Review
Oncology
Mojun Zhu, Zhaohui Jin, Joleen M. Hubbard
Summary: Microsatellite instability (MSI) is a genetic predisposition to DNA damage, detectable through sequencing or immunohistochemistry, and associated with a high neoantigen load and favorable response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI serves as a predictive biomarker for ICIs with varying clinical utility depending on tumor type, potentially explained by the complex tumor microenvironment. This review explores the predictive and prognostic value of MSI in non-colorectal cancers of the digestive system and strategies to overcome immunotherapy resistance.
Article
Cell Biology
Aya Shinozaki-Ushiku, Akiko Kunita, Akiko Iwasaki, Moe Kato, Sho Yamazawa, Hiroyuki Abe, Tetsuo Ushiku
Summary: This study aimed to clarify the detailed MSI profiles of non-colorectal gastrointestinal cancers and investigate the differences from colorectal cancers. The results showed that MSI testing is applicable to non-colorectal gastrointestinal cancers, but a subset of cases may yield false-negative results, emphasizing the need for careful interpretation and analysis of results.
Article
Oncology
Cheng Liu, Xuan Zou, Guoxin Song, Xingchen Fan, Shuang Peng, Shiyu Zhang, Xiangnan Geng, Xin Zhou, Tongshan Wang, Wenfang Cheng, Wei Zhu
Summary: This study established a predictive model of miRNAs and mRNAs to distinguish MSI versus MSS CRCs and elucidated their potential molecular mechanisms and biological functions.
Article
Oncology
Satu Maki-Nevala, Sanjeevi Ukwattage, Alisa Olkinuora, Henrikki Almusa, Maarit Ahtiainen, Ari Ristimaki, Toni Seppala, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Summary: Ulcerative colitis increases the risk of colorectal cancer, and this study examined the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). Subgroups within CA-CRC were identified with different mutational loads and signatures, which may guide clinical management and therapy options. Lynch syndrome tumors showed a higher degree of hypermutability compared to CA-CRC subgroups.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Gastroenterology & Hepatology
Claire Boyer, David Sefrioui, Romain Cohen, Romain Chautard, Marine Perrier, Hugo Lebrun, Gael Goujon, Vincent Hautefeuille, Marie Dior, Thomas Walter, Florence Mary, Silvain Manfredi, Francois-Xavier Caroli-Bosc, Baptiste Cervantes, Romain Coriat, Elise Deluche, Aziz Zaanan, Raphael Olivier, Olivier Bouche, Guillaume Piessen, Thierry Lecomte, Christophe Louvet, Pierre Michel, Thomas Aparicio, Thierry Andre, Julien Taieb, Violaine Randrian, David Tougeron
Summary: This French multicenter study evaluated the overall survival of patients with dMMR/MSI digestive non-colorectal tumors. The results showed that most tumors were oesophago-gastric or small bowel adenocarcinomas and were at a localized stage at diagnosis. Patients with localized tumors and R0 resection had a median overall survival of 134.0 +/- 64.2 months. Overall, dMMR/MSI digestive non-colorectal tumors have a good prognosis, but advanced tumors treated with standard chemotherapy have a poor prognosis.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Vitaly Shubin, Yury Shelygin, Sergey Achkasov, Oleg Sushkov, Ilya Nazarov, Alexey Ponomarenko, Iuliia Alimova, Anna Loginova, Aleksey Tsukanov
Summary: The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. The results showed that patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. Patients whose tumors had MSI status had higher overall and disease-free survival rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rimma S. Mulkidjan, Evgeniya S. Saitova, Elena V. Preobrazhenskaya, Karimat A. Asadulaeva, Mikhail G. Bubnov, Ekaterina A. Otradnova, Darya M. Terina, Sofia S. Shulga, Darya E. Martynenko, Maria V. Semina, Evgeniya V. Belogubova, Vladislav I. Tiurin, Priscilla S. Amankwah, Aleksandr S. Martianov, Evgeny N. Imyanitov
Summary: This study conducted a comprehensive analysis of gene rearrangements in tumors with microsatellite instability (MSI). Gene fusions were detected in colorectal carcinomas (CRCs), gastric cancers (GCs), and endometrial cancers (ECs), but not in cervical carcinomas (CCs), pancreatic cancers (PanCs), cholangiocarcinomas (ChCs), and ovarian cancers (OCs). The frequency of gene rearrangements was highest in KRAS/NRAS/BRAF wild-type CRCs. There was a higher frequency of translocations in CRC patients aged above 50 years, particularly in tumors with normal KRAS/NRAS/BRAF status.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Takahiro Utsumi, Shin'ichi Miyamoto, Takahiro Shimizu, Kasumi Yokogawa, Yuki Nakanishi, Mitsuhiro Nikaido, Ayako Hirata, Miyu Nishida, Ikuo Aoyama, Tomoko Okuno, Akihiko Yoshizawa, Akihiro Kaneda, Yoshiharu Sakai, Chiharu Kawanami, Hiroshi Seno
Summary: Spontaneous regression in colorectal cancer is rare and often associated with specific endoscopic characteristics, lack of DNA mismatch repair proteins, and a deficiency in mismatch repair (dMMR). The activation of anti-tumor host immune responses through increased tumor-infiltrating lymphocytes may play a role in the spontaneous regression of colorectal cancer.
