Ying-Gao Liu
Summary: The study found that isolated maize embryos were able to germinate under high salt conditions, while intact seeds were highly repressed. The results suggest that maize endosperm might play a role in transducing salt stress signals to surrounding tissues such as embryos. Additionally, the study showed that there are substantial differences in post-transcriptional and translational changes between salt-treated embryos and endosperm during maize seed germination.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Plant Sciences
G. Ramakrishna, Parampreet Kaur, Anupam Singh, Sunishtha S. Yadav, Sandhya Sharma, N. K. Singh, Kishor Gaikwad
Summary: Comparative transcriptome analyses revealed high variability in heat stress response among Cajanus species, with Cajanus scarabaeoides being the most thermotolerant. The study provides important insights into the molecular mechanisms responsible for heat stress tolerance in pigeonpea and lays the foundation for the identification of candidate genes for the development of thermo-tolerant pigeonpea cultivars.
PLANT CELL REPORTS
(2021)
Review
Biotechnology & Applied Microbiology
Jinkai Wang
Summary: Post-transcriptional processing of RNAs is regulated by RNA binding proteins and transcription factors, as well as histone modifications. High-throughput sequencing techniques have allowed for the study of these processes using multiomics data, but deciphering the fundamental regulatory roles of these processes remains a challenge. This review discusses the regulatory mechanisms of post-transcriptional processes and outlines general principles and approaches for dissecting these mechanisms through integration of multiomics data and public resources.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2021)
Review
Biochemistry & Molecular Biology
Natalia N. Singh, Collin A. O'Leary, Taylor Eich, Walter N. Moss, Ravindra N. Singh
Summary: This article reviews the structural context of exonic and intronic cis-elements that promote or prevent exon 7 recognition in SMN genes. It discusses how structural rearrangements triggered by single nucleotide substitutions can bring drastic changes in SMN2 exon 7 splicing. Potential mechanisms by which inter-intronic structures might impact splicing outcomes are also proposed.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Oncology
Marta Manco, Ugo Ala, Daniela Cantarella, Emanuela Tolosano, Enzo Medico, Fiorella Altruda, Sharmila Fagoonee
Summary: RNA binding protein ESRP1 can drive tumor progression in colorectal cancer cells by upregulating RAC1b expression, providing potential therapeutic targets for cases with high ESRP1 expression.
Article
Oncology
Bjornar T. B. Flatin, Hege Marie Vedeld, Rita Pinto, Jonas Langerud, Guro E. Lind, Ragnhild A. Lothe, Anita Sveen, Marine Jeanmougin
Summary: Intratumor heterogeneity of colorectal cancers (CRCs) is mainly reflected in the genomic and epigenomic levels. Our study revealed that CIMP status in primary CRCs is consistent, although spatial discrepancies in individual genes indicate the potential of large-scale analysis of multiregional samples to identify robust CIMP markers for intratumor heterogeneity.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
John Pluta, Louise C. Pyle, Kevin T. Nead, Rona Wilf, Mingyao Li, Nandita Mitra, Benita Weathers, Kurt D'Andrea, Kristian Almstrup, Lynn Anson-Cartwright, Javier Benitez, Christopher D. Brown, Stephen Chanock, Chu Chen, Victoria K. Cortessis, Alberto Ferlin, Carlo Foresta, Marija Gamulin, Jourik A. Gietema, Chiara Grasso, Mark H. Greene, Tom Grotmol, Robert J. Hamilton, Trine B. Haugen, Russ Hauser, Michelle A. T. Hildebrandt, Matthew E. Johnson, Robert Karlsson, Lambertus A. Kiemeney, Davor Lessel, Ragnhild A. Lothe, Jennifer T. Loud, Chey Loveday, Paloma Martin-Gimeno, Coby Meijer, Jeremie Nsengimana, David I. Quinn, Thorunn Rafnar, Shweta Ramdas, Lorenzo Richiardi, Rolf I. Skotheim, Kari Stefansson, Clare Turnbull, David J. Vaughn, Fredrik Wiklund, Xifeng Wu, Daphne Yang, Tongzhang Zheng, Andrew D. Wells, Struan F. A. Grant, Ewa Rajpert-De Meyts, Stephen M. Schwartz, D. Timothy Bishop, Katherine A. McGlynn, Peter A. Kanetsky, Katherine L. Nathanson
Summary: Testicular germ cell tumors are highly heritable, and a large genome association study identified 22 novel loci, some of which may assist screening and treatment decisions through the study of PRS, reducing the risks in survivors. These findings highlight the interconnected nature of two known pathways that promote TGCT susceptibility, and implicate an additional biological pathway.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Anita Sveen, Bjarne Johannessen, Ina A. Eilertsen, Bard Rosok, Marie Gulla, Peter W. Eide, Jarle Bruun, Kushtrim Kryeziu, Leonardo A. Meza-Zepeda, Ola Myklebost, Bjorn A. Bjornbeth, Rolf Skotheim, Arild Nesbakken, Ragnhild A. Lothe
Summary: Only a subset of mutations in microsatellite stable colorectal cancers were expressed, and the expressed mutation dose may provide an opportunity for more fine-tuned biomarker interpretations.
