Review
Biochemistry & Molecular Biology
Karpinski Pawel, Sasiadek Maria Malgorzata
Summary: The CpG island methylator phenotype (CIMP) is an important manifestation of epigenetic instability in cancer. It has been extensively studied in various tumor types, but its use as a diagnostic marker and therapeutic target in solid tumors is limited by the lack of generalizability and reproducibility of epigenetic markers, as well as its poor predictive value in clinical outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Josephine Yates, Valentina Boeva
Summary: This study utilized a pan-cancer approach to define and explore CpG island methylator phenotype (CIMP) in 26 cancer types. The results confirmed the existence of CIMP in 19 cancers, showed its association with survival differences in eight cancer types, and identified potential drivers of CIMP. The study also found that CIMP was strongly correlated with tumor microenvironment characteristics.
BRIEFINGS IN BIOINFORMATICS
(2022)
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)
Review
Oncology
Xiaofei Zhang, Wenjun Zhang, Pingan Cao
Summary: As the population ages in China, the incidence of colorectal cancer is on the rise, with CpG island methylator phenotype (CIMP) playing an important role in its development. Recent studies have shown a close relationship between CIMP and specific clinicopathological phenotypes and multiple molecular phenotypes in colorectal cancer. This paper introduces the latest progress on CIMP colorectal cancer in terms of chemotherapeutic drugs, targeted agents, and small molecular methylation inhibitors, aiming to provide potential clinical treatment strategies for personalized and precise treatment of colorectal cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Article
Gastroenterology & Hepatology
Rossella Tricarico, Jozef Madzo, Gabrielle Scher, Maya Cohen, Jaroslav Jelinek, Shinji Maegawa, Rajeswari Nagarathinam, Carly Scher, Wen-Chi Chang, Emmanuelle Nicolas, Michael Slifker, Yan Zhou, Karthik Devarajan, Kathy Q. Cai, Tim Kwok, Pamela Nakajima, Jinfei Xu, Pietro Mancuso, Valentina Doneddu, Luigi Bagella, Riley Williams, Siddharth Balachandran, Nicholas Maskalenko, Kerry Campbell, Xueying Ma, Israel Canadas, Julen Viana-Errasti, Victor Moreno, Laura Valle, Sergei Grivennikov, Iuliia Peshkova, Natalia Kurilenko, Aleksandra Mazitova, Ekaterina Koltsova, Hayan Lee, Martin Walsh, Reuben Duttweiler, Johnathan R. Whetstine, Timothy J. Yen, Jean-Pierre Issa, Alfonso Bellacosa
Summary: Aberrant DNA methylation is common in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are not well understood. In this study, disruption of the Tet1 and/or Tdg genes in mice resulted in increased size and invasive features of colonic adenomas. Furthermore, Tet1 and Tdg mutations led to global DNA hypomethylation and CpG island hypermethylation in colonic adenomas. The mutations also upregulated inflammatory, immune, and interferon response genes.
Article
Oncology
Valentina Condelli, Giovanni Calice, Alessandra Cassano, Michele Basso, Maria Grazia Rodriquenz, Angela Zupa, Francesca Maddalena, Fabiana Crispo, Michele Pietrafesa, Michele Aieta, Alessandro Sgambato, Giampaolo Tortora, Pietro Zoppoli, Matteo Landriscina
Summary: This study identified and validated a novel epigenetic eight-gene signature, with hypermethylation of the promoter regions, that can predict poor outcomes for a subgroup of metastatic colorectal carcinomas. The study showed that methylation events were enriched in genes located on specific chromosomal regions associated with adenoma-to-carcinoma progression, providing prognostic information for identifying metastatic colorectal carcinomas with poor prognosis.
Article
Oncology
Oscar Murcia, Alejandro Martinez-Roca, Miriam Juarez, Mar Giner-Calabuig, Miren Alustiza, Cristina Mira, Carolina Mangas-Sanjuan, Eva Serrano, Francisco Antonio Ruiz-Gomez, Sandra Baile-Maxia, Lucia Medina, Cristina Alenda, Artemio Paya, Maria Rodriguez-Soler, Pedro Zapater, Rodrigo Jover
Summary: The study suggests that CIMP may be a useful marker for endoscopic surveillance after polypectomy, improving the accuracy in predicting the risk of metachronous advanced colorectal lesions (MACLs). Patients with CIMP+ polyps show a higher risk and shorter time to MACL development, even after adjustment for other factors. The addition of CIMP analysis enhances the sensitivity, negative predictive value, and overall accuracy in estimating MACL risk.
