Diagnostic and Prognostic Values of a Branched-chain Amino Acid-associated Gene Signature in Lung Cancer
分岐鎖アミノ酸関連遺伝子シグネチャーの肺癌における診断的および予後的価値 (機械翻訳の邦題)
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- 2026/08/17
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- 2026/08/03
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状態の根拠を見る →日本語要約(機械生成)
肺癌は世界で最も罹患率・死亡率の高い悪性腫瘍である。本研究では、分岐鎖アミノ酸(BCAA)関連遺伝子の予後シグネチャーを構築し、非小細胞肺癌(NSCLC)患者の臨床治療における有用性を検証した。TCGAコホートからBCAA関連候補遺伝子を差次的発現解析で選出し、肺腺癌(LUAD)と肺扁平上皮癌(LUSC)のデータセットを訓練・テストセットに分割した。訓練セット(366サンプル)で単変量Cox解析とLASSO Cox回帰を用いて6つの生存関連遺伝子(CAV1、GRIA1、LDHA、AOX1、GRIN2D、AKR1C1)を同定し、リスクモデルを構築した。患者を高リスク群と低リスク群に分け、シグネチャーは良好な診断・予後能を示した。キャリブレーション曲線とノモグラムにより予後シグネチャーの能力が確認された。本研究は、予後予測能と診断能を兼ね備えた初のBCAA関連シグネチャーであり、BCAA発現が将来の癌臨床治療における強力な潜在マーカーとなる可能性が示唆された。
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Background: : Lung cancer is the malignancy with the highest morbidity and mortality worldwide. Several studies have indicated that branched-chain amino acids (BCAAs) can regulate cancer progression and metabolism. In this study, a BCAA-associated prognostic signature was established and assessed to verify whether it can be used in clinical treatment of patients with non-small-cell lung carcinoma (NSCLC).MethodsThe candidate BCAA-associated genes were screened from TCGA cohort by differential expression analysis. Two datasets, the training and test sets, were divided from the lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and LUSC-only datasets in TCGA cohort and the novel model were constructed based on the training dataset. Moreover, all prognosis-related genes were screened via univariate Cox analysis. The LASSO Cox method was used to avoid collinearity. To further probe the clinical effect, a large number of clinical characteristics were included in the prognostic risk model. The outcomes for the calibration curves and nomogram proved the capability of the prognostic signature.ResultsBased on the 366 samples in the training set, six survival-related genes (CAV1, GRIA1, LDHA, AOX1, GRIN2D, and AKR1C1) were screened using the LASSO Cox regression analysis. Patients were divided into high- and low-risk groups. The signature demonstrated good diagnostic and prognostic capabilities.ConclusionWe developed the first-ever BCAA-related signature with both prognostic predictive power and diagnostic efficacy. The prognostic signature and diagnostic model suggested that the expression of BCAAs could serve as a powerful potential marker in cancer clinical treatment in the future.
DOI 10.21203/rs.3.rs-907919/v1
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