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• MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration‑resistant prostate cancer

  Nakanishi Shotaro, Suda Tetsuji, Tanaka Kei, Yonamine Tomoko, Numahata Kenji, Sugawa Ai, Oshiro Takuma, Oshiro Yoshinori, Saito Seiichi, Inokuchi Junichi

  Glycoconjugate Journal ( Springer )  41   381 - 394   2024年12月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC). However, monitoring the progression status of AR-negative prostate cancer is a challenge because it does not produce prostate-specific antigen. Based on the negative relationship of expression between AR and SSEA-4, we hypothesized that a soluble molecule synchronized with SSEA-4 in expression could be a serum marker candidate for AR-negative prostate cancer. Thus, we investigated the molecular background of SSEA-4 expression by ST3GAL2-knockout in DU145 cells. Here we show that MUC1 is identified as a molecule associated with ST3GAL2 and expressed in AR-negative prostate cancer. A negative correlation of expression between AR and MUC1 was observed in prostate cancer cell lines and CRPC tissues. The average rate of MUC1 expression was nearly 60% in AR-negative prostate cancer cells in CRPC tissues. Level of serum CA15–3 (MUC1) was the highest in mCRPC among various stages and its higher level was associated with faster progression of mCRPC. Our results demonstrate that MUC1 is identified as a ST3GAL2-associated molecule and expressed in AR-negative CRPC cells. Furthermore, level of serum CA15–3 may reflect the progression status of mCRPC.

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    CiNii Research

• MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration-resistant prostate cancer

  Nakanishi, S; Suda, T; Tanaka, K; Yonamine, T; Numahata, K; Sugawa, A; Oshiro, T; Oshiro, Y; Saito, S; Inokuchi, J

  GLYCOCONJUGATE JOURNAL ( Glycoconjugate Journal )  41 ( 6 ) 381 - 394   2024年12月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

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    DOI
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• Genome-wide association studies for pelvic organ prolapse in the Japanese population

  Matsunami, M; Imamura, M; Ashikari, A; Liu, XX; Tomizuka, K; Hikino, K; Miwa, K; Kadekawa, K; Suda, T; Matsuda, K; Miyazato, M; Terao, C; Maeda, S

  COMMUNICATIONS BIOLOGY ( Nature Research )  7 ( 1 ) 1188 - 9   2024年09月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  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.

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• Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma

  Nakanishi, S; Goya, M; Suda, T; Yonamine, T; Sugawa, A; Saito, S

  BMC UROLOGY ( BMC Urology )  24 ( 1 ) 94 - 94   2024年04月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  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.

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• Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma

  Nakanishi Shotaro, Goya Masato, Suda Tetsuji, Yonamine Tomoko, Sugawa Ai, Saito Seiichi

  BMC Urology ( BioMed Central )  24   1 - 7   2024年04月 [ 査読有り ]

  掲載種別: 研究論文（学術雑誌）

  　概要を見る

  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.

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    CiNii Research

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• 前立腺癌の悪性度に関わる幹細胞マーカーSSEA-4の役割

  基盤研究(C)

  課題番号: 20K09581

  研究期間: 2020年04月  -  2023年03月 

  代表者: 須田 哲司  研究分担者: 齋藤 誠一

  直接経費: 3,400,000（円）  間接経費: 1,020,000（円）  金額合計: 4,420,000（円）

• 前立腺癌の悪性度に関わる幹細胞マーカーSSEA-4の役割

  基盤研究(C)

  課題番号: 20K09581

  研究期間: 2020年04月  -  2023年03月 

  代表者: 須田 哲司, 齋藤 誠一 

  直接経費: 3,400,000（円）  間接経費: 4,420,000（円）  金額合計: 1,020,000（円）

• 高悪性度の前立腺癌に発現するマーカーの研究

  基盤研究(C)

  課題番号: 16K11016

  研究期間: 2016年04月  -  2019年03月 

  代表者: 斎藤 誠一  研究分担者: 須田 哲司, 仲西 昌太郎, 呉屋 真人, 宮田 康好

  直接経費: 3,700,000（円）  間接経費: 1,110,000（円）  金額合計: 4,810,000（円）

  　概要を見る

  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

  基盤研究(C)

  課題番号: 16K11016

  研究期間: 2016年04月  -  2019年03月 

  代表者: 齋藤 誠一, 須田 哲司, 仲西 昌太郎, 呉屋 真人, 宮田 康好 

  直接経費: 3,700,000（円）  間接経費: 4,810,000（円）  金額合計: 1,110,000（円）

  　概要を見る

  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

  若手研究(B)

  課題番号: 26861277

  研究期間: 2014年04月  -  2017年03月 

  代表者: 須田 哲司  研究分担者: 斎藤 誠一, 仲西 昌太郎

  直接経費: 2,900,000（円）  間接経費: 870,000（円）  金額合計: 3,770,000（円）

  　概要を見る

  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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