Article
Cell Biology
Junnan Liang, Tongtong Liu, Jingyu Liao, Lu Zhang, Mi Zhou, Weiqi Xu, Yi He, Guangzhen Cai, Guannan Jin, Jia Song, Ganxun Li, Huifang Liang, Zeyang Ding, Bixiang Zhang
Summary: The study identified a CIMP-related methylation signature specific for CCA (CMSC) that can classify patients into different risk groups and predict patient outcomes. Additionally, a subset of patients with an unfavorable prognosis correlated with CIMP-H was identified. Gene enrichment analysis suggested a potential mechanism of CIMP as a promoter of carcinogenesis by regulating proliferation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Oncology
Guang Yang, Xi (Richard) Yu, Daniel J. J. Weisenberger, Tao Lu, Gangning Liang
Summary: Human colorectal cancer (CRC) is a global health burden, especially for minority populations. The disease is complex, with diverse molecular features linked to the location of the primary tumor, posing challenges to treatment and patient outcome improvement. Liver and other organ system metastases are major causes of CRC-related mortality and obstacles to improving outcomes. This review summarizes CRC tumor subgroups, molecular features, treatments, outcomes, and disparities in health and metastases.
Article
Multidisciplinary Sciences
Daai Zhang, Chengcheng Zhong, Neil A. Smith, Robert de Feyter, Ian K. Greaves, Steve M. Swain, Ren Zhang, Ming-Bo Wang
Summary: This study shows that nucleotide mismatches can prevent intrinsic self-silencing of hpRNA transgenes in plants.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Dasa Jevsinek Skok, Nina Hauptman
Summary: This article investigates the CpG island methylator phenotype (CIMP) in colorectal cancer development, using unsupervised hierarchical clustering to identify four distinct subtypes. Through mapping methylated regions to Ensembl database, 253 genes were found to exhibit aberrant methylation in promoter regions, with bone morphogenic protein 4 (BMP4) being highlighted as the most prominent candidate. This finding highlights the potential role of BMP4 in colorectal cancer development and progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Dermatology
Kathleen Conway, Yihsuan S. Tsai, Sharon N. Edmiston, Joel S. Parker, Eloise A. Parrish, Honglin Hao, Pei Fen Kuan, Glynis A. Scott, Jill S. Frank, Paul Googe, David W. Ollila, Nancy E. Thomas
Summary: The study found that CIMP melanoma is associated with age, melanoma classification, and ulceration, and has a lower survival rate. CIMP melanoma exhibits hypermethylation of genes important in tumor progression and immunity, contradicting the fact that it occurs in early melanoma.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Oncology
Zeenat Jahan, Fahad A. Benthani, Nicola Currey, Hannah W. Parker, Jane E. Dahlstrom, C. Elizabeth Caldon, Maija R. J. Kohonen-Corish
Summary: DNA hypermethylation can cause gene silencing, which is an important mechanism in promoting cancer. This study found that MCC gene silencing is present in a subset of colorectal cancers that display high levels of methylation. The absence or reduction of MCC expression was also observed in tumors with hypomethylated regions of the gene. In cell culture experiments, the deletion of MCC increased the sensitivity of cancer cells to the chemotherapy drug irinotecan, and this effect was further enhanced by a targeted cancer drug, Olaparib. The findings suggest that MCC methylation may be a valuable biomarker for identifying colorectal cancers suitable for irinotecan therapy, potentially in combination with PARP inhibitors.
Article
Chemistry, Multidisciplinary
Fatih Demirel, Aras Turkoglu, Kamil Haliloglu, Baris Eren, Guller Ozkan, Pinar Uysal, Alireza Pour-Aboughadareh, Agnieszka Lesniewska-Bocianowska, Bita Jamshidi, Jan Bocianowski
Summary: This study investigated the effects of mammalian sex hormones on DNA damage and DNA methylation in wheat plants, and found that these hormones can alter the genomic stability and cytosine methylation status of wheat plants.
APPLIED SCIENCES-BASEL
(2023)
Article
Oncology
Artur Kowalik, Pawel Karpinski, Anna Markiewicz, Jolanta Orlowska-Heitzman, Bozena Romanowska-Dixon, Piotr Donizy, Mai P. Hoang
Summary: This study performed whole exome sequencing of 20 primary uveal melanoma cases and identified significant molecular alterations. BAP1 and GNA11 genes were found to have high mutation rates and correlated with metastasis. Other gene mutations were also detected. Further investigation is needed to determine the prognostic significance of GNAQ/GNA11 mutation and CDKN2A loss.
