Biomedical subjects

Ryuji Hamamoto

Publications and source records attributed to Ryuji Hamamoto.

3 recordsLinked to original sources

PubMed2026

Proteomic Analysis Identifies Potential Biomarkers of ELOC -Mutated Renal Cell Carcinoma.

ELOC -mutated renal cell carcinoma (RCC) is a rare tumor with only ∼40 cases reported to date; it shares a molecular background with clear cell RCC (ccRCC) in terms of hypoxia-inducible factor-alpha (HIF-α) protein accumulation. ELOC -mutated RCC is characterized by prominent leiomyomatous stromal growth and a more indolent clinical course compared with ccRCC. In our previous study, whole-genome sequencing of 102 ccRCC cases identified 5 cases of ELOC -mutated RCC. In the present study, we conducted proteomic and immunohistochemical analyses on up to 13 Japanese ELOC -mutated RCCs, including 8 previously reported cases, to elucidate its distinct molecular mechanisms and identify biomarkers that may be useful in distinguishing ELOC -mutated RCC from ccRCC. Proteomic profiling revealed that molecules, including cytokeratin 7, scinderin (SCIN), and sortilin 1 (SORT1), were significantly overexpressed in ELOC -mutated RCC compared with ccRCC. Notably, SCIN and SORT1 emerged as novel potential diagnostic biomarkers for distinguishing ELOC -mutated RCC from ccRCC. The analysis further suggested that ELOC -mutated RCC relies more on oxidative phosphorylation and less on glycolysis than ccRCC. This metabolic shift may be linked to the relative depletion of NAD+ due to the low expression of NAPRT and QPRT. In addition, we observed geographic variation in the disease frequency among different cohorts, with a higher frequency in Japan. Our findings provide novel insights into the pathogenesis of ELOC -mutated RCC and highlight SCIN and SORT1 as potential supportive biomarkers.

Humans↗

PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

PubMed2025

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

BACKGROUND: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear. PATIENTS AND METHODS: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD. The patients were classified into low or high EGFR-exp groups based on the median transcripts per million. We retrospectively examined the association between EGFR-exp, genomic characteristics, downstream EGFR signaling activity, tumor microenvironment (TME) status, and clinical outcomes. RESULTS: This study included 450 and 45 patients in the early- and advanced-stage cohorts, respectively. In both cohorts, the EGFR-exp low group exhibited a lower incidence of TP53 co-mutations and EGFR amplification and a higher incidence of EGFR subclonal mutations than the EGFR-exp high group. Furthermore, downstream EGFR signaling pathways, such as the MAPK signaling, were less activated in the EGFR-exp low group. However, this group showed significantly enriched adaptive immune response pathways (Q < 0.0001) and an immune-inflamed TME. Additionally, a low EGFR-exp was a significantly favorable factor for postoperative relapse (odds ratio [OR], 0.6; P = 0.04). However, in the advanced-stage cohort, a low EGFR-exp was a significant risk factor for non-responders to osimertinib (OR, 17.5; P = 0.03). CONCLUSIONS: In EGFRm LUAD, significant associations were observed between EGFR-exp levels and both EGFR signaling pathways and adaptive immune status, which in turn influence clinical outcomes. This large-scale multi-omics analysis highlights the heterogeneity among patients with EGFRm LUAD and emphasizes the need to assess EGFR-exp levels alongside mutation status for optimal treatment strategies in EGFRm LUAD.

Humans↗