Cristina Gómez-Martín

Discovery and analytical assessment of urinary miRNA biomarkers for cervical cancer using advanced small RNA sequencing

M Xu, MA Molina, C Gómez-Martín, MMHS Dekker, S Ghasemi, J de Rooij, … Translational Oncology 71, 102857, 2026

Cervical cancer is primarily caused by persistent infection with high-risk human papillomavirus (hrHPV), which alters host RNA expression, including regulatory microRNAs (miRNAs). Because urine is emerging as a convenient biosource for cancer detection, we evaluated the feasibility of urinary miRNAs as non-invasive biomarkers for cervical cancer. We optimized miRNA isolation from whole urine and urine…

2026

Small and Large Extracellular Vesicles in Circulation of Diffuse Large B‐Cell Lymphoma Patients Originate From Different Cell Types of the Tumor Microenvironment

F Maltoni, S Wang, MFB Steketee, CA Gómez‐Martín, EEE Drees, … Journal of extracellular vesicles 15 (4), e70259, 2026

Malignant and non‐malignant cells within the tumor microenvironment (TME) actively secrete extracellular vesicles (EVs) that may mediate intercellular communication or enter the blood stream. Circulating EVs in Diffuse Large B‐Cell Lymphoma (DLBCL) patients are a promising source of liquid biopsy biomarkers; however, whether different cellular components of the TME preferentially secrete small (S‐) and/or large…

2026

Mesenchymal colorectal cancers secrete vesicles with unique cargo that can be used for liquid biopsy based diagnostics

PJ Asif, LH Borghuis, SR van Hooff, AE Grootemaat, MAJ van Eijndhoven, … Journal of extracellular vesicles 14 (11), e70171, 2025

Tumour‐derived extracellular vesicles (TEVs) play a crucial role in cancer progression, metastasis and therapy resistance but their distinct profiles across different cancer stages and molecular subtypes remain underexplored. This study initially analysed TEVs from all CMS subtypes in colorectal cancer (CRC) cells and continued focusing on the epithelial (CMS2) and mesenchymal (CMS4) subtypes using six…

2025

Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma

C Gómez-Martín, EEE Drees, MAJ Van Eijndhoven, NJ Groenewegen, … Cell Reports Medicine 6 (10), 2025

Multiple myeloma (MM) is a plasma cell neoplasm characterized by high inter- and intra-patient clonal heterogeneity, leading to high variability in therapeutic responses. Minimally invasive biomarkers that predict response may help personalize treatment decisions. IsoSeek, a single-nucleotide resolution small RNA sequencing method can profile thousands of microRNAs (miRNAs) and their variants (isomiRs) from patient plasma-purified…

2025

Genome Divergence Based on Entropic Segmentation of DNA

PA Bernaola-Galván, P Carpena, C Gómez-Martín, JL Oliver Entropy 27 (10), 1019, 2025

The concept of a genome signature broadly refers to characteristic patterns in DNA sequences that enable the identification and comparison of species or individuals, often without requiring sequence alignment. Such signatures have applications ranging from forensic identification of individuals to cancer genomics. In comparative genomics and evolutionary biology, genome signatures typically rely on statistical properties…

2025

Strong evidence for the evolution of decreasing compositional heterogeneity in SARS-CoV-2 genomes during the pandemic

JL Oliver, P Bernaola-Galván, P Carpena, F Perfectti, C Gómez-Martín, … Scientific Reports 15 (1), 12246, 2025

The rapid evolution of SARS-CoV-2 during the pandemic was characterized by the fixation of a plethora of mutations, many of which enable the virus to evade host resistance, likely altering the virus’ genome compositional structure (i.e., the arrangement of compositional domains of varying lengths and nucleotide frequencies within the genome). To explore this hypothesis, we…

2025

An accelerating, decreasing phylogenetic trend in SARS-CoV-2 genome compositional heterogeneity during the pandemic

JL Oliver, P Bernaola-Galván, P Carpena, F Perfectti, C Gómez-Martín, … bioRxiv, 2024.12. 03.625388, 2024

