cfRNAs as biomarkers in oncology – still experimental or applied tool for personalized medicine already?

Kolenda, Tomasz; Guglas, Kacper; Baranowski, Dawid; Sobocińska, Joanna; Kopczyńska, Magda; Teresiak, Anna; Bliźniak, Renata; Lamperska, Katarzyna

doi:10.1016/j.rpor.2020.07.007

Cited by 17 publications

(17 citation statements)

References 164 publications

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“…It is interesting, however, that piRNAs are abundant not just in CHO cells but also in secreted exosomes. So far, their existence in exosomes was mainly described in human, diagnostic contexts (Jain et al 2019 ; Kolenda et al 2020 ). We hope the given data might serve as a reference point for further research in the field of piRNA in CHO cells in general and their exosomes in particular.…”

Section: Discussionmentioning

confidence: 99%

Exploring the molecular content of CHO exosomes during bioprocessing

Keysberg

Hertel

Schelletter

et al. 2021

Appl Microbiol Biotechnol

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In biopharmaceutical production, Chinese hamster ovary (CHO) cells derived from Cricetulus griseus remain the most commonly used host cell for recombinant protein production, especially antibodies. Over the last decade, in-depth multi-omics characterization of these CHO cells provided data for extensive cell line engineering and corresponding increases in productivity. However, exosomes, extracellular vesicles containing proteins and nucleic acids, are barely researched at all in CHO cells. Exosomes have been proven to be a ubiquitous mediator of intercellular communication and are proposed as new biopharmaceutical format for drug delivery, indicator reflecting host cell condition and anti-apoptotic factor in spent media. Here we provide a brief overview of different separation techniques and subsequently perform a proteome and regulatory, non-coding RNA analysis of exosomes, derived from lab-scale bioreactor cultivations of a CHO-K1 cell line, to lay out reference data for further research in the field. Applying bottom-up orbitrap shotgun proteomics and next-generation small RNA sequencing, we detected 1395 proteins, 144 micro RNA (miRNA), and 914 PIWI-interacting RNA (piRNA) species differentially across the phases of a batch cultivation process. The exosomal proteome and RNA data are compared with other extracellular fractions and cell lysate, yielding several significantly exosome-enriched species. Key points • First-time comprehensive protein and miRNA characterization of CHO exosomes. • Isolation protocol and time point of bioprocess strongly affect quality of extracellular vesicles. • CHO-derived exosomes also contain numerous piRNA species of yet unknown function.

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Section: Discussionmentioning

confidence: 99%

Exploring the molecular content of CHO exosomes during bioprocessing

Keysberg

Hertel

Schelletter

et al. 2021

Appl Microbiol Biotechnol

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“…Accordingly, the identification of low invasive and simple biomarkers for these patients' prognosis assessment is crucial. Recently, an intensive search, including liquid biopsy based on circulating nucleic acids, such as DNA and RNA [38,39,44], has been carried out. It was previously indicated that lncRNAs can be found in tumor tissue (including HNSCC) and in bodily fluids [44,45].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, an intensive search, including liquid biopsy based on circulating nucleic acids, such as DNA and RNA [38,39,44], has been carried out. It was previously indicated that lncRNAs can be found in tumor tissue (including HNSCC) and in bodily fluids [44,45]. However, circulating lncRNA as potentially predictive and prognostic biomarkers in advanced or metastatic HNSCC were not reported.…”

Section: Discussionmentioning

confidence: 99%

Liquid lncRNA Biopsy for the Evaluation of Locally Advanced and Metastatic Squamous Cell Carcinomas of the Head and Neck