DIGESTIVE ENDOSCOPY
(2021)
Article
Oncology
Roel M. M. Bogie, Chantal M. C. le Clercq, Quirinus J. M. Voorham, Martijn Cordes, Daoud Sie, Christian Rausch, Evert van den Broek, Sara D. J. de Vries, Nicole C. T. van Grieken, Robert G. Riedl, Prapto Sastrowijoto, Ernst-Jan Speel, Rein Vos, Bjorn Winkens, Manon van Engeland, Bauke Ylstra, Gerrit A. Meijer, Ad A. M. Masclee, Beatriz Carvalho
Summary: PCCRCs are more commonly located proximally, non-polypoid appearing, early stage, and poorly differentiated compared to DCRCs. They also show significantly less 18q loss and are more commonly CIMP high and MSI. Molecular features associated with sessile serrated lesions and non-polypoid colorectal neoplasms may contribute to the development of PCCRCs.
BRITISH JOURNAL OF CANCER
(2022)
Editorial Material
Cell Biology
Gayathri Anandappa, Michael J. Overman
Summary: In a recent study, Amodio and colleagues discovered a method to modulate immunosurveillance in colorectal tumors by manipulating DNA mismatch repair heterogeneity. They found that enriching the MMR deficient component using 6-thioguanine can improve tumor control in murine models.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Ilya G. Serebriiskii, Valery Pavlov, Rossella Tricarico, Grigorii Andrianov, Emmanuelle Nicolas, Mitchell Parker, Justin Newberg, Garrett Frampton, Joshua E. Meyer, Erica A. Golemis
Summary: Loss or dysfunction of the PTEN tumor suppressor gene can activate pro-tumorigenic signaling pathways. In this study, the authors analyze sequencing data from a large cohort of colorectal cancer patients with PTEN mutations and identify distinct patterns of associations with genomic and clinical features.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Violaine Randrian, Camille Evrard, David Tougeron
Summary: A defective mismatch repair system leads to microsatellite instability, resulting in high mutation burden in tumors, with some mutations producing neo-antigens that trigger anti-tumoral immune response. Non-metastatic MSI tumors have high immune infiltrates and good prognosis, while metastatic MSI tumors, having evaded immune response, are associated with poor prognosis and chemoresistance. Immune checkpoint inhibitors (ICI) are effective in dMMR/MSI mCRC, but some patients may develop primary or secondary resistance, prompting the development of strategies targeting other immune checkpoints or utilizing vaccination and modification of microbiota to overcome resistance.
Article
Oncology
Hui Wang, Zhi-Wei Li, Qiuxiang Ou, Xue Wu, Misako Nagasaka, Yang Shao, Sai-Hong Ignatius Ou, Yu Yang
Summary: We report a prevalence of approximately 0.7% for NTRK-positive colorectal cancer (CRC) by genetically profiling 2519 colonic and rectal tumors. NTRK gene fusions frequently co-occur with APC and TP53 aberrations, while they are almost always mutually exclusive with RAS/BRAF oncogenic alterations. NTRK-driven CRC patients show increased TMB, high microsatellite instability, and an enrichment for POLE/POLD1 mutations when compared to the molecularly unstratified CRC population.
Article
Medicine, General & Internal
Bill H. Diplas, Ryan Ptashkin, Joanne F. Chou, Shalom Sabwa, Michael B. Foote, Benoit Rousseau, Guillem Argiles, James Robert White, Caitlin M. Stewart, Kelly Bolton, Sree B. Chalasani, Avni M. Desai, Zoe Goldberg, Ping Gu, Jia Li, Marina Shcherba, Alice Zervoudakis, Andrea Cercek, Rona Yaeger, Neil H. Segal, David H. Ilson, Geoffrey Y. Ku, Ahmet Zehir, Marinela Capanu, Yelena Y. Janjigian, Luis A. Diaz, Steven B. Maron
Summary: This retrospective cohort study analyzed 633 patients with metastatic gastrointestinal tract cancer and found that clonal hematopoiesis (CH) was associated with survival outcomes. However, the association with cancer therapy efficacy and toxicity has not been established.
