Chaunavel, A. | bioRxiv Science

bioRxiv2024

New proteomic signature in circulating extracellular vesicles from tumor-draining vein of lung adenocarcinomas patients

Identification of noninvasive prognostic biomarkers, allowing monitoring of frequently developed relapse in patients with locally advanced non-small cell lung cancer (NSCLC), still of primary importance. Tumor-draining vein (TDV) plasma samples, are known to be enriched in circulating cancer biomarkers compared to samples from peripheral vein (PV). Thus, we thought to investigate the proteomic profile of extracellular vesicles (EVs) from TDV compared to those from PV plasma samples of patients operated for NSCLC. Purified EVs from TDV and PV plasma samples were characterized for their size distribution and concentration using nanoparticles tracking analysis (NTA). Proteomic profiling of TDV-derived EVs and PV-derived EVs were further done using mass spectrometry (nanoLC-MS/MS) analysis. In parallel, proteomic profile of tumoral and non-tumoral adjacent counterpart tissues from patients with NSCLC were investigated. Twenty patients with NSCLC, treated by surgery with curative intent, were enrolled in this study. We showed that EVs from TDV plasma samples were significantly smaller than those from PV plasma samples. Interestingly, the concentration of TDV-derived EVs were significantly higher than PV-derived EVs. However, EVs concentration and size were not associated with tumor size or other clinical characteristics. Proteomic profiling showed that 9 of the 10 most overexpressed proteins in EVs from TDV samples compared to those from PV, were associated with lung cancer diagnosis and prognosis. Remarkably, 1 protein (SRPRB) was commonly upregulated in lung tumor tissues (as compared to non-tumoral counterparts) and in TDV-derived EVs (as compared to PV-derived EVs). In contrast, 12 proteins were found to be upregulated in TDV-derived EVs and downregulated in tumor tissues. In conclusion, all of these identified proteins, carried by EVs from TDV plasma samples, might represent promising novel biomarkers for NSCLC prognosis and predicting recurrences at early stages.

cancer biology↗

bioRxiv2022

PAMR1 negatively impacts cell proliferation and migration of Human Colon Cancer HT29 Cell Line

Colorectal cancer (CRC) is becoming one of the most prevalent cancers worldwide. Among cancers, it ranks the third place in terms of incidence and the second in terms of mortality. Even though immunological test allows fast and easy diagnostic method, there is no specific and reliable methods for early detection of CRC. Despite different treatments, high risk of re-occurrence is associated with advanced and metastatic CRC stages. An exhaustive knowledge on specific biomarkers or molecular actors involved in CRC could help to eradicate tumors or limit cancer recurrence. In this study, we focused on PAMR1 (Peptidase Domain Containing Associated with Muscle Regeneration 1), which is already considered as a tumor suppressor in breast and cervical cancers. In silico analysis of RNASeq data showed that PAMR1 was significantly downregulated in CRC tissues compared to their adjacent normal ones, as well as in cervical cancer. Our analysis showed that this downregulation, probably due to promoter hypermethylation, such as in breast cancer tissues, appeared in the four cancer stages as early as the first stage. In consistency with in silico analyses, the expression of PAMR1 was found to be lower at the transcript and protein levels in CRC tissue samples compared to normal ones, as well as in different CRC cell lines (HCT116, HT29, and SW620) compared to normal colon cell line (CCD841CoN). To understand the role of PAMR1 in CRC cancer, recombinant purified PAMR1 or concentrated secretome from CHO overexpressing PAMR1 were used to exogenously treat CRC cell lines with a focus on HT-29 cells as well as Hela cervical cancer cell line known to be sensitive to PAMR1. Transient or stable transfections were also performed to determine the impact of PAMR1 overexpression in HT29 and/or HeLa cells. In this study, we finally showed that presence of PAMR1 could reduce both cell proliferation and cell migration with a positive correlation between these biological effects and PAMR1s quantity. This implies that PAMR1 expresses anti-proliferative and anti-migrative effects in CRC. Further studies to be done in order to confirm the tumor suppressive role of PAMR1 in CRC.

cancer biology↗