Transcriptomic profiling of select genes associated with cervical cancer and its preneoplastic lesions in Nigerian patients: an in vivo and in silico study

Abstract

Cervical cancer remains a leading cause of cancer-related mortality among women in Nigeria, primarily due to late detection. Genetic alterations in host genes contribute significantly to its pathogenesis. This study aims to validate the differential expression, mutational status, and clinical significance of SPP1, ANXA1, ANXA3, TMEM45A, IL-18, IGHG2, KRT10, CD177, ERO1α, ANKRD31, GSTA4, and MREG genes in patients presenting with symptoms of cervical cancer. A total of twenty-four (24) consenting female patients were recruited for this study; twenty-one (21) of them were those presenting with symptoms of cervical cancer, and the remaining three (3) were those who were clinically and histologically confirmed not to have any symptoms of cervical cancer. Tissue samples were obtained surgically and examined histopathologically. Total RNA was isolated, and gene expression levels were quantified using RT-qPCR. Gene expression across normal, tumour, and metastatic tissues, and their association with cancer hallmarks, were analysed using TNMPlot, muTarget, and Cancer Hallmark Enrichment Plot. Gene ontology and functional enrichment analyses were also performed. Histopathological analysis identified eight morphological categories: normal control (NC), mild infiltration/inflammation (MI), low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), chronic cervicitis (ChC), well-differentiated squamous cell carcinoma (WISCC), moderately-differentiated squamous cell carcinoma (MSCC), and poorly-differentiated squamous cell carcinoma (PISCC). Most of the genes were upregulated in MI, LSIL, MSCC, HSIL, WISCC, and ChC, indicating roles in proliferation, immune evasion, and metastasis. Notably, ERO1α, IGHG2, IL-18, TMEM45A, GSTA4, ANXA1, and ANXA3 were downregulated in early-stage lesions, supporting their potential as early diagnostic biomarkers. The present study findings highlight the studied genes as key contributors to cervical cancer progression and underscore their potential utility as biomarkers for early detection and targeted therapy in Nigerian women.