Łasińska

Kolenda

Guglas

et al. 2020

JPM

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Background: Long non-coding RNA (lncRNA) are RNA molecules that are more than 200 nucleotides long and have the ability to modify the activity of genes. They can be found in both healthy and cancer tissues, as well as in plasma, saliva and other bodily fluids. They can also be used as biomarkers of early detection, prognosis and chemotherapy resistance in several cancer types. Treatment of head and neck squamous cell carcinoma (HNSCC) patients with locally advanced disease is still difficult, and choice of treatment should be based on more precise and available biomarkers, such as those obtained from a liquid biopsy. For improvement of treatment efficacy, identification and clinical implementation of new biomarkers are of the utmost importance. Methods: Plasma samples drawn before (p1) and three cycles post (p2) (TPF: docetaxel, cisplatin, 5-fluorouracil/PF: cisplatin, 5-fluorouracil) chemotherapy from 53 HNSCC patients (17 with locally advanced and 36 with metastatic disease) and 14 healthy volunteers were studied. Expression levels of 90 lncRNA expression were analyzed using the qRT-PCR method, and the obtained results were compared between proper groups. Statistical analyses were carried out using Jupyter Notebooks (5.7.2), Python (ver. 3.6) and GraphPad Prism 8. Results: The study demonstrated the differences between the expressions of several lncRNA in cancer patients’ and healthy volunteers’ plasma, as well as between locally advanced and metastatic patients’ groups. A correlation between the response to systemic therapy and lncRNA expression levels was observed. Patients with a (high/low) expression of Alpha 250 and Emx2os showed statistically significant differences in progression free survival (PFS), as well as for overall survival (OS) depending on the level of Alpha 250, snaR, SNHG1. The univariate and multivariate Cox regression model showed Alpha 250 as the best prognostic factor for HNSCC patients. Conclusions: Liquid biopsies based on lncRNAs are promising diagnostic tools that can be used to differentiate between those with cancer and healthy individuals. Additionally, they can also serve as biomarkers for chemotherapy resistance. An identified, circulating lncRNA Alpha 250 seems to prove the best prognostic biomarker, associated with extended PFS and OS, and should be validated in a larger cohort in the future.

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“…It is also postulated that lncRNAs function as molecular sponges for miRNA, e.g., ZFAS1 lncRNA, which regulates miR-150-5p in HNSCC [23]. lncRNAs could probably be used as biomarkers in oncology, but the role of some of these transcripts is not fully understood [22,[24][25][26][27]. Detailed information about lncRNAs is described by us elsewhere [24,28].…”

Section: Pseudogene Functionsmentioning

confidence: 99%

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

Stasiak

Kolenda

Kozłowska-Masłoń

et al. 2021

Life

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Pseudogenes were once considered as “junk DNA”, due to loss of their functions as a result of the accumulation of mutations, such as frameshift and presence of premature stop-codons and relocation of genes to inactive heterochromatin regions of the genome. Pseudogenes are divided into two large groups, processed and unprocessed, according to their primary structure and origin. Only 10% of all pseudogenes are transcribed into RNAs and participate in the regulation of parental gene expression at both transcriptional and translational levels through senseRNA (sRNA) and antisense RNA (asRNA). In this review, about 150 pseudogenes in the different types of cancers were analyzed. Part of these pseudogenes seem to be useful in molecular diagnostics and can be detected in various types of biological material including tissue as well as biological fluids (liquid biopsy) using different detection methods. The number of pseudogenes, as well as their function in the human genome, is still unknown. However, thanks to the development of various technologies and bioinformatic tools, it was revealed so far that pseudogenes are involved in the development and progression of certain diseases, especially in cancer.

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cfRNAs as biomarkers in oncology – still experimental or applied tool for personalized medicine already?

Cited by 17 publications

References 164 publications

Exploring the molecular content of CHO exosomes during bioprocessing

Exploring the molecular content of CHO exosomes during bioprocessing

Liquid lncRNA Biopsy for the Evaluation of Locally Advanced and Metastatic Squamous Cell Carcinomas of the Head and Neck

The World of Pseudogenes: New Diagnostic and Therapeutic Targets in Cancers or Still Mystery Molecules?

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