Article
Oncology
Minna M. Jaaskelainen, Satu Tiainen, Hanna Siiskonen, Maarit Ahtiainen, Teijo Kuopio, Aino Ronka, Tiia Kettunen, Kirsi Hamalinen, Kirsi Rilla, Ilkka Harvima, Arto Mannermaa, Paivi Auvinen
Summary: In HER2-positive breast cancer patients, the levels of regulatory TILs and cytotoxic TILs, as well as the presence of TAMs, are associated with the efficacy of trastuzumab and patient outcomes. High levels of regulatory TILs are associated with shorter disease-free survival, while a high ratio of cytotoxic TILs to TAMs is associated with significant benefit from adjuvant trastuzumab.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Multidisciplinary Sciences
Stephanie Cabarcas-Petroski, Gabriella Olshefsky, Laura Schramm
Summary: This study analyzed breast cancer datasets and found amplification of MAF1 in breast cancer, which is associated with other genes. MAF1 expression is significantly increased in HER2-positive breast cancer and is related to the prognosis of trastuzumab treatment.
Article
Oncology
Jenny Pousette, Annelie Johansson, Carolin Jonsson, Tommy Fornander, Linda S. Lindstrom, Hans Olsson, Gizeh Perez-Tenorio
Summary: The presence of immune cells within the tumor (TILs) does not have prognostic value for hormone-responsive breast cancer (ER+/HER2-). However, high expression of certain TIL markers indicates good prognosis and may be used for immunotherapy interventions after tamoxifen failure for ER+/HER2- subtype.
Article
Oncology
Aiko Sueta, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Yoshitaka Fujiki, Lisa Goto-Yamaguchi, Hirotaka Iwase, Yutaka Yamamoto
Summary: This study aimed to evaluate the prognostic value of BRCAness in HER2-negative breast cancer patients who received NAC treatment. The results showed that post-treatment BRCA1-like phenotype was a significant prognostic factor, while pre-treatment BRCA1-like phenotype was not associated with prognosis. Among non-pCR patients, 19% of patients had a change in phenotype during NAC treatment.
Article
Multidisciplinary Sciences
Young-Joon Kang, Se Jeong Oh, Soo Youn Bae, Eun-Kyu Kim, Young-Jin Lee, Eun Hwa Park, Joon Jeong, Heung Kyu Park, Young Jin Suh, Yong-Seok Kim
Summary: This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. It found that age, advanced tumor and lymph node stage, high histological grade, presence of lymphatic and vascular invasion, and hormone receptor-negative status were associated with poor overall survival. Node status had a more significant relationship with long-term prognosis than tumor stage in HER2-positive breast cancer patients.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Francesca Ligorio, Serena Di Cosimo, Paolo Verderio, Chiara Maura Ciniselli, Sara Pizzamiglio, Lorenzo Castagnoli, Matteo Dugo, Barbara Galbardi, Roberto Salgado, Sherene Loi, Stefan Michiels, Tiziana Triulzi, Elda Tagliabue, Sarra El-Abed, Miguel Izquierdo, Evandro de Azambuja, Paolo Nuciforo, Jens Huober, Luca Moscetti, Wolfgang Janni, Maria Antonia Coccia-Portugal, Paola Antonia Corsetto, Antonino Belfiore, Daniele Lorenzini, Maria Grazia Daidone, Andrea Vingiani, Luca Gianni, Serenella Maria Pupa, Giampaolo Bianchini, Giancarlo Pruneri, Claudio Vernieri
Summary: This study found that high expression of CD36 is associated with worse clinical outcomes in early-stage HER2+ BC patients treated with anti-HER2 therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Multidisciplinary Sciences
Alma Andersson, Ludvig Larsson, Linnea Stenbeck, Fredrik Salmen, Anna Ehinger, Sunny Z. Wu, Ghamdan Al-Eryani, Daniel Roden, Alex Swarbrick, Ake Borg, Jonas Frisen, Camilla Engblom, Joakim Lundeberg
Summary: This study utilized Spatial Transcriptomics technology to investigate gene expression in HER2-positive breast tumors, identifying shared gene signatures for immune and tumor processes and developing a predictive model for cellular interactions.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Santiago Duro-Sanchez, Macarena Roman Alonso, Joaquin Arribas
Summary: A variety of treatments are available for HER2-positive breast cancer, but resistance to these therapies is common and associated with poor prognosis. Immunotherapeutic approaches are being explored to eradicate tumor cells and prevent relapse and progression. This review discusses the different immunotherapeutic strategies being tested and their potential benefits for HER2-positive breast cancer.
