Publications by authors named "Kouya Shiraishi"

A germline alteration in the PTEN gene causes a spectrum of disorders conceptualized as PTEN hamartoma tumor syndrome (PHTS), which show high risk of tumor development and a highly variable and complex phenotype. The diagnosis of PHTS is established in a proband by identification of a heterozygous germline PTEN pathogenic variant on molecular genetic testing. In this study, to understand more PTEN-associated clinical phenotype and PHTS in a Japanese population, we extracted 128 germline PTEN rare variants from 113,535 adult Japanese registered in Biobank Japan (BBJ), and categorized 29 pathogenic/likely pathogenic variants in 30 individuals (0.

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Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.

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  • * Results showed that a higher PRS was more strongly related to EGFR-positive LUAD cases (OR=8.63) than to EGFR-negative cases (OR=3.50), indicating a significant association based on mutation status.
  • * These findings imply that genetic susceptibility to LUAD differs in never-smoking East Asian women depending on whether the cancer has specific mutations, which could affect public health strategies and clinical practices.*
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Purpose: Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined.

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  • * In a study of 1,112 patients with EOC, 12.8% were found to have HRR-related PVs, which were linked to more severe disease characteristics, including serous carcinoma and advanced stages.
  • * Patients with HRR-PV-positive status showed improved overall survival in later-stage disease, highlighting the need for genetic testing to tailor individual treatments, while the study also noted a limited use of certain therapies during the study period.
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The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion.

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Objective: The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging.

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  • * The newly developed multi-ancestry PRS showed a strong correlation with LUAD risk, indicating that individuals in the highest PRS percentile had significantly increased risk compared to those in the lowest.
  • * Findings suggest that those in the highest risk category have a lifetime risk of about 6.69%, and they reach the average population's 10-year risk for LUAD by age 41, highlighting the importance of multi-ancestry PRS for better risk assessment in this group.
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Background: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC.

Methods: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry.

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Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

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  • A study examined vulvar squamous cell carcinoma (VSCC) in Japanese patients to explore genomic profiles and racial differences, as this disease is rare and not well understood.
  • The research included 48 patients from two Japanese cancer centers, identifying TP53 as the most common mutation, followed by HRAS, CDKN2A, and PIK3CA, with mutation frequencies similar to Caucasian patients.
  • TP53 mutations were linked to poorer patient prognosis, suggesting the potential for targeted therapies based on these genomic findings.
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Objective: The efficacy of pembrolizumab in patients with microsatellite instability (MSI)-high cancers has been reported; however, the differences in efficacy according to the subtypes of MSI-high endometrial cancers (ECs) remain unclear. MSI-high ECs are classified into at least 3 groups based on their molecular characteristics: hypermethylated, Lynch-like syndrome (LLS)-associated, and Lynch syndrome (LS)-associated cancers. This study aimed to investigate whether the efficacy of pembrolizumab differs among these 3 groups, and if so, whether EPM2AIP1 immunohistochemistry (IHC), which correlates with promoter methylation, can be used to rule out methylation cases.

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Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a "disease flare.

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  • PD-L1 expression is a key factor in predicting the success of anti-PD-1/PD-L1 treatments in advanced lung cancer, but differences in assay results can complicate evaluations.
  • A study reviewed patients who had their PD-L1 status checked using two different assays and found that a significant number showed discrepancies, which correlated with lower treatment effectiveness in those receiving pembrolizumab.
  • The findings suggest that differences in PD-L1 assay results may indicate a specific resistance mechanism to treatments, highlighting the potential importance of understanding these discrepancies in clinical settings.
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  • The study investigated the clinical features and prognosis of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese endometrial cancer (EC) patients, involving targeted gene sequencing of LS-related genes in 443 diagnosed cases from 2011 to 2018.
  • Out of these patients, 3.7% had pathogenic gene variants, and 27% showed loss of at least one mismatch repair protein through immunohistochemistry.
  • Notably, patients with LS and MMR protein loss had a favorable 5-year overall survival rate of 100%, while those with sporadic MMRd and aberrant p53 expression had significantly lower survival rates, indicating p53 and MMR gene variants as
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  • DNA methylation is an important epigenetic modification that influences gene expression and is crucial for understanding development and cell differentiation.
  • Most existing analysis tools for DNA methylation focus on comparing data within a single dataset, making it hard to conduct cross-dataset studies like those for rare diseases.
  • The new methPLIER method allows for interdataset comparisons by utilizing advanced techniques such as non-negative matrix factorization and transfer learning, making it more versatile in analyzing methylation data across different studies and platforms.
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  • The study analyzed the age at lung cancer diagnosis and sex differences in individuals who never smoked, involving 33,793 participants from various regions including East Asia, the US, and the UK.
  • Results showed that in Chinese individuals, females were diagnosed at a younger age than males, with significant differences recorded in several locations, while patterns in other racial groups were inconsistent.
  • The findings suggest that there are notable sex differences in the age of diagnosis for lung cancer among non-smokers, highlighting the need for further research in this area.
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Introduction: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a group 1 carcinogen linked to lung cancer. However, in contrast to active smoking, the mutagenic properties of PS remain unclear.

Methods: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared.

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  • The study investigates the early stages of tumor development, specifically focusing on lung adenocarcinomas like adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma.
  • Researchers conducted comprehensive genomic analysis on 76 lung cancer samples, combining sequencing data with transcriptomic and epigenomic information.
  • Findings indicate that very early-stage tumors have minimal somatic mutations, primarily in key driver mutations, leading to copy number changes and global DNA hypomethylation as the disease progresses, particularly in Noguchi type B tumors.
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  • Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) has a high treatment failure rate and is characterized by gene fusions, particularly involving the PDGFRB gene.
  • Researchers identified a new PDGFRB fusion gene, NRIP1::PDGFRB, in a pediatric ALL patient, which encodes a protein with the kinase domain of PDGFRB but lacks the partner peptide.
  • The study confirmed that NRIP1::PDGFRB has oncogenic potential and can be effectively targeted by various ABL1-specific inhibitors like imatinib and dasatinib, highlighting a novel fusion gene pattern in Ph-like ALL.
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  • Molecular classification was integrated into endometrial cancer staging with the transition from FIGO 2008 to FIGO 2023, leading to changes in how certain types of the cancer are classified based on their molecular characteristics.
  • A study involving 265 patients compared the effectiveness of three staging systems (FIGO 2008, FIGO 2023 without molecular classification, and FIGO 2023 with molecular classification) using specific statistical measures to determine accuracy.
  • The results showed that FIGO 2023 had the best performance in terms of predictive accuracy, highlighting the significance of p53 status as a poor prognostic indicator, particularly in advanced stages of the disease.
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  • - The study investigates the role of Delta-like ligand 3 (DLL3) as a therapeutic target in small-cell lung cancer (SCLC) and its impact on the tumor microenvironment (TME) and patient outcomes.
  • - Results show that in limited-stage SCLC, DLL3 expression is associated with more neoantigens but reduced immune activity, leading to lower levels of immune cells like T cells and dendritic cells.
  • - In extensive-stage SCLC, patients with DLL3-expressing tumors experience significantly worse progression-free survival when treated with standard chemotherapy and anti-PD-L1 therapy, indicating resistance linked to suppressed immune responses.
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