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Molecular subtype

Hironori Aoki, Eiichiro Yamamoto, Hiro-O Yamano, Tamotsu Sugai, Tomoaki Kimura, Yoshihito Tanaka, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Taku Harada, Gota Sudo, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Takeshi Niinuma, Masahiro Kai, Masanori Nojima, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L)...
March 15, 2018: Digestive Diseases and Sciences
Claudia Caroline Veloso da Silva-Camargo, Rosimeri Kuhl Svoboda Baldin, Nayanne Louise Costacurta Polli, Amanda Pereira Agostinho, Marcia Olandosk, Lúcia de Noronha, Vanessa Santos Sotomaior
Objective: Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer...
February 2018: Cancer Biology & Medicine
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Timothy Kwang Yong Tay, Aye Aye Thike, Nirmala Pathmanathan, Ana Richelia Jara-Lazaro, Jabed Iqbal, Adeline Shi Hui Sng, Heng Seow Ye, Jeffrey Chun Tatt Lim, Valerie Cui Yun Koh, Jane Sie Yong Tan, Joe Poh Sheng Yeong, Zi Long Chow, Hui Hua Li, Chee Leong Cheng, Puay Hoon Tan
Background: Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers...
February 20, 2018: Oncotarget
Zhong Ni, Xiting Wang, Tianchen Zhang, Linlin Li, Jianxue Li
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database...
April 2018: Experimental and Therapeutic Medicine
Rokaya El Ansari, Madeleine L Craze, Maria Diez-Rodriguez, Christopher C Nolan, Ian O Ellis, Emad A Rakha, Andrew R Green
Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity and patient outcome. This study aimed to evaluate the biological and prognostic value of the membrane solute carrier, SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. SLC3A2 was assessed at the genomic level, using METABRIC data (n = 1980), and at the proteomic level, using immunohistochemistry on tissue microarray (TMA) sections constructed from a large well-characterised primary BC cohort (n = 2500)...
March 16, 2018: British Journal of Cancer
Vonn Walter, Xiaoying Yin, Matthew D Wilkerson, Christopher R Cabanski, Ni Zhao, Ying Du, Mei Kim Ang, Michele C Hayward, Ashley H Salazar, Katherine A Hoadley, Karen Fritchie, Charles J Sailey, Mark C Weissler, William W Shockley, Adam M Zanation, Trevor Hackman, Leigh B Thorne, William D Funkhouser, Kenneth L Muldrew, Andrew F Olshan, Scott H Randell, Fred A Wright, Carol G Shores, D Neil Hayes
[This corrects the article DOI: 10.1371/journal.pone.0056823.].
2018: PloS One
Jennifer Karmouch, Alexandros Protonotarios, Petros Syrris
PURPOSE OF REVIEW: To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM...
March 14, 2018: Current Opinion in Cardiology
Noor Afshan, Mukarram Bashir, Hamid Nawaz Tipu, Mohammad Hussain
The association of spondyloarthropathies with different alleles of human leukocyte antigen (HLA) B*27 is well established. Different subtypes of HLA-B*27 may be linked with different ethnic groups, distinct clinical manifestations, specific age of onset and different prognoses. Polymerase chain reaction with sequence specific primers (PCR-SSP) is the most frequently adapted molecular method used for the recognition of HLA-B*27-specific DNA sequences. The aim of the present study was to standarise an in-house protocol of PCR-SSP for HLA-B*27 allele detection for use in the Armed Forces Institute of Pathology (AFIP), Pakistan, with consideration of its cost effectiveness...
April 2018: Biomedical Reports
Feng Shen, Qing Guo, Qi Hu, Ailiang Zeng, Weining Wu, Wei Yan, Yongping You
Nuclear factor κB (NF-κB) exhibits an important role in inflammation and tumorigenesis. The key regulatory protein of the pathway, RELB Proto-Oncogene, NF-KB Subunit (relB), is overexpressed and associated with the pathogenesis of a variety of malignant tumors. However, the molecular features and clinical signature of relB expression in gliomas remains to be elucidated. The present study obtained the raw sequencing data of 325 glioma samples of all grades from the Chinese Glioma Genome Atlas (CGGA) database and human glioma cell line (LN229) from the Chinese Academy of Sciences cell bank...
April 2018: Oncology Letters
S Y N Jamaludin, I Azimi, F M Davis, A A Peters, T J Gonda, E W Thompson, S J Roberts-Thomson, G R Monteith
CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells...
April 2018: Oncology Letters
Yi-Shu Huang, Nien-Yi Chiang, Gin-Wen Chang, Hsi-Hsien Lin
The evolutionarily conserved adhesion G protein-coupled receptors (aGPCRs) play critical roles in biological processes as diverse as brain development, cell polarity and innate immune functions. A defining feature of aGPCRs is the GPCR autoproteolysis inducing (GAIN) domain capable of self-catalytic cleavage, resulting in the generation of an extracellular N-terminal fragment (NTF) and a seven-transmembrane C-terminal fragment (CTF) involved in the cellular adhesion and signaling functions, respectively. Interestingly, two different NTF subtypes have previously been identified, namely an NTF that couples non-covalently with the CTF and a membrane-associated NTF that tethers on cell surface independently...