Article
Oncology
Long Wang, Xue Zhang, Mengxue Wang, Yunhai Li, Jiali Xu, Jiaying Wei, Hongzhong Li, Guosheng Ren, Xuedong Yin
Summary: By analyzing the ImmuneScore and StromalScore, differentially expressed genes, and performing immunohistochemical analyses, it was found that AMPD1 could serve as a novel biomarker for predicting the immune response and disease outcome in HER2+ BC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Sofia Bruni, Florencia L. Mauro, Cecilia J. Proietti, Rosalia Cordo-Russo, Martin A. Rivas, Gloria Inurrigarro, Agustina Dupont, Dario Rocha, Elmer A. Fernandez, Ernesto Gil Deza, Daniel Lopez Della Vecchia, Sabrina Barchuk, Silvina Figurelli, David Lasso, Adrian D. Friedrich, Maria C. Santilli, Maria Regge, Gabriel Lebersztein, Claudio Levit, Fabiana Anfuso, Teresa Castiglione, Patricia Elizalde, Maria F. Mercogliano, Roxana Schillaci
Summary: This study reveals the involvement of MUC4 in hindering the therapeutic effect of trastuzumab in HER2+ breast cancer. By inhibiting TNF alpha, MUC4 expression is decreased and the antitumor effect of trastuzumab is improved.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Yu Kou, Zhuoqun Li, Qidi Sun, Shengnan Yang, Yunshuai Wang, Chen Hu, Huijie Gu, Huangjian Wang, Hairong Xu, Yan Li, Baowei Han
Summary: This study investigated the roles of different subtypes of tumour-associated macrophages (TAMs) as prognostic and predictive biomarkers for colorectal cancer (CRC). The results showed that high expressions of CD86(+) and CD68(+)CD86(+) TAMs as well as low expression of CD163(+) and CD68(+)CD163(+) TAMs were significantly associated with favourable overall survival (OS). In addition, CD86 protein expression negatively correlated with tumour differentiation and TNM stage, while CD163 protein expression positively correlated with tumour differentiation and size.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Chundi Gao, Huayao Li, Chao Zhou, Cun Liu, Jing Zhuang, Lijuan Liu, Changgang Sun
Summary: Using bioinformatics techniques, this study identified differentially expressed metabolic genes in patients with HER2-positive breast cancer and triple-negative breast cancer. Specific transcriptional changes in metabolism-related genes were found to be biomarkers for predicting patient prognosis, and a risk scoring system based on these genes showed higher predictive sensitivity than other clinical factors.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Zhenzhen Liu, Chengzheng Wang, Xiuchun Chen, Jiujun Zhu, Xianfu Sun, Qingxin Xia, Zhenduo Lu, Jianghua Qiao, Yong Zhou, Haixue Wang, Yi Wang, Min Yan
Summary: This study evaluated the efficacy of pyrotinib plus trastuzumab, docetaxel, and carboplatin as neoadjuvant therapy for early breast cancer and explored the predictive role of immune cell subpopulations. The results showed promising efficacy and manageable toxicity of this treatment regimen. The study also found that the immune microenvironment may play an important role in the response to neoadjuvant pyrotinib-based therapy.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Zhongwei Li, Pengfei Wang, Wenjie Cui, Hongmei Yong, Diandian Wang, Tiesuo Zhao, Wenwen Wang, Ming Shi, Junnian Zheng, Jin Bai
Summary: The study found that DNMT1 is overexpressed in breast cancer and promotes tumorigenesis and metastasis by activating its expression through ZEB1 and P300, and increasing its expression through the IL-6-pSTAT3-ZEB1-DNMT1 axis in the tumor microenvironment.