The rapid evolution of SARS-CoV-2 during the pandemic, driven by a plethora of mutations, many of which enable the virus to evade host resistance, has likely altered its genome’s compositional structure (i.e. the arrangement of compositional domains of varying lengths and nucleotide frequencies within the genome). To explore this hypothesis, we summarize the evolutionary effects…

2024

Tumor-secreted extracellular vesicles counteract therapy response by triggering inflammatory mesenchymal stem cell development

C Massaro, HN Sensoy, M Mulders, C De Schrijver, C Gómez-Martín, … Clinical Cancer Research 30 (20), 4714-4728, 2024

Purpose Therapy resistance is a major clinical hurdle in bone cancer treatment and seems to be largely driven by poorly understood microenvironmental factors. Recent evidence suggests a critical role for a unique subpopulation of mesenchymal stem cells with inflammatory features (iMSC), though their origin and function remained unexplored. We demonstrate that cancer-secreted extracellular vesicles (EV)…

2024

Full-length tRNAs lacking a functional CCA tail are selectively sorted into the lumen of extracellular vesicles

C Scheepbouwer, E Aparicio-Puerta, C Gómez-Martin, … bioRxiv, 2024

Small extracellular vesicles (sEVs) are heterogenous lipid membrane particles typically less than 200 nm in size and secreted by most cell types either constitutively or upon activation signals. sEVs isolated from biofluids contain RNAs, including small non-coding RNAs (ncRNAs), that can be either encapsulated within the EV lumen or bound to the EV surface. EV-associated…

2024

Assessing the complementary information from an increased number of biologically relevant features in liquid biopsy-derived RNA-Seq data

S Giannoukakos, S D'Ambrosi, D Koppers-Lalic, C Gómez-Martín, … Heliyon 10 (6), 2024

Liquid biopsy-derived RNA sequencing (lbRNA-seq) exhibits significant promise for clinic-oriented cancer diagnostics due to its non-invasiveness and ease of repeatability. Despite substantial advancements, obstacles like technical artefacts and process standardisation impede seamless clinical integration. Alongside addressing technical aspects such as normalising fluctuating low-input material and establishing a standardised clinical workflow, the lack of result validation…

2024

HSV-1 miRNAs are post-transcriptionally edited in latently infected human ganglia

A Zubković, C Gomes, A Parchure, M Cesarec, A Ferenčić, F Rokić, … Journal of virology 97 (10), e00730-23, 2023

Viruses use miRNAs to enable efficient replication, control host defense mechanisms, and regulate latent infection. Herpes simplex virus 1 (HSV-1) expresses multiple miRNAs whose functions are largely unknown. The evolutionary conservation of many HSV-1 miRNAs in the closely related HSV-2 suggests their functional importance. miRNAs, similar to other transcripts, can undergo various post-transcriptional modifications that…

2023

NORMSEQ: a tool for evaluation, selection and visualization of RNA-Seq normalization methods

C Scheepbouwer, M Hackenberg, MAJ van Eijndhoven, A Gerber, … Nucleic acids research 51 (W1), W372-W378, 2023

RNA-sequencing has become one of the most used high-throughput approaches to gain knowledge about the expression of all different RNA subpopulations. However, technical artifacts, either introduced during library preparation and/or data analysis, can influence the detected RNA expression levels. A critical step, especially in large and low input datasets or studies, is data normalization, which…

2023

Compositional structure of the genome: a review

P Bernaola-Galván, P Carpena, C Gómez-Martín, JL Oliver Biology 12 (6), 849, 2023

Simple Summary DNA structural biology deals with the understanding of DNA and three-dimensional chromatin structure, which can determine its function in the cell. The key structural properties of the DNA fiber, such as stability, flexibility, and susceptibility to damage, largely rely on the composition of the DNA sequence. Variations in the nucleotide sequence result in…

2023

Reassessment of miRNA variant (isomiRs) composition by small RNA sequencing

C Gómez-Martín, E Aparicio-Puerta, MAJ van Eijndhoven, JM Medina, … Cell Reports Methods 3 (5), 2023