Article
Environmental Sciences
Barbara Zych, Anna Gorka, Aleksander Myszka, Dominika Bloniarz, Aleksandra Siekierzynska, Witold Blaz
Summary: Pregnancy and childbirth can lead to oxidative stress, which may negatively impact the fetus and labor. Monitoring oxidative stress parameters can help assess risk and newborn health in pregnancy. This study examined oxidative stress in mother-child pairs during physiological labor. Results showed lower total antioxidant status (TAS), glutathione peroxidase (GPx) activity, and zinc (Zn) concentration in maternal blood compared to umbilical cord blood, while superoxide dismutase (SOD) activity and copper (Cu) concentration were higher in maternal blood. Manganese (Mn) concentration was similar in both blood samples. The findings suggest depletion of redox reserves in women's blood during labor.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2023)
Article
Biochemistry & Molecular Biology
Pawel Kozlik-Siwiec, Sylwia Buregwa-Czuma, Izabela Zawlik, Sylwia Dziedzina, Aleksander Myszka, Joanna Zuk-Kuwik, Andzelika Siwiec-Kozlik, Jacek Zarychta, Krzysztof Okon, Lech Zareba, Jerzy Soja, Bogdan Jakiela, Michal Kepski, Jan G. Bazan, Stanislawa Bazan-Socha
Summary: This study compared the phenotypic features, bronchial epithelial gene expression, and functional and structural measures of airway remodeling between moderate to severe eosinophilic asthma (EA) and non-eosinophilic asthma (NEA) patients. The results showed that there was no significant difference in airway remodeling between EA and NEA patients, but EA patients had increased expression of genes involved in immune response and inflammation, and decreased expression of genes involved in epithelial integrity and histone acetylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Nafeesa Moksud, Marta Wagner, Konrad Pawelczyk, Irena Porebska, Beata Muszczynska-Bernhard, Aneta Kowal, Andrzej Wisniewski, Monika Kosacka, Julia Konczak, Pawel Karpinski, Dominik Frydryk, Anna Andrzejczak, Lidia Karabon, Piotr Kusnierczyk, Monika Jasek
Summary: This study found that single nucleotide polymorphisms (SNPs) of PDCD1, CD274, and HAVCR2 genes are associated with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes, including squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). Specific genotypes of rs4143815 and rs4742098 were associated with increased risk of developing LUSC. Additionally, rs4143815 was found to be an independent predictor of the age at diagnosis of LUAD, and rs10057302 was associated with overall survival in LUSC. Furthermore, NSCLC carriers of rs11568821 had a higher risk of death compared to carriers of CC genotype.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Psychiatry
Tomasz Grazlewski, Jolanta Kucharska-Mazur, Blazej Misiak, Jerzy Samochowiec
Summary: According to the diathesis-stress model, disturbances of the HPA axis are believed to be involved in the development and progression of psychosis. This study aims to present the evidence on cortisol awakening response (CAR) abnormalities in psychotic disorders and at-risk states. The research suggests that the CAR is blunted in patients with first-episode psychosis or schizophrenia, but the results are inconclusive for individuals with at-risk states. More research is needed to further understand these findings.
ARCHIVES OF PSYCHIATRY AND PSYCHOTHERAPY
(2023)
Article
Psychiatry
Blazej Misiak, Patryk Piotrowski, Jerzy Samochowiec
Summary: This study compared the effects of interconnections between different domains of psychopathology and neurocognition on social functioning in patients during acute phase of psychosis and those in remission of positive and disorganization symptoms. Attention and immediate memory were found to play a central role in shaping functional impairments in both patient groups.
Article
Psychiatry
Jerzy Samochowiec, Dorota Frydecka, Karolina Skonieczna-Zydecka, Meryam Schouler-Ocak, Bernardo Carpinello, Eka Chkonia, Geert Dom, Peter Falkai, Blazej Misiak, Mariana Pinto da Costa, Jan Wise, Livia de Picker, Simavi Vahip, Danuta Wasserman, Silvana Galderisi, Przemyslaw Bienkowski
Summary: This study investigates the current status of ethical codes and practices in countries belonging to the European Psychiatric Association (EPA). Most countries rely on mission statements and internal documents to address ethical issues in psychiatry, including medical malpractice, workplace bullying, plagiarism, academic fraud, sexual abuse, and discrimination/racism. NPAs play an active role in defining ethical standards for mental health care professionals, and future collaboration under the EPA's umbrella could establish a database of local ethical documents translated into English for all EPA members.