CELL AND BIOSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Francesca Sanguedolce, Magda Zanelli, Andrea Palicelli, Alessandra Bisagni, Maurizio Zizzo, Stefano Ascani, Maria Carmela Pedicillo, Angelo Cormio, Ugo Giovanni Falagario, Giuseppe Carrieri, Luigi Cormio
Summary: Bladder cancer is a heterogeneous disease with molecular, morphological, and clinical variations. HER2 is an oncogene involved in the development of bladder cancer. Assessing HER2 overexpression through immunohistochemistry can be useful in correctly identifying different types of bladder lesions, providing prognostic information, and improving BC molecular subtyping. Additionally, HER2 has potential as a therapeutic target in the development of novel target therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hannah L. Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S. Winter, Kevin S. Kapner, Scott P. Ginebaugh, Sara A. Vayrynen, Juha P. Vayrynen, Chen Yuan, Andrew W. Navia, Junning Wang, Annan Yang, Timothy L. Bosse, Radha L. Kalekar, Kristen E. Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A. Rubinson, Harshabad Singh, Kimberly Perez, James M. Cleary, Thomas E. Clancy, Jiping Wang, Joseph D. Mancias, Lauren K. Brais, Emma R. Hill, Margaret M. Kozak, David C. Linehan, Richard F. Dunne, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, William C. Hahn, Alex K. Shalek, Andrew J. Aguirre, Jonathan A. Nowak, Brian M. Wolpin
Summary: A multiplex immunofluorescence (mIF) pipeline was developed to investigate the protein expression and intratumoral heterogeneity of pancreatic ductal adenocarcinoma (PDAC). The results showed that PDAC tumors exhibit extensive intratumoral heterogeneity, which is associated with patient outcomes and can be reduced in patient-derived organoid cultures. Co-expressor cells expressing both classical and basal markers were found in the majority of tumors, suggesting an intermediate state between subtype poles. This clinically applicable pipeline has implications for prognosis and treatment selection in PDAC patients.
Article
Oncology
Mehrdad Rakaee, Elio Adib, Biagio Ricciuti, Lynette M. Sholl, Weiwei Shi, Joao Alessi, Alessio Cortellini, Claudia A. M. Fulgenzi, Patrizia Viola, David J. Pinato, Sayed Hashemi, Idris Bahce, Ilias Houda, Ezgi B. Ulas, Teodora Radonic, Juha P. Vayrynen, Elin Richardsen, Simin Jamaly, Sigve Andersen, Tom Donnem, Mark M. Awad, David J. Kwiatkowski
Summary: This study developed a machine-learning-based approach to evaluate the association between tumor-infiltrating lymphocytes (TILs) and immune checkpoint inhibitor (ICI) therapy in lung cancer patients. The results showed that high levels of TILs were associated with ICI treatment response and could be used for patient selection and precision therapy guidance.
Article
Oncology
Topias Karjula, Hanna Elomaa, Anne Niskakangas, Olli Mustonen, Iiris Puro, Teijo Kuopio, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The study found that CD3(+) and CD8(+) T-cell density and PD-1/PD-L1 expression have prognostic value in pulmonary metastases of colorectal cancer. T-cell infiltration is higher in pulmonary metastases compared to primary tumors. High CD3(+) and CD8(+) cell density are associated with better survival, while high PD-L1 expression is associated with favorable prognosis.
