Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma
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RESEARCH ARTICLE
Open Access
Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma Azer Farah1, Maria Kabbage2, Salsabil Atafi3, Amira Jaballah Gabteni2, Mouadh Barbirou1,4, Mouna Madhioub5, Lamine Hamzaoui5, Mousadak Azzouz Mohamed5, Hassen Touinsi6, Asma Ouakaa Kchaou7, Emna Chelbi8, Samir Boubaker3, Rahma Ben Abderrazek1*† and Balkiss Bouhaouala-Zahar1,9*†
Abstract Background: Gastric and colorectal cancers are the most common malignant tumours, leading to a significant number of cancer-related deaths worldwide. Recently, increasing evidence has demonstrated that cancer cells exhibit a differential expression of potassium channels and this can contribute to cancer progression. However, their expression and localisation at the somatic level remains uncertain. In this study, we have investigated the expression levels of KCNB1 and KCNA5 genes encoding ubiquitous Kv2.1 and Kv1.5 potassium channels in gastric and colorectal tumours. Methods: Gastric and colorectal tumoral and peritumoral tissues were collected to evaluate the expression of KCNB1 and KCNA5 mRNA by quantitative PCR. Moreover, the immunohistochemical staining profile of Kv2.1 and Kv1.5 was assessed on 40 Formalin-Fixed and Paraffin-Embedded (FFPE) gastric carcinoma tissues. Differences in gene expression between tumoral and peritumoral tissues were compared statistically with the Mann-Whitney U test. The association between the clinicopathological features of the GC patients and the expression of both Kv proteins was investigated with χ2 and Fisher’s exact tests. Results: The mRNA fold expression of KCNB1 and KCNA5 genes showed a lower mean in the tumoral tissues (0.06 ± 0.17, 0.006 ± 0.009) compared to peritumoral tissues (0.08 ± 0.16, 0.16 ± 0.48, respectively) without reaching the significance rate (p = 0.861, p = 0.152, respectively). Interestingly, Kv2.1 and Kv1.5 immunostaining was detectable and characterised by a large distribution in peritumoral and tumoral epithelial cells. More interestingly, inflammatory cells were also stained. Surprisingly, Kv2.1 and Kv1.5 staining was undoubtedly and predominantly detected in the cytoplasm compartment of tumour cells. Indeed, the expression of Kv2.1 in tumour cells revealed a significant association with the early gastric cancer clinical stage (p = 0.026). Conclusion: The data highlight, for the first time, the potential role of Kv1.5 and Kv2.1 in gastrointestinal-related cancers and suggests they may be promising prognostic markers for these tumours. Keywords: Gastric cancer, Colorectal cancer, Kv1.5, Kv2.1, Gene expression, Intracellular localisation, Cancer diagnosis
* Correspondence: [email protected]; [email protected]; [email protected] † Rahma Ben Abderrazek and Balkiss Bouhaouala Zahar contributed equally to this work. 1 Laboratory of Venoms and Therapeutic Biomolecules, LR16IPT08 Institute Pasteur Tunis, Tunis Belvédère- University of Tunis El Manar, 13 Place Pasteur, BP74, Tunis, Tunisia Full list of author information is a
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