March 14, 2018: Scientific Reports
Tanziyah Muqeem, Biswarup Ghosh, Vitor Pinto, Angelo C Lepore, Manuel Covarrubias
Presynaptic voltage-gated K+ (Kv) channels in dorsal root ganglion (DRG) neurons are thought to regulate nociceptive synaptic transmission in the spinal dorsal horn. However, the Kv channel subtypes responsible for this critical role have not been identified. The Kv3.4 channel is particularly important because it is robustly expressed in DRG nociceptors, where it regulates action potential (AP) duration. Furthermore, Kv3.4 dysfunction is implicated in the pathophysiology of neuropathic pain in multiple pain models...
March 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
A Arfaoui Toumi, A Blel, R Aloui, H Zaibi, M Ksentinini, M S Boudaya, N Znaidi, Y Zidi, H Aouina, S Rammeh Rommani
BACKGROUND: Despite recent advances, non-small cell lung cancer carries a grim prognosis. For appropriate treatment selection, the updated guidelines recommend broad molecular profiling for all patients with pulmonary adenocarcinoma. Precise histological subtyping and targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) testing are mandatory. METHODS: Herein, we assessed the EGFR mutation status of 26 formalin fixed-paraffin embedded (FFPE) samples of lung adenocarcinoma...
March 11, 2018: Current Research in Translational Medicine
Suijuan Zhong, Shu Zhang, Xiaoying Fan, Qian Wu, Liying Yan, Ji Dong, Haofeng Zhang, Long Li, Le Sun, Na Pan, Xiaohui Xu, Fuchou Tang, Jun Zhang, Jie Qiao, Xiaoqun Wang
The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex...
March 14, 2018: Nature
F Pietrantonio, F Di Nicolantonio, A B Schrock, J Lee, F Morano, G Fucà, P Nikolinakos, A Drilon, J F Hechtman, J Christiansen, K Gowen, G M Frampton, P Gasparini, D Rossini, C Gigliotti, S T Kim, M Prisciandaro, J Hodgson, A Zaniboni, V K Chiu, M Milione, R Patel, V Miller, A Bardelli, L Novara, L Wang, S Pupa, G Sozzi, J Ross, M Di Bartolomeo, A Bertotti, S Ali, L Trusolino, A Falcone, F de Braud, C Cremolini
Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors...
March 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Kentaro Inamura
Immunohistochemistry is a widely available technique that is less challenging and can provide clinically meaningful results quickly and cost-efficiently in comparison with other techniques. In addition, immunohistochemistry allows for the evaluation of cellular localization of proteins in the context of tumor structure. In an era of precision medicine, pathologists are required to classify lung cancer into specific subtypes and assess biomarkers relevant to molecular-targeted therapies. This review summarizes the hot topics of immunohistochemistry in lung cancer, including (i) adenocarcinoma vs squamous cell carcinoma; (ii) neuroendocrine markers; (iii) ALK, ROS1, and EGFR; (iv) PD-L1 (CD274); (v) lung carcinoma vs malignant mesothelioma; and (vi) NUT carcinoma...
March 14, 2018: Cancers
Lara Kujtan, Arif Hussain, Janakiraman Subramanian, Ashiq Masood
PURPOSE OF REVIEW: Recent advances in next-generation sequencing have allowed for detailed molecular analysis of urothelial carcinomas, with potentially significant clinical implications for personalized treatment. Our objective in this review is to highlight studies from the past year that have furthered the understanding of urothelial cancer genomics. RECENT FINDINGS: Recent studies by The Cancer Genome Atlas consortium further characterized urothelial carcinomas via molecular subtyping, and a schema was proposed to match each subtype with potential therapeutic implications...
March 13, 2018: Current Opinion in Oncology
Timothy E Sweeney, Tej D Azad, Michele Donato, Winston A Haynes, Thanneer M Perumal, Ricardo Henao, Jesús F Bermejo-Martin, Raquel Almansa, Eduardo Tamayo, Judith A Howrylak, Augustine Choi, Grant P Parnell, Benjamin Tang, Marshall Nichols, Christopher W Woods, Geoffrey S Ginsburg, Stephen F Kingsmore, Larsson Omberg, Lara M Mangravite, Hector R Wong, Ephraim L Tsalik, Raymond J Langley, Purvesh Khatri
OBJECTIVES: To find and validate generalizable sepsis subtypes using data-driven clustering. DESIGN: We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700). SETTING: Retrospective analysis. SUBJECTS: Persons admitted to the hospital with bacterial sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A unified clustering analysis across 14 discovery datasets revealed three subtypes, which, based on functional analysis, we termed "Inflammopathic, Adaptive, and Coagulopathic...
March 13, 2018: Critical Care Medicine
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as one disease, accumulated evidences point to the clinical heterogeneity of this disease which translates into disparity in outcomes between patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last ten years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
March 14, 2018: Annals of Medicine
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