Article
Oncology
Kuo-Hsing Chen, Liang-In Lin, Chang-Tsu Yuan, Li-Hui Tseng, Yu-Liang Chao, Yi-Hsin Liang, Jin-Tung Liang, Been-Ren Lin, Ann-Lii Cheng, Kun-Huei Yeh
Summary: In Taiwan, distinct clinicopathological features were identified for CIMP-high CRC among different age groups. Our data suggest the association between BMI >= 27.5 kg/m(2) and CIMP-high CRC in patients younger than 50 years.
BRITISH JOURNAL OF CANCER
(2021)
Editorial Material
Gastroenterology & Hepatology
Christian Schulz, Behnam Kalali, Alexander Link, Markus Gerhard, Peter Malfertheiner
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Stephan Buch, Hamish Innes, Philipp Ludwig Lutz, Hans Dieter Nischalke, Jens U. Marquardt, Janett Fischer, Karl Heinz Weiss, Jonas Rosendahl, Astrid Marot, Marcin Krawczyk, Markus Casper, Frank Lammert, Florian Eyer, Arndt Vogel, Silke Marhenke, Johann von Felden, Rohini Sharma, Stephen Rahul Atkinson, Andrew McQuillin, Jacob Nattermann, Clemens Schafmayer, Andre Franke, Christian Strassburg, Marcella Rietschel, Heidi Altmann, Stefan Sulk, Veera Raghavan Thangapandi, Mario Brosch, Carolin Lackner, Rudolf E. Stauber, Ali Canbay, Alexander Link, Thomas Reiberger, Mattias Mandorfer, Georg Semmler, Bernhard Scheiner, Christian Datz, Stefano Romeo, Stefano Ginanni Corradini, William Lucien Irving, Joanne R. Morling, Indra Neil Guha, Eleanor Barnes, M. Azim Ansari, Jocelyn Quistrebert, Luca Valenti, Sacha A. Mueller, Marsha Yvonne Morgan, Jean-Francois Dufour, Jonel Trebicka, Thomas Berg, Pierre Deltenre, Sebastian Mueller, Jochen Hampe, Felix Stickel
Summary: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
Article
Genetics & Heredity
Yasmin Soares de Lima, Coral Arnau-Collell, Jenifer Munoz, Cristina Herrera-Pariente, Leticia Moreira, Teresa Ocana, Marcos Diaz-Gay, Sebastia Franch-Exposito, Miriam Cuatrecasas, Sabela Carballal, Anael Lopez-Novo, Lorena Moreno, Guerau Fernandez, Aranzazu Diaz de Bustamante, Sophia Peters, Anna K. Sommer, Isabel Spier, Iris B. A. W. te Paske, Yasmijn J. van Herwaarden, Antoni Castells, Luis Bujanda, Gabriel Capella, Verena Steinke-Lange, Khalid Mahmood, JiHoon Eric Joo, Julie Arnold, Susan Parry, Finlay A. Macrae, Ingrid M. Winship, Christophe Rosty, Joaquin Cubiella, Daniel Rodriguez-Alcalde, Elke Holinski-Feder, Richarda de Voer, Daniel D. Buchanan, Stefan Aretz, Clara Ruiz-Ponte, Laura Valle, Francesc Balaguer, Laia Bonjoch, Sergi Castellvi-Bel
Summary: Rare germline variants in the WNK2 gene were identified through functional evaluation of a candidate gene and replication in additional SPS cohorts. These variants may affect protein function in the MAPK pathway, thereby increasing the risk for SPS.
JOURNAL OF MEDICAL GENETICS
(2023)
Letter
Biochemistry & Molecular Biology
Keisuke Okuno, Raju Kandimalla, Marta Mendiola, Francesc Balaguer, Luis Bujanda, Carlos Fernandez-Martos, Jorge Aparicio, Jaime Feliu, Masanori Tokunaga, Yusuke Kinugasa, Joan Maurel, Ajay Goel
Article
Genetics & Heredity
Divya Sahu, Chen-Ching Lin, Ajay Goel
Summary: This study identified eRNA panels that can predict tumor recurrence in patients with colorectal cancer. These panels outperformed TNM staging in predicting recurrence and showed excellent accuracy. The findings of this study have the potential to improve risk stratification and guide precision oncology treatments for colorectal cancer patients.
Article
Gastroenterology & Hepatology
Francisco J. Caballero-Camino, Pedro M. Rodrigues, Fredrik Wangsell, Alona Agirre-Lizaso, Paula Olaizola, Laura Izquierdo-Sanchez, Maria J. Perugorria, Luis Bujanda, Bo Angelin, Sara Straniero, Anna Walleback, Ingemar Starke, Per-Goran Gillberg, Ellen Strangberg, Britta Bonn, Jan P. Mattsson, Martin R. Madsen, Henrik H. Hansen, Erik Lindstrom, Peter Akerblad, Jesus M. Banales
Summary: The ASBT inhibitor A3907 improves cholestatic liver diseases by clearing circulating bile acids and protecting liver function. A3907 targets ASBT in the intestine, liver, and kidney, leading to improved bilirubin and liver injury markers. A3907 is well tolerated in healthy individuals, supporting further clinical development.
Review
Biochemistry & Molecular Biology
Nayra Felipez, Sheyla Montori, Naroa Mendizuri, Joan Llach, Pedro G. G. Delgado, Leticia Moreira, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Eduardo Albeniz
Summary: Gastric cancer is a global public health problem with high mortality rates. Biomarker research is crucial for early detection of gastric cancer. Technological advances have identified several potential biomarkers, but their low specificity in biofluids limits their clinical use. Recent research focuses on exploring gastric juice as an alternative source for biomarker identification, as it contains disease-specific biomarkers generated at the site of damage. This narrative review describes potential biomarkers for gastric cancer screening in gastric juice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Katrin Bose, Florian G. Scurt, Cosima Thon, Sabine Franke, Christian Schulz, Peter Malfertheiner, Alexander Link
Summary: This study aimed to evaluate DNA methylation as a diagnostic tool for differentiating between benign and malignant ascites. The results showed that methylation levels were associated with ascites in patients with tumors, but not in patients without tumors. In addition, inflammatory cells were also found to be related to DNA methylation changes.
JOURNAL OF GASTROINTESTINAL AND LIVER DISEASES
(2023)
Review
Gastroenterology & Hepatology
Dan Dumitrascu, Igor Bakulin, Annalisa Berzigotti, Marilia Cravo, Laura Gombosova, Milan Lukas, Anna Pietrzak, Jose Maria Remes-Troche, Manuel Romero-Gomez, Mercedes Amieva Balmori, Tiago Curdia Goncalves, Lamine Hamzaoui, Radovan Juricek, Leticia Moreira, Katarzyna Neubauer, Teodora Surdea-Blaga, Igor N. Tikhonov, Jan Trna, Gianluca Ianiro, Francesca Romana Ponziani, Antonio Gasbarrini
Summary: Various environmental factors can lead to gut microbial imbalance and the development of diseases. Hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are all related to dysfunction of the gut-liver-brain axis, but the pathophysiology differs for each condition.
JOURNAL OF GASTROINTESTINAL AND LIVER DISEASES
(2023)
Article
Gastroenterology & Hepatology
Joel Flores-Arriaga, Maria C. Aso, Arantzazu Izagirre, Ami D. Sperber, Olafur S. Palsson, Shrikant I. Bangdiwala, Angel Lanas, Luis Bujanda, Beatriz Lobo, Carmen Alonso-Cotoner, Alex Sanchez-Pla, Javier Santos
Summary: The study used data from the Rome Foundation Global Epidemiology Study to assess the prevalence and burden of gut-brain disorders in Spain. The survey, completed by 2072 participants, revealed that 43.6% of respondents met diagnostic criteria for at least one disorder, with functional constipation being the most prevalent. The study highlights the need for specialized training and future research in this area.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Article
Cell Biology
Katsuki Miyazaki, Yuji Morine, Caiming Xu, Chiharu Nakasu, Yuma Wada, Hiroki Teraoku, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Mitsuo Shimada, Ajay Goel
Summary: This study demonstrates that the combination of Curcumin and Lenvatinib exhibits synergistic anti-tumor efficacy in Lenvatinib-resistant HCC cell lines. Curcumin reverses Lenvatinib resistance through inhibition of the EGFR pathway. These findings suggest that the combination therapy has potential clinical application for adjunctive treatment in HCC.