Article
Oncology
Susanne G. Kidd, Kristina T. Carm, Mari Bogaard, Linn Guro Olsen, Anne Cathrine Bakken, Marthe Lovf, Ragnhild A. Lothe, Karol Axcrona, Ulrika Axcrona, Rolf I. Skotheim
Summary: In primary prostate cancer, high expression of SCHLAP1 serves as a robust prognostic biomarker for predicting biochemical recurrence and is associated with adverse clinicopathological characteristics. The heterogeneity of SCHLAP1 expression emphasizes the importance of analyzing multiple samples for determination of a patient's SCHLAP1 status.
Article
Biotechnology & Applied Microbiology
Jonas M. Stromme, Bjarne Johannessen, Susanne G. Kidd, Mari Bogaard, Kristina T. Carm, Xiaokang Zhang, Anita Sveen, Anthony Mathelier, Ragnhild A. Lothe, Ulrika Axcrona, Karol Axcrona, Rolf I. Skotheim
Summary: The study revealed extensive heterogeneity at the gene expression level in multifocal prostate cancer. Different malignant foci within the same patient showed similar levels of heterogeneity as tumors from different patients. Expression patterns linked to ETS status and extraprostatic extension were identified, and a set of 62 genes with low intrapatient heterogeneity and high interpatient heterogeneity were found, which could serve as prognostic biomarkers regardless of the sampled malignant focus.
CANCER GENE THERAPY
(2022)
Editorial Material
Urology & Nephrology
Rolf Skotheim, Ulrika Axcrona, Karol Axcrona
Summary: The research by Labanca et al strengthens the concept of an index tumor through the definition of aggressive molecular features. It suggests that molecular characterization will play a crucial role in radiogenomics development and guiding future treatment.
Article
Endocrinology & Metabolism
Anne M. A. Tryggestad, Karol Axcrona, Ulrika Axcrona, Iris Bigalke, Bjorn Brennhovd, Else M. Inderberg, Turid K. Honnashagen, Lisbeth J. Skoge, Guri Solum, Stein Saeboe-Larssen, Dag Josefsen, Richard W. Olaussen, Steinar Aamdal, Rolf I. Skotheim, Tor A. Myklebust, Dolores J. Schendel, Wolfgang Lilleby, Svein Dueland, Gunnar Kvalheim
Summary: This study aimed to reduce the risk of biochemical relapse in high-risk prostate cancer patients after robot-assisted laparoscopic prostatectomy by administering personalized dendritic cell vaccines as adjuvant therapy. The results showed promising efficacy of the vaccine in reducing biochemical relapse incidence, as well as associations between baseline immune response and vaccine response during the vaccination period. Further investigation in larger cohorts is warranted to validate these findings and explore the potential of dendritic cell vaccines in post-surgical treatment of high-risk prostate cancer.
Article
Medicine, Research & Experimental
Jacqueline Fontugne, Peter Y. Cai, Hussein Alnajar, Bhavneet Bhinder, Kyung Park, Huihui Ye, Shaham Beg, Verena Sailer, Javed Siddiqui, Mirjam Blattner-Johnson, Jaclyn A. Croyle, Zohal Noorzad, Carla Calagua, Theresa Y. MacDonald, Ulrika Axcrona, Mari Bogaard, Karol Axcrona, Douglas S. Scherr, Martin G. Sanda, Bjarne Johannessen, Arul M. Chinnaiyan, Olivier Elemento, Rolf Skotheim, Mark A. Rubin, Christopher E. Barbieri, Juan Miguel Mosquera
Summary: Prostate cancer is a multifocal disease with distinct molecular subtypes. This study reveals the presence of inter- and intrafocal molecular heterogeneity in primary prostate cancer, with approximately 60% of multifocal specimens showing discordant molecular alterations between foci. Collision tumors, characterized by discrepant molecular status within a single focus, are identified in about 10% of the specimens. These findings highlight the complexity of molecular heterogeneity in prostate cancer and have important implications for future genomic studies.
