Molecular analysis of cervical cancer tissues using Imaging Mass Spectrometry

Baliyan, Aastha (2026) Molecular analysis of cervical cancer tissues using Imaging Mass Spectrometry. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Aastha Baliyan (20RS025)) 20RS025.pdf - Submitted Version Restricted to Repository staff only Download (89MB)

Abstract

Cervical cancer is the fourth most common gynecological malignancy worldwide. Although most cases are caused by Human Papillomavirus (HPV), approximately (~10%) cases are HPV-independent and hence may escape detection and treatment, leading to poor prognosis. While histopathology remains the diagnostic gold standard, its subjective nature might lead to false positive and false negative outcomes, particularly in the early stages of the disease. Hence, there is a need for biomarker development to detect cervical cancer in early stages regardless of its HPV status. Mass spectrometry is a versatile tool widely used for biomarker development across various diseases. While traditionally used LC-MS-based omics identifies dysregulated analytes, it lacks spatial information of the expression profiles of these analytes within cancerous tissue. In contrast, Imaging Mass Spectrometry (IMS) is an unbiased, label-free technique that simultaneously maps the spatial distribution and relative abundance of numerous analytes while preserving tissue architecture. Additionally, IMS may be useful for efficiently mapping surgical margins within a tissue sample, a critical challenge in cancer surgery. In this study, cervical cancer biopsy samples were analyzed using histopathology, Imaging Mass Spectrometry (MALDI-IMS and DESI-IMS), and shotgun omics (proteomics, metabolomics, and lipidomics). Histopathology provided clinical correlation, while shotgun omics complemented IMS findings to generate a comprehensive molecular profile of the diseased tissue, highlighting the advantages of combining IMS and traditional omics to create a complete molecular picture. Comparative analysis of proteins across cervical cancer tissues with non-cancerous tissues suggested that Collagen alpha-1(I) (COL1A1) is significantly underexpressed in cervical cancer tissues, whereas tubulin beta-2C (TUBB2C) and Glucose-6-phosphate Isomerase (GPI) are overexpressed, even at early stages of cancer pathogenesis. DESI-IMS data analysis indicated an abnormally high abundance of hydroxylated phosphatidylcholine (PC) species (PC(OH)36:4 whereas classical omics suggested that glutathione metabolism is upregulated, indicating increased oxidative stress, in cancerous tissues.

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