bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.04.12.648495

Spatial differentiation of proteome in cervical cancer tissues using Imaging Mass Spectrometry

Abstract

Cervical cancer, which is the fourth most common gynaecological cancer across the globe, has a poorly understood molecular pathogenesis and etiology. Current methods of diagnosis are based on cytology, histology and presence of Human Papillomavirus (HPV). Shortcomings of these methods lie with poor quality of smears which is very common in Papanicolaou (pap) smears, limited sensitivity in terms of early detection, dependence on presence of HPV, etc. Due to its high sensitivity and non-targeted approach, Matrix Assisted Laser Desorption Ionization based Imaging Mass Spectrometry (MALDI-IMS) might be advantageous to understand the pathogenesis, molecular mechanism, precise identification of surgical margins and identification of novel biomarkers. Since it can also identify proteins in the extracellular matrix, it is especially beneficial for the tissue types with sparse cells and excessive extracellular matrix. Although tissue proteome profiling for cervical cancer were reported, the heterogeneous distribution of proteins across cervical cancer tissues havent been explored. In this study, we employed a non-targeted MALDI-IMS based approach to profile the spatial distribution of proteins within cervical cancer tissues. We observed overexpression of Keratin 5 and Prelamin A/C in the region of cervical cancer tissues which were categorically labelled with cancerous morphology using histopathological examination. Both these proteins have been earlier associated with progression and aggressiveness of other cancers like breast and prostate cancers. However, no such reports are available for cervical cancer. Further studies are required on a large dataset to validate and quantitate these proteins as biomarkers for early diagnosis and prognosis of cervical cancer.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Baliyan, A., Mohapatra, I., Paul, S., Safiriyu, A. A., Mondal, S. K., Mishra, D., Mandal, A. K.. 2025-04-18. Spatial differentiation of proteome in cervical cancer tissues using Imaging Mass Spectrometry. https://doi.org/10.1101/2025.04.12.648495

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

BAF complexes cooperate with lineage-restricted transcription factors to establish cell-state-specific regulatory programs

BRG1/BRM-associated factor (BAF) complexes are essential regulators of chromatin organization and cell identity. Genes encoding BAF subunits are among the most frequently mutated in human cancer. Yet, how disruption of a single subunit gives rise to distinct tumor states remains poorly understood. Atypical teratoid rhabdoid tumors (ATRTs) provide a compelling model, as they are uniformly driven by bi-allelic loss of the BAF subunit SMARCB1, yet segregate into distinct molecular subtypes. Using integrated multi-omics profiling of patient-derived ATRT organoids and primary tumor tissues, we show that transcriptional and chromatin accessibility changes upon SMARCB1 reconstitution are directed by subtype- and lineage-specific transcription factor (TF) repertoires. Genome-wide binding and transcriptomic analyses reveal that SMARCB1 reconstitution enables the lineage-specific TF RFX4 to engage regulatory elements and activate neuronal differentiation programs, partially reprogramming ATRT-MYC toward an ATRT-SHH-like identity. Together, these findings demonstrate that SMARCB1 loss disrupts TF-dependent chromatin priming, revealing that the lineage-specific regulatory output of BAF complexes is constrained by the underlying TF repertoire.

cancer biology↗

Curvature-based schedule ordering is preserved in homogeneous and heterogeneous tumors

During treatment, dosing protocols with identical total dose may favor one schedule over another depending on how exposure is distributed over time. In homogeneous cell populations, Jensen's inequality has been shown to predict whether continuous or intermittent high-dose followed by low-dose is favored, based on the curvature of the concentration-effect function. Scheduling ordering can be performed based on curvature only: concave functions favor continuous dosing while convex functions favor intermittent dosing schedules with a high time-variance. However, tumors exhibit heterogeneous drug sensitivities, and treatment preferentially eliminates drug-sensitive cells, progressively shifting the surviving population toward greater drug resistance. Whether this treatment-induced selection can reverse curvature-based schedule ordering remains unclear. We develop a mathematical framework in which phenotypes share a common concentration-effect function but differ by fixed, nonnegative sensitivity scales. We prove that the ordering of equal-mean schedules is administrated solely by the scalar cumulative treatment effect, that is, by the curvature of the effect function alone. Consequently, baseline heterogeneity and treatment-induced selection can alter the magnitude of treatment response and the composition of surviving cells, but cannot reverse the ordering of equal-mean schedules predicted by the curvature of the single-cell concentration-effect function. This preservation holds across different temporal dosing profiles and repeated treatment cycles. Our work uncovers a general principle that curvature-based schedule ordering is preserved in heterogeneous tumors despite treatment-induced selection toward resistance.

cancer biology↗

Enhanced antitumour activity of combined PD-1 blockade and HER2-targeted therapy is associated with reduced epithelial-mesenchymal transition and extracellular matrix-remodelling signatures in gastric cancer

Background The combination of PD-1 blockade, HER2-targeted therapy and chemotherapy improves outcomes in HER2-positive advanced gastric and gastro-oesophageal junction adenocarcinoma. However, chemotherapy can independently alter the tumour microenvironment, making the biological effects of PD-1 and HER2 targeting difficult to distinguish. We therefore investigated how PD-1 and HER2 blockade, alone and in combination, affect tumour growth and associated transcriptional programmes. Methods Immunodeficient NOG mice received human PBMCs by tail-vein injection. Three days later, NCI-N87 gastric cancer cells were implanted subcutaneously. Mice were randomised to vehicle, pembrolizumab, trastuzumab, or combination treatment. Tumour growth was assessed, and bulk RNA sequencing was used to identify treatment-associated changes in gene expression, pathway enrichment, and tumour, stromal, and immune cell-associated signatures. Results Combined treatment produced greater tumour growth control than either monotherapy. Trastuzumab-treated tumours showed enrichment of immune activation, epithelial-mesenchymal transition (EMT), and TGF{beta}-associated signatures, whereas pembrolizumab alone produced a limited transcriptional effect. Combination treatment was associated with reduced proliferation, EMT, and stromal-remodelling signatures, alongside increased cytotoxic immune-associated signatures. Expression of extracellular matrix-associated genes, including VCAN, SPARC, POSTN, collagen genes, and FAP, was lower in combination-treated tumours. Complement-related transcriptional pathways were also enriched. Conclusions In this chemotherapy-free model, combined PD-1 blockade and HER2-targeted therapy was associated with greater tumour growth control, enrichment of cytotoxic immune-associated transcriptional signatures, and reduced EMT and extracellular matrix remodelling signatures. These findings provide hypotheses for further mechanistic validation.

cancer biology↗