Article
Oncology
Meeri Kastinen, Paeivi Sirnio, Hanna Elomaa, Maarit Ahtiainen, Sara A. Vayrynen, Karl-Heinz Herzig, Sanna Merilainen, Raila Aro, Reetta Haivala, Tero Rautio, Juha Saarnio, Erkki-Ville Wirta, Olli Helminen, Toni T. Seppala, Teijo Kuopio, Jan Bohm, Anne Tuomisto, Jukka-Pekka Mecklin, Markus J. Makinen, Juha P. Vayrynen
Summary: This study analyzed data from 1413 patients with colorectal cancer and found associations between tumor necrosis percentage and tumor characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis. The results showed that high tumor necrosis percentage is associated with shorter colorectal cancer-specific survival, independent of other factors. Tumor necrosis is therefore considered an important prognostic factor in colorectal cancer.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Hanna Elomaa, Maarit Ahtiainen, Sara A. Vaeyrynen, Shuji Ogino, Jonathan A. Nowak, Mai Chan Lau, Olli Helminen, Erkki-Ville Wirta, Toni T. Seppaelae, Jan Boehm, Jukka-Pekka Mecklin, Teijo Kuopio, Juha P. Vaeyrynen
Summary: The expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. This study found that PD-L1(+) macrophages and PD-1(+) T cells were associated with better clinical outcomes in colorectal cancer patients. These findings enhance the understanding of immune checkpoints in the tumor microenvironment and could contribute to the development of improved immunotherapies.
BRITISH JOURNAL OF CANCER
(2023)
Letter
Hematology
Tero Vuolio, Outi Kuittinen, Juha P. Vayrynen, Hanna-Riikka Teppo, Roosa E. I. Prusil, Maria Ramet, Hanne Kuitunen, Timo Paloneva, Milla E. L. Kuusisto
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Liisa Petainen, Juha P. Vayrynen, Pekka Ruusuvuori, Ilkka Polonen, Sami Ayramo, Teijo Kuopio
Summary: This study proposes an automated method for estimating tumor-stroma ratio (TSR) from histopathological images of colorectal cancer using convolutional neural networks. The models achieved high accuracy in classifying stroma, tumor, and other tissues, with the best model reaching 99.3% accuracy for tumor classification. The predicted TSR values showed moderate correlation with pathologist estimations (0.57).
Article
Pathology
Topias Karjula, Anne Niskakangas, Olli Mustonen, Iiris Puro, Hanna Elomaa, Maarit Ahtiainen, Teijo Kuopio, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Fredrik Yannopoulos, Olli Helminen, Juha P. Vayrynen
Summary: In this study, the prognostic effect of tertiary lymphoid structures (TLSs) on colorectal cancer (CRC) pulmonary metastases and primary tumors was analyzed. The density and diameter of TLSs showed no prognostic value in pulmonary metastases, but higher density and diameter were associated with lower mortality in primary tumors.
Article
Multidisciplinary Sciences
Pei-Chen Tsai, Tsung-Hua Lee, Kun-Chi Kuo, Fang-Yi Su, Tsung-Lu Michael Lee, Eliana Marostica, Tomotaka Ugai, Melissa Zhao, Mai Chan Lau, Juha P. Vayrynen, Marios Giannakis, Yasutoshi Takashima, Seyed Mousavi Kahaki, Kana Wu, Mingyang Song, Jeffrey A. Meyerhardt, Andrew T. Chan, Jung-Hsien Chiang, Jonathan Nowak, Shuji Ogino, Kun-Hsing Yu
Summary: The authors develop a machine learning-based platform, MOMA, to systematically identify and interpret the relationship between patients' histologic patterns, multi-omics, and clinical profiles. MOMA successfully predicts the overall survival, disease-free survival, and copy number alterations of colorectal cancer patients. Additionally, MOMA identifies interpretable pathology patterns predictive of gene expression profiles, microsatellite instability status, and clinically actionable genetic alterations.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jouni Harkonen, Petri Polonen, Ashik Jawahar Deen, Ilakya Selvarajan, Hanna-Riikka Teppo, Elitsa Y. Dimova, Thomas Kietzmann, Maarit Ahtiainen, Juha P. Vayrynen, Sara A. Vayrynen, Hanna Elomaa, Niko Tynkkynen, Tiia Eklund, Teijo Kuopio, Eva-Maria Talvitie, Pekka Taimen, Markku Kallajoki, Minna U. Kaikkonen, Merja Heinaniemi, Anna-Liisa Levonen
Summary: The NRF2 pathway is frequently activated in various cancer types, but a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and conducted a pan-cancer analysis of oncogenic NRF2 signaling using it. Our findings revealed an immunoevasive phenotype in squamous malignancies of the lung, head and neck area, cervix, and esophagus, where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression, and T cell and macrophage infiltration. These tumors have a molecular phenotype with amplification of SOX2/TP63, TP53 mutation, and CDKN2A loss, and are associated with upregulation of immunomodulatory genes NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1, and PD-L1. Our functional genomics analyses suggest that these genes are candidate NRF2 targets, indicating a direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands and increased expression of immunosuppressive ligands NAMPT, SPP1, and WNT5A involved in intercellular crosstalk. Moreover, the negative relationship between NRF2 and immune cells is explained by stromal populations of lung squamous cell carcinoma, indicating a potential effect across multiple squamous malignancies based on our molecular subtyping and deconvolution data.