EUROPEAN PSYCHIATRY
(2023)
Article
Dermatology
Mai P. Hoang, Pawel Karpinski, Miguel Zuniga-Castillo, Ruth K. Foreman, Kevin S. Emerick, Arthur J. Sober
Summary: Histologic margin status is the strongest predictor of progression for lentigo maligna melanoma. Patients with positive or close/<3 mm histologic margins should consider a re-excision due to the increased risk of relapse.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Pawel Karpinski, Ivy Rosales, Lukasz Laczmanski, Artur Kowalik, Scott Wenson, Mai P. Hoang
Summary: Two possible pathways for Merkel cell carcinoma (MCC) pathogenesis are the integration of Merkel cell polyomavirus (MCPyV) and UV irradiation. This study found that MCPyV-negative MCCs showed higher expression of genes associated with epithelial-mesenchymal transition (EMT) compared to MCPyV-positive MCCs. It was also observed that MCPyV-negative MCCs had significant enrichment of EMT-related genes and pathways, as well as higher expression of EMT-associated proteins. These findings highlight the importance of EMT pathways in MCPyV-negative MCCs and their potential therapeutic relevance.
LABORATORY INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Pawel Karpinski, Paulina Zebrowska-Rozanska, Dorota Kujawa, Lukasz Laczmanski, Jerzy Samochowiec, Marcin Jablonski, Piotr Plichta, Patryk Piotrowski, Tomasz Bielawski, Blazej Misiak
Summary: This study aimed to compare gut microbiota between patients with schizophrenia and controls, taking into consideration factors such as exposure stress, dietary habits, metabolic parameters, and clinical manifestation. The results showed increased abundance of Lactobacillus and Limosilactobacillus and decreased abundance of Faecalibacterium and Paraprevotella in patients with schizophrenia. Machine learning analysis revealed that these gut microbiota differences were associated with factors such as psychosocial stress, poor nutrition, lipid profile alterations, and cognitive impairment.
PSYCHONEUROENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Michal Bloch, Piotr Gasperowicz, Sylwester Gerus, Katarzyna Rasiewicz, Arleta Lebioda, Pawel Skiba, Rafal Ploski, Dariusz Patkowski, Pawel Karpinski, Robert Smigiel
Summary: Esophageal atresia (EA) is a common malformation of the upper gastrointestinal tract, with an estimated incidence of 1 in 3500 births. The exact cause of isolated EA is unknown, but it is believed to have a multifactorial etiology, including epigenetic gene expression modifications. A study on twins revealed differences in methylation profiles between EA patients and their healthy siblings, with hypermethylation observed in the promoters of 219 genes and hypomethylation in the promoters of 78 genes. Pathway enrichment analysis highlighted the significant differences in methylation profile of 10 hypermethylated genes in the Rho GTPase pathway.
Review
Medicine, General & Internal
Malgorzata Madej, Pawel Karpinski, Hayane Akopyan, Michal Witt, Maria M. Sasiadek
Summary: The progress in molecular biology has changed our understanding of human diseases. Whole genome analyses have allowed for the identification of unknown diseases. Molecular diagnosis is replacing clinical diagnosis in difficult cases. Construction and sharing of large databases are crucial for genetic research and clinical characteristics of rare diseases. Legal and ethical issues surrounding genetic testing and personal data protection must be addressed. This paper explores the benefits and risks of international sharing of genetic databases and discusses legal provisions in the EU, US, and China.
POLISH ARCHIVES OF INTERNAL MEDICINE-POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ
(2023)
Article
Psychiatry
Maksymilian Rejek, Blazej Misiak
Summary: This study investigates the association of the exposome score (ES) with psychosis risk in a non-clinical population. The results show that the ES is associated with the extended psychosis phenotype, suggesting its potential to identify individuals who may benefit from further psychosis risk assessment.
JOURNAL OF PSYCHIATRIC RESEARCH
(2024)
Meeting Abstract
Psychiatry
D. Cavaleri, C. A. Capogrosso, P. Guzzi, B. Misiak, G. Bernasconi, M. Re, C. Crocamo, F. Bartoli, G. Carra
EUROPEAN PSYCHIATRY
(2023)
Review
Endocrinology & Metabolism
Daniele Cavaleri, Chiara Alessandra Capogrosso, Pierluca Guzzi, Gianna Bernasconi, Martina Re, Blazej Misiak, Cristina Crocamo, Francesco Bartoli, Giuseppe Carra
Summary: This study investigated the differences in blood concentrations of anterior pituitary hormones between drug-naive individuals with first-episode psychosis and healthy controls. The results showed that drug-naive individuals with first-episode psychosis had higher levels of ACTH and PRL, and lower levels of TSH compared to healthy controls.
PSYCHONEUROENDOCRINOLOGY
(2023)