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EP094/#1572  Unraveling the complexities of cervical cancer: exploration of molecular mechanisms and immunological dichotomies between squamous cell carcinoma and adenocarcinoma
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  1. Morteza Salarzaei1,
  2. Ralf Van De Laar1,
  3. Patricia C Ewing-Graham1,
  4. Shiva Najjary2,
  5. Edith Van Esch3,
  6. Heleen Van Beekhuizen1 and
  7. Dana Mustafa2
  1. 1Erasmus MC Cancer institute, University Medical Center Rotterdam, Gynecologic Oncology, Rotterdam, Netherlands
  2. 2The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Department of Pathology and Clinical Bioinformatics, Rotterdam, Netherlands
  3. 3Catharina Ziekenhuis Eindhoven, Department of Gynecology and Obstetrics, Eindhoven, Netherlands

Abstract

Introduction This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring the differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways among the two predominant histological types: Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC).

Methods This study builds upon our previous research that included samples of primary cervical cancer patients.1 The samples were grouped based on their histopathology; comparing SCC to ADC. Existed targeted gene expression data were reanalyzed using the advanced analysis module of nSolver software (nanoString Technology).

Results The study included 22 cervical cancer patients, with 12 patients diagnosed with SCC and 10 with ADC. A total of 33 genes were found to be significantly differentially expressed between the two groups, 23 genes of them were overexpressed in SCC compared to ADC (Benjamini-Yekutieli (BY) adjusted p-value < 0.05). Importantly, the immune checkpoint CD274 and CTLA4 were identified as highly express in the SCC compared to ADC. In addition, the immune cell comparison revealed that B cells, T cells, and the cytotoxic cells infiltrated in higher abundancy in SCC compared to ADC. In the same lines, the pathway analysis showed higher scores of cytotoxicity, interferon signaling, metabolic stress, and Notch signaling pathways (adjusted p-value = 0.01, 0.03, 0.03, and 0.01 respectively) in SCC samples.

Conclusion/Implications Our findings elucidate distinctive gene expression patterns, signaling pathway activations, and immune cell infiltration trends in SCC compared to ADC. The findings of this study highlight that all primary cervical cancer is not the same and might be beneficial to subdivide it based on the histological and molecular differences.

Reference

  1. de Geus V, Ewing-Graham PC, de Koning W, de Koning MN, van den Bosch TP, Nigg AL, van Eijck CH, Jozwiak M, van Beekhuizen HJ, Mustafa DA. Identifying molecular changes in early cervical cancer samples of patients that developed metastasis. Frontiers in Oncology 2022 Jan 11;11:715077.

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