Mitochondrial transporter expression patterns distinguish tumor from normal tissue and identify cancer subtypes with different survival and metabolism.
Mitochondrial transporter expression patterns distinguish tumor from normal tissue and identify cancer subtypes with different survival and metabolism.
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DOI：
10.1038/s41598-022-21411-0
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发表时间：
2022-10-11
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
线粒体内膜的转运蛋白对新陈代谢是必不可少的。我们证明，编码SLC25转运蛋白的基因表达所代表的新陈代谢可以区分人类癌症。在肾透明细胞癌、结肠腺癌、肺腺癌和乳腺浸润性癌中，肿瘤与正常组织的表达比率非常显著。对19种人类癌症类型(6825个TCGA样本)和正常组织(2322个GTEx样本)的SLC25基因表达模式进行亲和繁殖训练，以生成聚类。它们将癌症与正常组织区分开来。它们还指示癌症亚型，其存活率与癌症类型的患者总数不同。通过对肾癌、结肠癌、肺癌和乳腺癌聚集性的研究，发现亚型对的癌症具有不同的预后，并且在检测的2080种代谢酶中蛋白质编码基因的表达存在差异。我们证明SLC25表达簇有助于识别已知预后不佳的CUPS(癌症-未知-原发)的起源组织，这对大多数癌症治疗的疗效至关重要。同一群内的不同癌症类型具有相似的代谢模式，这增加了此类癌症可能对现有和新的抗癌疗法做出类似反应的可能性。
Transporters of the inner mitochondrial membrane are essential to metabolism. We demonstrate that metabolism as represented by expression of genes encoding SLC25 transporters differentiates human cancers. Tumor to normal tissue expression ratios for clear cell renal cell carcinoma, colon adenocarcinoma, lung adenocarcinoma and breast invasive carcinoma were found to be highly significant. Affinity propagation trained on SLC25 gene expression patterns from 19 human cancer types (6825 TCGA samples) and normal tissues (2322 GTEx samples) was used to generate clusters. They differentiate cancers from normal tissues. They also indicate cancer subtypes with survivals distinct from the total patient population of the cancer type. Probing the kidney, colon, lung, and breast cancer clusters, subtype pairs of cancers were identified with distinct prognoses and differing in expression of protein coding genes from among 2080 metabolic enzymes assayed. We demonstrate that SLC25 expression clusters facilitate the identification of the tissue-of-origin, essential to efficacy of most cancer therapies, of CUPs (cancer-unknown-primary) known to have poor prognoses. Different cancer types within a single cluster have similar metabolic patterns and this raises the possibility that such cancers may respond similarly to existing and new anti-cancer therapies.
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影响因子：
4.6
作者：
McLaughlin KL;Hagen JT;Coalson HS;Nelson MAM;Kew KA;Wooten AR;Fisher-Wellman KH
通讯作者：
Fisher-Wellman KH
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Cohen, Robert L.;Settleman, Jeff
通讯作者：
Settleman, Jeff
影响因子：
64.8
作者：
Possemato, Richard;Marks, Kevin M.;Shaul, Yoav D.;Pacold, Michael E.;Kim, Dohoon;Birsoy, Kivanc;Sethumadhavan, Shalini;Woo, Hin-Koon;Jang, Hyun G.;Jha, Abhishek K.;Chen, Walter W.;Barrett, Francesca G.;Stransky, Nicolas;Tsun, Zhi-Yang;Cowley, Glenn S.;Barretina, Jordi;Kalaany, Nada Y.;Hsu, Peggy P.;Ottina, Kathleen;Chan, Albert M.;Yuan, Bingbing;Garraway, Levi A.;Root, David E.;Mino-Kenudson, Mari;Brachtel, Elena F.;Driggers, Edward M.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
4.8
作者：
Fiermonte, G;Palmieri, L;Walker, JE
通讯作者：
Walker, JE