IsomiRs, sequence variants of mature microRNAs, are usually detected and quantified using high-throughput sequencing. Many examples of their biological relevance have been reported, but sequencing artifacts identified as artificial variants might bias biological inference and therefore need to be ideally avoided. We conducted a comprehensive evaluation of 10 different small RNA sequencing protocols, exploring both…

2023

ALL-tRNAseq enables robust tRNA profiling in tissue samples

C Scheepbouwer, E Aparicio-Puerta, C Gomez-Martin, H Verschueren, … Genes & development 37 (5-6), 243-257, 2023

Transfer RNAs (tRNAs) are small adaptor RNAs essential for mRNA translation. Alterations in the cellular tRNA population can directly affect mRNA decoding rates and translational efficiency during cancer development and progression. To evaluate changes in the composition of the tRNA pool, multiple sequencing approaches have been developed to overcome reverse transcription blocks caused by the…

2023

Comprehensive, integrative genomic analysis of microRNA expression profiles in different tissues of two wheat cultivars with different traits

C Gómez-Martín, H Zhou, JM Medina, E Aparicio-Puerta, M Hackenberg, … Functional & Integrative Genomics 23 (1), 15, 2023

Wheat is one of the most important food sources on Earth. MicroRNAs (miRNA) play important roles in wheat productivity. To identify wheat miRNAs, we constructed and sequenced sRNA libraries from leaves and roots of two wheat cultivars (RAC875 and Kukri) with many different traits. Given that available miRNA wheat complement in the plant-specific database PmiREN…

2023

Genome-wide analysis of microRNA expression profile in roots and leaves of three wheat cultivars under water and drought conditions

C Gómez-Martín, H Zhou, JM Medina, E Aparicio-Puerta, B Shi, … Biomolecules 13 (3), 440, 2023

Wheat is one of the most important food sources on Earth. MicroRNAs (miRNAs) play important roles in wheat productivity. To identify wheat miRNAs as well as their expression profiles under drought condition, we constructed and sequenced small RNA (sRNA) libraries from the leaves and roots of three wheat cultivars (Kukri, RAC875 and Excalibur) under water…

2023

sRNAtoolbox: Dockerized Analysis of Small RNA Sequencing Data in Model and Non-model Species

C Gómez-Martín, E Aparicio-Puerta, M Hackenberg MicroRNA Detection and Target Identification: Methods and Protocols, 179-213, 2023

The current versions of the microRNA databases MiRgeneDB, miRBase, and PmiREN contain annotations for a total of 358 different species. Public repositories, however, host small RNA sequencing data for over 800 species. This discrepancy implies that microRNA research is also very active in species that neither have an available high-quality genome assembly nor annotations for…

2023

Single-nucleotide resolution sequencing of vesicle-associated miRNAs (IsoSeek) for treatment response detection in Multiple Myeloma

EEE Drees, MAJ van Eijndhoven, C Gómez-Martín, E Aparicio-Puerta, … VU Research Portal, 131, 2023

Since the role of high-abundant, circulating RNA as liquid biopsy disease biomarker is increasingly recognized, optimized sequencing protocols for clinical implementation are required. We developed IsoSeek an unbiased small RNA sequencing method that diverges from prior protocols using 5N 5’and 3’randomized adapter ends as unique molecular identifiers (UMIs). With a synthetic reference miRNA pool and…

2023

Pre-analytical considerations for multicenter extracellular vesicle-associated miRNA biomarker studies in Diffuse Large B-cell Lymphoma

EEE Drees, S Wang, C Gómez-Martín, MAJ van Eijndhoven, S Verkuijlen, … VU Research Portal, 177, 2023

Extracellular Vesicle associated microRNAs (EV-miRNAs) can serve as minimallyinvasive therapy-response biomarkers, as shown with EDTA-plasma of patients with classic Hodgkin lymphoma. One drawback of EDTA-plasma as circulating EV source is the requirement for immediate processing (< 2 hours) of blood samples as dying cells still generate EVs ex-vivo, resulting in false positive contribution to the…

2023