Article
Biochemistry & Molecular Biology
Camilla Wolowczyk, Ulrike Neckmann, Miriam Ragle Aure, Martina Hall, Bjarne Johannessen, Sen Zhao, Rolf Skotheim, Sonja B. Andersen, Rosalie Zwiggelaar, Tonje S. Steigedal, Ole Christian Lingjaerde, Kristine Kleivi Sahlberg, Eivind Almaas, Geir Bjorkoy
Summary: In breast cancer patients, the NRF2 gene is continuously activated in metastatic cells and tumors, with corresponding upregulation of related genes. Depletion of NRF2 increases reactive oxygen species levels and severely reduces tumor formation and lung metastasis. A set of NRF2-regulated genes is elevated in breast cancer biopsies and can significantly improve prognosis prediction.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Pathology
Christian H. Bergsland, Marine Jeanmougin, Seyed H. Moosavi, Aud Svindland, Jarle Bruun, Arild Nesbakken, Anita Sveen, Ragnhild A. Lothe
Summary: This study investigated the prognostic heterogeneity of different regulatory T cell (Treg) populations in colorectal cancer (CRC) using multiplex fluorescence immunohistochemistry and digital image analysis. The results showed that Treg infiltration in tumors was strongly correlated with the overall amount of T cells and was associated with a favorable prognosis among CRC patients who underwent complete tumor resection. However, high expression of the activation marker CD25 in Tregs was independently associated with an adverse outcome. Moreover, spatial analysis revealed a significant proximity between Tregs and CD8+ cells, which was associated with a poor survival rate. These findings highlight the importance of multi-marker and spatial analysis in accurately predicting patient outcomes in CRC.
Article
Oncology
Susanne G. Kidd, Mari Bogaard, Kristina T. Carm, Anne Cathrine Bakken, Aase M. V. Maltau, Marthe Lovf, Ragnhild A. Lothe, Karol Axcrona, Ulrika Axcrona, Rolf I. Skotheim
Summary: This study aimed to determine the prognostic value of candidate biomarkers transcriptional regulator ERG and related ETS family genes in prostate cancer, while considering tumor heterogeneity. The results showed that ERG protein has independent prognostic value in predicting biochemical and clinical recurrence of prostate cancer, and appears to have the greatest prognostic value for patients with Grade Groups 4-5.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Chiara Grasso, Maja Popovic, Elena Isaevska, Fulvio Lazzarato, Valentina Fiano, Daniela Zugna, John Pluta, Benita Weathers, Kurt D'Andrea, Kristian Almstrup, Lynn Anson-Cartwright, D. Timothy Bishop, Stephen J. Chanock, Chu Chen, Victoria K. Cortessis, Marlene D. Dalgaard, Siamak Daneshmand, Alberto Ferlin, Carlo Foresta, Megan N. Frone, Marija Gamulin, Jourik A. Gietema, Mark H. Greene, Tom Grotmol, Robert J. Hamilton, Trine B. Haugen, Russ Hauser, Robert Karlsson, Lambertus A. Kiemeney, Davor Lessel, Patrizia Lista, Ragnhild A. Lothe, Chey Loveday, Coby Meijer, Kevin T. Nead, Jeremie Nsengimana, Rolf I. Skotheim, Clare Turnbull, David J. Vaughn, Fredrik Wiklund, Tongzhang Zheng, Andrea Zitella, Stephen M. Schwartz, Katherine A. McGlynn, Peter A. Kanetsky, Katherine L. Nathanson, Lorenzo Richiardi
Summary: This study found that genetic variants within the MTHFR gene are associated with the risk of testicular germ cell tumors (TGCT), potentially affecting the establishment of DNA methylation patterns. This finding suggests that the pathogenesis of TGCT may be related to the status of the folate cycle, and this relation could be partly due to hereditary factors.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Kristina T. Carm, Bjarne Johannessen, Mari Bogaard, Anne Cathrine Bakken, Aase Maltau, Andreas M. Hoff, Ulrika Axcrona, Karol Axcrona, Ragnhild A. Lothe, Rolf Skotheim
Summary: Our study highlights the spatio-temporal heterogeneity of multifocal prostate cancer and emphasizes the importance of testing a recent sample in genomics-based precision medicine for metastatic prostate cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Meeting Abstract
Pathology
M. Bogaard, J. M. Stromme, S. G. Kidd, B. Johannessen, A. C. Bakken, R. A. Lothe, K. Axcrona, R. I. Skotheim, U. Axcrona