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Introduction. Esophageal squamous cell carcinoma is a dangerous oncological disease for which there are no relevant molecular-biological and biochemical markers for diagnosis, monitoring, and prognosis. Non-coding RNAs, whose aberrant expression is characteristic of many neoplasms may be promising candidate markers.Aim. To investigate the clinical significance of the expression of long non-coding RNAs (lncRNAs) SNGH18, LCAL1, IGFL2-AS1, LINC02301 and LINC01508 in esophageal squamous cell carcinoma depending on the phenotype of the tumor stroma.Materials and methods. The study included 17 patients with esophageal squamous cell carcinoma, who were examined and treated at the N.N. Blokhin National Medical Research Center of Oncology. Gene expression levels were assessed using real-time polymerase chain reaction. Immunohistochemical analysis was conducted to evaluate the expression of CD68, CD163 and inducible nitric oxide synthase. Statistical analysis of the obtained results was performed using GraphPad Prizm v. 10. Differences in lncRNA expression between tumor samples and conditionally normal tissues were assessed using the Wilcoxon test for paired samples. Correlation analysis was carried out by calculating Spearman’s correlation coefficient. Survival analysis was conducted using Kaplan–Meier survival curves. A p-value of less than 0.05 was considered statistically significant.Results. Aberrant expression of the lncRNAs LCAL1, LINC01508 and LINC02301 was observed in tumor tissue compared to conditionally normal tissue. Specifically, the expression of LCAL1 and LINC01508 was increased in tumor tissue (p = 0,001 and p = 0,007), while the expression of lncRNA LINC02301 was decreased (p = 0,004). The expression of lncRNAs SNGH18 and IGFL2-AS1 showed no significant changes. ROC-analysis indicated that examining these lncRNA expressions is not suitable for diagnosing esophageal squamous cell carcinoma. Clinical significance analysis revealed no correlation between the studied lncRNA expressions and the clinicopathological characteristics of the disease correlation analysis of the lncRNAs SNGH18, LCAL1, IGFL2-AS1, LINC02301 and LINC01508 with the phenotype of tumor stroma macrophages demonstrated that LINC01508 was significantly and positively correlated with both the total number of macrophages (r = 0.579; p = 0.017) and the number of macrophages with cytotoxic and immunosuppressive phenotypes (r = 0.567; p = 0.004 and r = 0.496; p = 0.045, accordingly). In contrast, LCAL1 expression was inversely correlated with the number of cytotoxic macrophages (r = –0.490; p = 0.037). Prognostic analysis revealed that only lncRNA IGFL2-AS1 expression was associated with favorable prognosis in esophageal squamous cell carcinoma (hazard ratio 0.374; p = 0.039).Conclusion. Long non-coding RNAs are important regulatory elements in both normal and tumor cells, offering certain advantages for the diagnosis of oncological diseases due to their high specificity and stability in both tissues and circulating body fluids. Growing evidence from scientific research highlights the potential clinical application of lncRNA expression analysis as markers for early diagnosis and as potential therapeutic targets. In this study, we conducted a retrospective investigation and determined the clinical significance of lncRNAs SNGH18, LCAL1, IGFL2-AS1, LINC02301, LINC01508 in esophageal squamous cell carcinoma, thereby expanding our understanding of the molecular changes observed in the development of this disease.
Introduction. Esophageal squamous cell carcinoma is a dangerous oncological disease for which there are no relevant molecular-biological and biochemical markers for diagnosis, monitoring, and prognosis. Non-coding RNAs, whose aberrant expression is characteristic of many neoplasms may be promising candidate markers.Aim. To investigate the clinical significance of the expression of long non-coding RNAs (lncRNAs) SNGH18, LCAL1, IGFL2-AS1, LINC02301 and LINC01508 in esophageal squamous cell carcinoma depending on the phenotype of the tumor stroma.Materials and methods. The study included 17 patients with esophageal squamous cell carcinoma, who were examined and treated at the N.N. Blokhin National Medical Research Center of Oncology. Gene expression levels were assessed using real-time polymerase chain reaction. Immunohistochemical analysis was conducted to evaluate the expression of CD68, CD163 and inducible nitric oxide synthase. Statistical analysis of the obtained results was performed using GraphPad Prizm v. 10. Differences in lncRNA expression between tumor samples and conditionally normal tissues were assessed using the Wilcoxon test for paired samples. Correlation analysis was carried out by calculating Spearman’s correlation coefficient. Survival analysis was conducted using Kaplan–Meier survival curves. A p-value of less than 0.05 was considered statistically significant.Results. Aberrant expression of the lncRNAs LCAL1, LINC01508 and LINC02301 was observed in tumor tissue compared to conditionally normal tissue. Specifically, the expression of LCAL1 and LINC01508 was increased in tumor tissue (p = 0,001 and p = 0,007), while the expression of lncRNA LINC02301 was decreased (p = 0,004). The expression of lncRNAs SNGH18 and IGFL2-AS1 showed no significant changes. ROC-analysis indicated that examining these lncRNA expressions is not suitable for diagnosing esophageal squamous cell carcinoma. Clinical significance analysis revealed no correlation between the studied lncRNA expressions and the clinicopathological characteristics of the disease correlation analysis of the lncRNAs SNGH18, LCAL1, IGFL2-AS1, LINC02301 and LINC01508 with the phenotype of tumor stroma macrophages demonstrated that LINC01508 was significantly and positively correlated with both the total number of macrophages (r = 0.579; p = 0.017) and the number of macrophages with cytotoxic and immunosuppressive phenotypes (r = 0.567; p = 0.004 and r = 0.496; p = 0.045, accordingly). In contrast, LCAL1 expression was inversely correlated with the number of cytotoxic macrophages (r = –0.490; p = 0.037). Prognostic analysis revealed that only lncRNA IGFL2-AS1 expression was associated with favorable prognosis in esophageal squamous cell carcinoma (hazard ratio 0.374; p = 0.039).Conclusion. Long non-coding RNAs are important regulatory elements in both normal and tumor cells, offering certain advantages for the diagnosis of oncological diseases due to their high specificity and stability in both tissues and circulating body fluids. Growing evidence from scientific research highlights the potential clinical application of lncRNA expression analysis as markers for early diagnosis and as potential therapeutic targets. In this study, we conducted a retrospective investigation and determined the clinical significance of lncRNAs SNGH18, LCAL1, IGFL2-AS1, LINC02301, LINC01508 in esophageal squamous cell carcinoma, thereby expanding our understanding of the molecular changes observed in the development of this disease.
Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines. Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance. Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median). Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms. Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.
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