探究乳腺癌组织中尿素循环关键分子及其与乳腺癌临床病理特征和预后的关系。首先，通过TCGA及GTEx数据库筛选乳腺癌中差异表达的尿素循环关键分子，分析其与乳腺癌患者预后的关系。然后，收集2010年11月至2016年12月在西京医院进行手术治疗的97例乳腺癌患者以及54例非肿瘤（乳腺腺病）患者的手术标本，制作组织芯片，利用免疫组化染色法研究乳腺癌和正常乳腺（乳腺腺病）组织中精氨酸代琥珀酸合成酶（argininosuccinate synthase 1，ASS1）的表达情况，并确定其与临床病理特征和预后之间的关系。分析TCGA及GTEx数据库发现，尿素循环关键分子ASS1在乳腺癌中表达下降，并与患者的预后显著相关（ p < 0.05）。免疫组化染色显示ASS1主要定位于胞浆，在乳腺癌中表达下降，且与Ki-67表达及分子分型显著相关（ p ＝0.021 5，0.000 5）。ASS1在乳腺癌中表达显著下降，与肿瘤的分子分型、Ki-67表达密切相关，推测其在肿瘤发生发展中起着重要的作用。因此，ASS1低表达可以作为评估乳腺癌预后的潜在指标。 To determine the key molecule in breast cancer pathology and clinical prognosis by data analysis as well as surgical specimens immunohistochemical staining analysis. TCGA and GTEx databases were used to screen key molecules in the urea cycle with differential expression in breast, and their relationship with the prognosis of breast cancer patients was also analyzed. Then, the surgical specimens of 97 breast cancer patients and 54 non-neoplastic (mammary gland disease) patients who underwent surgical treatment in Xijing Hospital from November 2010 to December 2016 were collected to produce breast cancer tissue chips. Immunohistochemical staining was employed to determine the expression of ASS1 (argininosuccinate synthase 1) in breast cancer and adjacent normal tissues, and to verify its relationship with pathological features and prognosis of breast cancer. TCGA and GTEx database analysis showed that the expression of ASS1 decreased in breast cancer, significantly correlated with the prognosis of patients ( p < 0.05). Immunohistochemical results demonstrated that ASS1 is mainly located in cytoplasm. Its expression decreased in breast cancer, and significantly correlated with Ki-67 level and molecular typing ( p =0.021 5, p =0.000 5). The expression of ASS1 significantly decreased in breast cancer, and closely related to molecular typing and Ki-67 level, suggesting that ASS1 plays an important role in the occurrence and development of tumor. Therefore, low ASS1 expression can be used as a potential indicator to evaluate the prognosis of breast cancer. 尿素循环 ASS1(精氨酸代琥珀酸合成酶) 乳腺癌 预后 urea cycle argininosuccinate synthase 1 (ASS1) breast cancer prognosis 参考文献 SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries 刘宗超 , 李哲轩 , 张阳 , 等 . 2020全球癌症统计报告解读 [J]. 肿瘤综合治疗电子杂志 , 2021 , 7 ( 2 ): 1 - 14 . 2020全球癌症统计报告解读 LIU Z C , LI Z X , ZHANG Y , et al . Interpretation on the report of global cancer statistics 2020 [J]. Journal of Multidisciplinary Cancer Management(Electronic Version) , 2021 , 7 ( 2 ): 1 - 14 . Interpretation on the report of global cancer statistics 2020 WEI J L , JIANG Y Z , SHAO Z M . The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype [J]. The Breast , 2020 , 51 : 40 - 49 . The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype 蒋梦怡 , 陆言巧 , 王红霞 . 乳腺癌异质性的研究进展及临床意义 [J]. 中国癌症杂志 , 2020 , 30 ( 5 ): 394 - 400 . 乳腺癌异质性的研究进展及临床意义 JIANG M Y , LU Y Q , WANG H X . Research progress and clinical significance of breast cancer heterogeneity [J]. China Oncology , 2020 , 30 ( 5 ): 394 - 400 . Research progress and clinical significance of breast cancer heterogeneity KESHET R , SZLOSAREK P , CARRACEDO A , et al . Rewiring urea cycle metabolism in cancer to support anabolism [J]. Nat Rev Cancer , 2018 , 18 ( 10 ): 634 - 645 . Rewiring urea cycle metabolism in cancer to support anabolism EREZ A , NAGAMANI S C , LEE B . Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond [J]. Am J Med Genet C Semin Med Genet , 2011 , 157C ( 1 ): 45 - 53 . Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond HUSSON A , BRASSE-LAGNEL C , FAIRAND A , et al . Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle [J]. Eur J Biochem , 2003 , 270 ( 9 ): 1887 - 1899 . Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle 王冰梅 . 一氧化氮合成与尿素循环酶的关系：“瓜氨酸－一氧化氮循环” [J]. 中国体育科技 , 2005 , 41 ( 5 ): 130-131,140 . 一氧化氮合成与尿素循环酶的关系：“瓜氨酸－一氧化氮循环” WANG B M . The relation of nitric oxide synthesis and urea cycle enzymes [J]. China Sport Science and Technology , 2005 , 41 ( 5 ): 130-131,140 . The relation of nitric oxide synthesis and urea cycle enzymes MORRIS S M . Regulation of enzymes of the urea cycle and arginine metabolism [J]. Annu Rev Nutr , 2002 , 22 : 87 - 105 . Regulation of enzymes of the urea cycle and arginine metabolism HOOPER R C , HSU J , DUNCAN A , et al . Breast cancer knowledge and decisions made for contralateral prophylactic mastectomy: A survey of surgeons and women in the general population [J]. Plastic and Reconstructive Surgery , 2019 , 143 ( 5 ): 936e - 945e . Breast cancer knowledge and decisions made for contralateral prophylactic mastectomy: A survey of surgeons and women in the general population LEE J G . A meta-analysis of the association between physical activity and breast cancer mortality [J]. Cancer Nursing , 2019 , 42 ( 4 ): 271 - 285 . A meta-analysis of the association between physical activity and breast cancer mortality 林燕 , 徐颖 , 曹希 , 等 . 老年乳腺癌患者的综合治疗方式选择及其影响因素分析 [J]. 中华医学杂志 , 2022 , 102 ( 6 ): 428 - 434 . 老年乳腺癌患者的综合治疗方式选择及其影响因素分析 LIN Y , XU Y , CAO X , et al . Comprehensive treatment options and influencing factors in elderly patients with breast cancer [J]. National Medical Journal of China , 2022 , 102 ( 6 ): 428 - 434 . Comprehensive treatment options and influencing factors in elderly patients with breast cancer KOBAYASHI E , MASUDA M , NAKAYAMA R , et al . Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma [J]. Molecular Cancer Therapeutics , 2010 , 9 ( 3 ): 535 - 544 . Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma HUANG H Y , WU W R , WANG Y H , et al . ASS1 as a novel tumor suppressor gene in myxofibrosarcomas: Aberrant loss via epigenetic DNA methylation confers aggressive phenotypes, negative prognostic impact, and therapeutic relevance [J]. Clinical Cancer Research , 2013 , 19 ( 11 ): 2861 - 2872 . ASS1 as a novel tumor suppressor gene in myxofibrosarcomas: Aberrant loss via epigenetic DNA methylation confers aggressive phenotypes, negative prognostic impact, and therapeutic relevance XIONG L F , TENG J L L , BOTELHO M G , et al . Arginine metabolism in bacterial pathogenesis and cancer therapy [J]. Int J Mol Sci , 2016 , 17 ( 3 ): 363 . Arginine metabolism in bacterial pathogenesis and cancer therapy MORRIS S M . Recent advances in arginine metabolism: Roles and regulation of the arginases [J]. Br J Pharmacol , 2009 , 157 ( 6 ): 922 - 930 . Recent advances in arginine metabolism: Roles and regulation of the arginases MARION V , SANKARANARAYANAN S , THEIJE C , et al . Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice [J]. PLoS One , 2013 , 8 ( 6 ): e67021 . Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice RABINOVICH S , ADLER L , YIZHAK K , et al . Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis [J]. Nature , 2015 , 527 ( 7578 ): 379 - 383 . Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis