Dataset Information

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers.

ABSTRACT:

Background

X-inactive specific transcript (XIST), it has been found, is abnormal expression in various neoplasms. This work aims to explore its potential molecular mechanisms and prognostic roles in types of malignancies.

Methods

This research comprehensively investigated XIST transcription across cancers from Oncomine, TIMER 2.0 and GEPIA2. Correlations of XIST expression with prognosis, miRNAs, interacting protens, immune infiltrates, checkpoint markers, mutations of tumor-associated genes and promoter methylation were also analyzed by public databases. In addition, 98 BRCA samples were collected to investigate XIST expression and evaluate its clinicopathological value.

Results

In public databases, compared to normal tissues, XIST was lower in BRCA, CESC, COAD and so on, but increased in KIRC and PRAD. Databases also showed that XIST was a good indicator of prognosis in BRCA, COAD and so on, but a bad one in KIRC, KIRP and so on. From starBase, we found 29 proteins interacting with XIST, and identified 4 miRNAs which might be sponged by XIST in cancers. Furthermore, XIST was linked with immune infiltration, especially T cell CD4+, and was related to over 20 immune checkpoint markers. Moreover, several tumor-associated gene mutations and promoter methylation were negatively related to its expression. In addition, IHC showed that XIST in BRCA was obviously lower in comparison of normal tissues and was negatively related to lymph node invasion and TNM stage.

Conclusion

In summary, abnormal expression of XIST influenced prognosis, miRNAs and immune infiltration across cancers, especially BRCA.

SUBMITTER: Han W

PROVIDER: S-EPMC9535293 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers.

Han Wei W Shi Chun-Tao CT Ma Jun J Chen Hua H Shao Qi-Xiang QX Gao Xiao-Jiao XJ Zhou Ying Y Gu Jing-Feng JF Wang Hao-Nan HN

Heliyon 20220928 10

<h4>Background</h4>X-inactive specific transcript (XIST), it has been found, is abnormal expression in various neoplasms. This work aims to explore its potential molecular mechanisms and prognostic roles in types of malignancies.<h4>Methods</h4>This research comprehensively investigated XIST transcription across cancers from Oncomine, TIMER 2.0 and GEPIA2. Correlations of XIST expression with prognosis, miRNAs, interacting protens, immune infiltrates, checkpoint markers, mutations of tumor-assoc ...[more]

PMID: 36212008

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Project description:BackgroundTrophinin-associated protein (TROAP), a cytoplasmic protein, is essential for microtubule cytoskeleton assembly. Mounting evidence demonstrates the vital role of TROAP in regulating the proliferation and migration of cells, but it is unclear how it contributes to cancer progression.MethodsThe online portals of GEPIA2, Cancer Cell Line Encyclopedia, UALCAN, Human Protein Atlas, and PrognoScan were used to analyze TROAP expression in various tumors and further evaluate its correlation with prognosis. With Western blot and quantitative real-time PCR analysis, we validated TROAP expression levels in hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Ten pairs of HCC and CRC tissues were selected for immunohistochemistry to determine TROAP expression levels in tumors and adjacent tissues, respectively. TROAP knockdown in CRC and HCC cells to verify its role in malignant phenotypes. The genomic and post-transcriptional alterations of TROAP in tumors were determined using the cBioPortal and SangerBox databases. Also, TISIDB was used to investigate the relationship between TROAP expression and tumor microenvironment(TME) among different cancer types. Moreover, a correlation was found between the expression of TROAP and drug sensitivity using GSCALite and CellMiner databases.ResultsTROAP expression was significantly upregulated in most cancer types, which is consistent with our validated experimental results in HCC and CRC cells, and immunohistochemistry results. And a poor prognosis was linked to TROAP aberrant expression. Our findings indicated that malignant phenotypes and tumorigenesis induced by TROAP could be due to an activation of the PI3K/Akt/GSK-3β signaling pathway. Furthermore, we found a correlation between TROAP expression and genomic and post-transcriptional alterations in various tumors, including tumor mutation burden, and microsatellite instability. Next, we demonstrated that TROAP expression was associated with the infiltration of immune cells, such as neutrophils and macrophages, and correlated with immunomodulation-related genes in the TME. Additionally, the potential role of TROAP expression in predicting the sensitivity of drugs, including melphalan and chlorambucil, was demonstrated.ConclusionsCollectively, these findings indicated a significant correlation between TROAP expression and malignant phenotype, functional mechanism, survival possibility, TME, therapeutic potential, and prediction of drug sensitivity in various cancers. Hence, TROAP is a promising biomarker and therapeutic target for predicting cancer outcomes.

Dataset Information

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers.

Background

Methods

Results

Conclusion

Publications

Pan-cancer analysis of LncRNA XIST and its potential mechanisms in human cancers.

Similar Datasets

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