Sphingosine Kinase 1 is Associated With Immune Cell-Related Gene Expressions in Human Breast Cancer.
Sphingosine Kinase 1 is Associated With Immune Cell-Related Gene Expressions in Human Breast Cancer.
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DOI：
10.1016/j.jss.2020.06.057
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Wakai T
中科院分区：
文献类型：
--
作者：
Tsuchida J;Nagahashi M;Nakajima M;Katsuta E;Rashid OM;Qi Q;Yan L;Okuda S;Takabe K;Wakai T
虽然先前的实验已经暗示鞘氨醇-1-磷酸（S1 P）是免疫反应和癌症进展之间的联系，但这种相互作用的确切机制尚未在临床人体样本中进行全面研究。本研究旨在评估S1 P调节鞘氨醇激酶1（SPHK 1），S1 P产生酶，在临床人类乳腺癌手术标本的免疫/免疫反应性。通过质谱法检测肿瘤、肿瘤周围和正常人乳腺样品中的S1 P水平。使用The Cancer Genome Atlas队列的Genomics Data Commons数据门户来评估S1 P相关和免疫相关基因的表达。与肿瘤周围（P < 0.05）或正常人乳腺样品（P < 0.001）相比，肿瘤样品中的S1 P水平显著更高。SPHK 1基因在乳腺癌组织中的表达明显高于正常乳腺组织（P < 0.01）。此外，SPHK 1在乳腺癌组织中的高表达与HER 2阴性乳腺癌中不同类型的免疫相关基因如CD 68、CD 163、CD 4和FOXP 3（forkhead box P3）的表达增加相关。网络分析表明SPHK 1在S1 P信号传导和免疫细胞相关蛋白表达的相互作用中起着核心作用。我们证明，在乳腺癌患者中，S1 P主要由肿瘤组织而不是肿瘤周围组织产生。我们的数据揭示了S1 P信号转导参与免疫相关基因的调节，表明S1 P与乳腺癌患者复杂的免疫-癌症相互作用之间存在联系。
Although previous experiments have implicated sphingosine-1-phosphate (S1P) as a links between immune reactions and cancer progression, the exact mechanism of this interaction has not comprehensively studied in clinical human samples. This study sought to evaluate the S1P regulation by sphingosine kinase 1 (SPHK1), an S1P-producing enzyme, in the immunity/immuno-reactivity of clinical human breast cancer surgical specimens. S1P levels were examined in tumor, peri-tumoral and normal human breast samples by mass spectrometry. Genomics Data Commons data portal of The Cancer Genome Atlas cohort was used to assess the expression of S1P-related and immune-related genes. S1P levels were significantly higher in tumor samples compared to peri-tumoral (P < 0.05) or normal human breast samples (P < 0.001). SPHK1 gene expression was elevated in tumoral samples compared to normal breast samples (P < 0.01). Furthermore, the elevated expression of SPHK1 in breast cancer tissue was associated with an increased expression of the different kinds of immune-related genes, such as CD68, CD163, CD4, and FOXP3 (forkhead box P3), in HER2-negative breast cancer. Network analysis showed the central role of SPHK1 in the interaction of S1P signaling and expression of immune cell-related proteins. We demonstrated that S1P is mainly produced by tumor tissue, rather than peri-tumoral tissue, in breast cancer patients. Our data revealed the involvement of S1P signaling in the regulation of immune-related genes, suggesting the links between S1P and complicated immune-cancer interactions in breast cancer patients.
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1-磷酸盐的出口和功能。
DOI：
10.1016/j.bbalip.2009.02.011
发表时间：
2009-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kim RH;Takabe K;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
2.5
作者：
Nagahashi M;Yamada A;Miyazaki H;Allegood JC;Tsuchida J;Aoyagi T;Huang WC;Terracina KP;Adams BJ;Rashid OM;Milstien S;Wakai T;Spiegel S;Takabe K
通讯作者：
Takabe K
影响因子：
50.3
作者：
Jain RK
通讯作者：
Jain RK
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S