Article
Oncology
Melissa Zhao, Mai Chan Lau, Koichiro Haruki, Juha P. Vayrynen, Carino Gurjao, Sara A. Vayrynen, Andressa Dias Costa, Jennifer Borowsky, Kenji Fujiyoshi, Kota Arima, Tsuyoshi Hamada, Jochen K. Lennerz, Charles S. Fuchs, Reiko Nishihara, Andrew T. Chan, Kimmie Ng, Xuehong Zhang, Jeffrey A. Meyerhardt, Mingyang Song, Molin Wang, Marios Giannakis, Jonathan A. Nowak, Kun-Hsing Yu, Tomotaka Ugai, Shuji Ogino
Summary: By using Bayesian additive regression trees (BART), a statistical learning technique, the study aimed to improve the prediction of prognosis for colorectal cancer by comprehensively analyzing patient-specific tumor characteristics. The BART risk model identified seven stable survival predictors and the risk stratifications based on model-predicted survival were statistically significant. BART demonstrated flexibility, interpretability, and comparable or superior performance to other machine-learning models, making it a valuable tool for prognostic stratifications in colorectal cancer patients.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Tiia J. Honkanen, Milla E. K. Luukkainen, Jussi P. Koivunen
Summary: This study investigated the role of HER3 in ALK TKI resistance in ALK+ NSCLC. The results showed that combined targeting of ALK and ERBB resulted in significant inhibition of colony formation and downregulation of pAKT levels. HER3 knockdown led to downregulation of ALK expression and visible morphological changes in ALK+ cell lines. Co-immunoprecipitation and proximity ligation assay experiments confirmed the interaction between ALK and HER3 in vitro and in ALK+ NSCLC tumor samples.
CANCER BIOLOGY & THERAPY
(2023)
Article
Respiratory System
Topias Karjula, Anne Niskakangas, Olli Mustonen, Iiris Puro, Juha P. Vayrynen, Olli Helminen, Fredrik Yannopoulos
Summary: A considerable proportion of intended pulmonary metastasectomies turn out as new incidental primary lung cancers. The study highlights the diagnostic importance of pulmonary metastasectomy and suggests segmentectomy as a primary procedure for patients with a long disease-free interval and a heavy smoking history.
JOURNAL OF THORACIC DISEASE
(2023)
Article
Oncology
Otto Manninen, Laura Puuniemi, Sanna Iivanainen, Martti Arffman, Riitta Kaarteenaho, Jussi Koivunen
Summary: In this study, it was found that EGFR mutants treated with afatinib had improved outcomes compared to gefitinib, with around 20% of patients receiving later-line osimertinib treatment after gefitinib or afatinib. The study highlights the real-world performance of EGFR TKIs and provides insights into therapy sequencing.
Article
Oncology
Anna Jokimaki, Sanna Iivanainen, Raija Mikkonen, Kallio Mika, Jussi Koivunen
Summary: This study evaluated the feasibility of a point-of-care device in the early detection of chemotherapy-induced peripheral neuropathy (CIPN). The results showed that the device had a high rate of measurement failure in some patients, especially those with a high risk of neuropathy.