University of the Ryukyus · Faculty of Medicine · 助教

Research keywordspelvic organ prolapse・genome wide association study・renal cell carcinoma biomarkers・prostate cancer markers・MUC1 expression・LOXL polymorphisms

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• Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma2024 · BACKGROUND: Currently, no useful serum markers exist for clear cell renal cell carcinoma (ccRCC), making early detection challenging as diagnosis relies solely on imaging tests. Radiation exposure is also a concern due to multiple required CT examinations during treatment. Renal cell carcinoma (RCC) histological types include ccRCC and non-clear cell RCC (non-ccRCC); however, treatment response to medications varies which necessitates accurate differentiation between the two. Therefore, we aimed to identify a novel serum marker of RCC. Increased LRG1 expression in the serum has been demonstrated in multiple cancer types. However, the expression of LRG1 expression in the serum and cancer tissues of patients with RCC has not been reported. Since ccRCC is a hypervascular tumor and LRG1 is capable of accelerating angiogenesis, we hypothesized that the LRG1 levels may be related to ccRCC. Therefore, we examined LRG1 expression in sera from patients with RCC. METHODS: Using an enzyme-linked immunosorbent assay, serum levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) were measured in 64 patients with ccRCC and 22 patients non-ccRCC who underwent radical or partial nephrectomy, as well as in 63 patients without cancer. RESULTS: Median values of serum LRG1 and their inter-quartile ranges were 63.2 (42.8-94.2) µg/mL in ccRCC, 23.4 (17.7-29.6) µg/mL in non-ccRCC, and 36.0 (23.7-56.7) µg/mL in patients without cancer, respectively (ccRCC vs. non-ccRCC or patients without cancer: P < 0.001). C-reactive protein (CRP) levels (P = 0.002), anemia (P = 0.037), hypercalcemia (P = 0.023), and grade (P = 0.031) were independent predictors of serum LRG1 levels in ccRCC. To assess diagnostic performance, the area under the receiver operating characteristic curve of serum LRG1 was utilized to differentiate ccRCC from non-cancer and non-ccRCC, with values of 0.73 (95% CI, 0.64-0.82) and 0.91 (95% CI, 0.82-0.96), respectively. CONCLUSIONS: LRG1 served as a serum marker associated with inflammation, indicated by CRP, anemia, hypercalcemia, and malignant potential in ccRCC. Clinically, serum LRG1 levels may assist in differentiating ccRCC from non-ccRCC with excellent diagnostic accuracy.
• MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration-resistant prostate cancer2024 · Nakanishi, S; Suda, T; Tanaka, K; Yonamine, T; Numahata, K; Sugawa, A; Oshiro, T; Oshiro, Y; Saito, S; Inokuchi, J
• Genome-wide association studies for pelvic organ prolapse in the Japanese population2024 · Pelvic organ prolapse (POP) affects approximately 40% of elderly women, characterized by thedescent of the pelvic organs into the vaginal cavity. Here we present the results of a genome-wideassociation study (GWAS) for susceptibility to POP comprising 771 cases and 76,625 controls in theJapanese population. We identified a significant association of WT1 locus with POP in the Japanesepopulation; rs10742277; odds ratio (OR) = 1.48, 95% confidence interval (CI), 1.29–1.68,P = 6.72 × 10−9. Subsequent cross-ancestry GWAS meta-analysis combining the Japanese data andpreviously reported European data, including 28,857 cases and 622,916 controls, identified FGFR2locus as a novel susceptibility locus to POP (rs7072877; OR = 1.06, 95% CI, 1.04–1.08,P = 4.11 × 10−8). We also observed consistent directions of the effects for 21 out of 24 European GWASderived loci (binomial test P = 2.8 × 10−4), indicating that most of susceptibility loci for POP are sharedacross the Japanese and European populations.
• Stage-specific Embryogenic Antigen-4 Expression in Castration-resistant Prostate Cancer and its Correlation With the Androgen Receptor.2021 · Harada J, Miyata Y, Taima T, Matsuda T, Mukae Y, Mitsunari K, Matsuo T, Ohba K, Suda T, Sakai H, Ito A, Saito S

• 前立腺癌の悪性度に関わる幹細胞マーカーSSEA-4の役割2020 · 基盤研究(C)
• 高悪性度の前立腺癌に発現するマーカーの研究2016 · 前立腺癌の悪性度に関連する分子として、酵素蛋白PCGP-enz、解糖系関連蛋白PCGP-glyco、血圧関連分子PCGP-bp、ストレス応答分子PCGP-stress、ユビキチン関連蛋白PCGP-ub、高悪性度乳がんに共通発現する蛋白PCGP-br、肺癌にも発現する蛋白PCGP-lc、ER蛋白PCGP-er、等々を同定した。これらの分子のうち、PCGP-lcの高発現群は低発現群に比して、有意にGleason score (GS)が高かった。また、PCGP-erに関しては、高発現群は低発現群に比して有意にGSが高く、T stageも高かった。またSSEA-4が前立腺癌の悪性度に関連していた。
• 高悪性度の前立腺癌に発現するマーカーの研究2016 · 前立腺癌の悪性度に関連する分子として、酵素蛋白PCGP-enz、解糖系関連蛋白PCGP-glyco、血圧関連分子PCGP-bp、ストレス応答分子PCGP-stress、ユビキチン関連蛋白PCGP-ub、高悪性度乳がんに共通発現する蛋白PCGP-br、肺癌にも発現する蛋白PCGP-lc、ER蛋白PCGP-er、等々を同定した。これらの分子のうち、PCGP-lcの高発現群は低発現群に比して、有意にGleason score (GS)が高かった。また、PCGP-erに関しては、高発現群は低発現群に比して有意にGSが高く、T stageも高かった。またSSEA-4が前立腺癌の悪性度に関連していた。
• 糖鎖抗原ＲＭ２に基づく糖蛋白を指標とした新規前立腺癌診断マーカーの探索2014 · 前立腺癌の糖鎖抗原RM2は、免疫組織学的解析の結果、前立腺癌特異的で悪性度を反映し、新しいマーカーとなり得る。しかし、この抗原を持つ前立腺癌特異的な糖蛋白は未だ明らかとなっていない。我々は、RM2抗体が強く認識する50kDaの糖蛋白を中心にアミノ酸解析を行い、各標的蛋白の診断マーカーとしての有用性を解析した。前立腺癌の免疫組織学的解析により、この標的蛋白はグリーソンスコアと相関し、悪性度を反映した。また、その他の臨床病理学的所見とも相関し、診断補助因子となり得ることが示唆された。標的糖蛋白の一つは、前立腺癌患者において尿中蛋白量が減少し、体外診断マーカーとなり得ることが示唆された。

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