Article
Chemistry, Medicinal
Katsuki Miyazaki, Caiming Xu, Mitsuo Shimada, Ajay Goel
Summary: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. Limitations of current CRC chemotherapeutic drugs include toxicity, side effects, and high costs. In this study, a combination of curcumin and andrographis showed superior anti-tumor effects in CRC cells by inhibiting cell proliferation, invasion, colony formation, and inducing apoptosis. The combination treatment also activated the ferroptosis pathway and downregulated the expression of GPX-4 and FSP-1, leading to accumulation of reactive oxygen species and lipid peroxides in CRC cells.
Article
Medicine, General & Internal
Mev Dominguez-Valentin, Saskia Haupt, Toni T. Seppaelae, Julian R. Sampson, Lone Sunde, Inge Bernstein, Mark A. Jenkins, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Francesc Balaguer, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Tadeusz Debniak, Robert Fruscio, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Lor H. Katz, Ido Laish, Elez Vainer, Carlos Vaccaro, Dirce Maria Carraro, Kevin Monahan, Elizabeth Half, Aine Stakelum, Des Winter, Rory Kennelly, Nathan Gluck, Harsh Sheth, Naim Abu-Freha, Marc Greenblatt, Benedito Mauro Rossi, Mabel Bohorquez, Giulia Martina Cavestro, Leonardo S. Lino-Silva, Karoline Horisberger, Maria Grazia Tibiletti, Ivana do Nascimento, Huw Thomas, Norma Teresa Rossi, Leandro Apolinario da Silva, Attila Zarand, Juan Ruiz-Banobre, Vincent Heuveline, Jukka-Pekka Mecklin, Kirsi Pylvaenaeinen, Laura Renkonen-Sinisalo, Anna Lepistoe, Paeivi Peltomaeki, Christina Therkildsen, Mia Gebauer Madsen, Stefan Kobbelgaard Burgdorf, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane Lindor, Steven Gallinge, Loic Le Marchand, Polly A. Newcomb, Jane Figueiredo, Daniel D. Buchanan, Stephen N. Thibodeau, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Evelin Schroeck, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hueneburg, Silke Redler, Reinhard Buettner, Jurgen Weitz, Marta Pineda, Nuria Duenas, Joan Brunet Vidal, Leticia Moreira, Ariadna Sanchez, Eivind Hovig, Sigve Nakken, Kate Green, Fiona Lalloo, James Hill, Emma Crosbie, Miriam Mints, Yael Goldberg, Douglas Tjandra, Sanne W. ten Broeke, Revital Kariv, Guy Rosner, Suresh H. Advani, Lidiya Thomas, Pankaj Shah, Mithun Shah, Florencia Neffa, Patricia Esperon, Walter Pavicic, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Alejandra Martin, Gabriela Moslein, Pal Moller
Summary: This study used the latest PLSD cohort to investigate the mortality rates and age of cancer diagnoses in carriers of pathogenic MMR variants. The results showed that non-colorectal Lynch syndrome cancers caused more deaths than colorectal cancers in these carriers. Reducing deaths from non-colorectal cancers is a crucial challenge for the medical care of Lynch syndrome.
Article
Oncology
Koldo Garcia-Etxebarria, Ane Etxart, Maialen Barrero, Beatriz Nafria, Nerea Miren Segues Merino, Irati Romero-Garmendia, Ajay Goel, Andre Franke, Mauro D'Amato, Luis Bujanda
Summary: This study found that some genetic polymorphisms (SNPs), when combined with clinical data, can be used as predictors for colorectal cancer (CRC) outcomes. Additionally, new SNPs associated with CRC outcomes were detected and may serve as feasible markers.
Article
Endocrinology & Metabolism
Francisco J. Osuna-Prieto, Huiwen Xu, Lourdes Ortiz-Alvarez, Xinyu Di, Isabelle Kohler, Lucas Jurado-Fasoli, Jose Rubio-Lopez, Julio Plaza-Diaz, Ramiro Vilchez-Vargas, Alexander Link, Angel Gil, Jonatan R. Ruiz, Patrick C. N. Rensen, Borja Martinez-Tellez
Summary: The study investigated the relationship between fecal microbiota diversity and composition and plasma bile acid levels in young adults. The results showed that fecal microbiota diversity and evenness, as well as the relative abundance of Firmicutes and Bacteroidetes phyla, were positively associated with plasma levels of secondary bile acids. However, further investigations are needed to confirm whether gut microbiota composition can regulate plasma bile acid concentrations in humans.