Guillon Clémence, Pichereaux Carole, Lazar Ikrame, Chaoui Karima, Mouton-Barbosa Emmanuelle, Liauzun Mehdi, Gourbeyre Edith, Altiner Pinar, Bouyssié David, Stella Alexandre, Burlet-Schiltz Odile, Plaza Serge, Martineau Yvan, Fabre Bertrand
Laboratoire de Recherche en Sciences Végétales (LRSV), CNRS/UT3/INPT, 31320 Auzeville-Tolosane, France.
Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, UPS, Université de Toulouse, 31077 Toulouse, France.
Cells. 2024 Nov 28;13(23):1966. doi: 10.3390/cells13231966.
The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins. Indeed, late detection of this disease, notably due to the lack of reliable biomarkers of early-stage PDAC, and the fact that tumors rapidly develop resistance to most of the treatments used in the clinics warrant the exploration of new repertoires of molecules. In the present article, we aim to investigate the alternative proteome of pancreatic cancer cell lines as a first attempt to decipher the expression of AltProts in PDAC. Thanks to a combined data-dependent and data-independent acquisition mass spectrometry workflow, we were able to identify tryptic peptides matching 113 AltProts in a panel of 6 cell lines. In addition, we identified AltProts differentially expressed between pancreatic cancer cell lines and other cells (HeLa and HEK293T). Finally, mining the TCGA and Gtex databases showed that the corresponding transcripts encoding several AltProts we identified are differentially expressed between PDAC tumors and normal tissues and are correlated with the patient's survival.
小蛋白以及由未注释开放阅读框产生的蛋白（称为替代蛋白或AltProts）的鉴定改变了我们对蛋白质组的认识，并吸引了科学界越来越多的关注。尽管有几项研究调查了疾病中的特定AltProts，并证明了它们在这种情况下的重要性，但在许多病理学中，我们仍然缺乏关于它们的表达和功能的数据。其中，胰腺导管腺癌（PDAC）是研究替代蛋白的一个特别相关的案例。事实上，这种疾病的检测较晚，特别是由于缺乏早期PDAC的可靠生物标志物，以及肿瘤对临床上使用的大多数治疗方法迅速产生耐药性，这就需要探索新的分子库。在本文中，我们旨在研究胰腺癌细胞系的替代蛋白质组，作为破译PDAC中AltProts表达的首次尝试。借助于数据依赖和数据独立采集相结合的质谱工作流程，我们能够在一组6种细胞系中鉴定出与113种AltProts匹配的胰蛋白酶肽段。此外，我们还鉴定了胰腺癌细胞系与其他细胞（HeLa和HEK293T）之间差异表达的AltProts。最后，挖掘TCGA和Gtex数据库表明，我们鉴定出的几种AltProts的相应转录本在PDAC肿瘤和正常组织之间存在差异表达，并且与患者的生存相关。
