Turkish Journal of Pathology

Türk Patoloji Dergisi

Turkish Journal of Pathology

Turkish Journal of Pathology

2024, Vol 40, Num, 2     (Pages: 101-108)

lncRNA XIST Interacts with Regulatory T Cells within the Tumor Microenvironment in Chronic Hepatitis B-Associated Hepatocellular Carcinoma

Burcin PEHLIVANOGLU 1, Anil AYSAL 1, Cihan AGALAR 3, Tufan EGELI 3, Mucahit OZBILGIN 3, Tarkan UNEK 3, Ilkay Tugba UNEK 4, Ilhan OZTOP 4, Safiye AKTAS 1, Ozgul SAGOL 1

1 Department of Molecular Pathology, Graduate School of Health Sciences, Dokuz Eylul University, IZMIR, TURKEY
2 Department of Pathology, Dokuz Eylul University, Faculty of Medicine, IZMIR, TURKEY
3 Department of General Surgery, Dokuz Eylul University, Faculty of Medicine, IZMIR, TURKEY
4 Department of Medical Oncology, Dokuz Eylul University, Faculty of Medicine, IZMIR, TURKEY
5 Department of Basic Oncology, Dokuz Eylul University, Institute of Oncology, IZMIR, Turkey

DOI: 10.5146/tjpath.2023.13161
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Objective: Alterations in the expression of several long non-coding RNAs (lncRNAs) have been shown in chronic hepatitis B-associated hepatocellular carcinoma (CHB-HCC). Here, we aimed to investigate the association between the expression of inflammation-associated lncRNA X-inactive specific transcript (XIST) and the type of inflammatory cells within the tumor microenvironment.

Material and Methods: Twenty-one consecutive cirrhotic patients with CHB-HCC were included. XIST expression levels were investigated on formalin-fixed paraffin-embedded (FFPE) tumoral and peritumoral tissue samples by real-time polymerase chain reaction (RT-PCR). Immunohistochemical staining for CD3, CD4, CD8, CD25, CD163, CTLA4, and PD-1 were performed. The findings were statistically analyzed.

Results: Of the 21 cases, 11 (52.4%) had tumoral and 10 (47.6%) had peritumoral XIST expression. No significant association was found between the degree of inflammation and XIST expression. The number of intratumoral CD3, CD4, CD8 and CD20 positive cells was higher in XIST-expressing tumors, albeit without statistical significance. Tumoral and peritumoral XIST expression tended to be more common in patients with tumoral and peritumoral CD4high inflammation. The number of intratumoral CD25 positive cells was significantly higher in XIST-expressing tumors (p=0.01). Tumoral XIST expression was significantly more common in intratumoral CD25high cases (p=0.04). Peritumoral XIST expression was also more common among patients with CD25high peritumoral inflammation, albeit without statistical significance (p=0.19).

Conclusion: lncRNA XIST is expressed in CHB-HCC and its expression is significantly associated with the inflammatory tumor microenvironment, particularly with the presence and number of CD25 (+) regulatory T cells. In vitro studies are needed to explore the detailed mechanism.

Keywords : Hepatocellular carcinoma, lncRNA, Inflammation, Chronic hepatitis B, XIST, CD25, Regulatory