Dataset Information

Identification of POU4F1 as a novel prognostic biomarker and therapeutic target in esophageal squamous cell carcinoma.

ABSTRACT:

Background

Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of POUs has been observed in several human cancers, influencing cell proliferation, tumor invasion, and drug resistance. However, their specific role in ESCC remains unknown.

Methods

We analyzed TCGA and GEO databases to assess POUs expression in ESCC tissues. Kaplan-Meier and ROC analyses were used to evaluate the prognostic value of POUs. Gene Set Enrichment Analysis and Protein-Protein interaction network were used to explore the potential pathway. Functional assays (Cell Counting Kit-8, EdU Staining assay, and cloning formation assay) and mechanism analyses (RNA-seq, flow cytometry, and Western blot) were conducted to determine the effects of POU4F1 knockdown on ESCC cell phenotypes and signaling pathways.

Results

POU4F1 and POU6F2 were upregulated in various cancer tissues, including ESCC, compared to normal tissues. POU4F1 expression was significantly correlated with patient survival and superior to previous models (AUC = 0.776). Knockdown of POU4F1 inhibited ESCC cell proliferation and affected cell cycle, autophagy, and DNA damage pathways in ESCC cells.

Conclusion

POU4F1 is a novel and promising prognostic and therapeutic target for ESCC patients, providing insights into potential treatment strategies.

SUBMITTER: Li N

PROVIDER: S-EPMC11316379 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Identification of POU4F1 as a novel prognostic biomarker and therapeutic target in esophageal squamous cell carcinoma.

Li Nan N Chen Siying S Wang Xiao X Zhang Boqing B Zeng Boning B Sun Chao C Zheng Kai K Chen Qiuling Q Wang Shaoxiang S

Cancer cell international 20240809 1

<h4>Background</h4>Esophageal cancer is a significant global health concern, ranking seventh in incidence and sixth in mortality. It encompasses two pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, with ESCC being more prevalent globally and associated with higher mortality rates. The POU (Pit-Oct-Unc) domain family transcription factors, comprising 15 members, play important roles in embryonic development and organ formation. Aberrant expression of PO ...[more]

PMID: 39123235

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Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors and there is a lack of biomarkers for ESCC diagnosis and prognosis. Family subunits of cholinergic nicotinic receptor genes (CHRNs) are involved in smoking behavior and tumor cell proliferation. Previous researches have shown similar molecular features and pathogenic mechanisms among ESCC, head and neck squamous cell carcinoma (HNSC), and lung squamous cell carcinoma (LUSC). Using edgeR, three mutual differentially expressed genes of CHRNs were found to be significantly upregulated at the mRNA level in ESCC, LUSC, and HNSC compared to matched normal tissues. Kaplan-Meier survival analysis showed that high expression of CHRNB4 was associated with unfavorable prognosis in ESCC and HNSC. The specific expression analysis revealed that CHRNB4 is highly expressed selectively in squamous cell carcinomas compared to adenocarcinoma. Cox proportional hazards regression analysis was performed to find that just the single gene CHRNB4 has enough independent prognostic ability, with the area under curve surpassing the tumor-node-metastasis (TNM) staging-based model, the most commonly used model in clinical application in ESCC. In addition, an effective prognostic nomogram was established combining the TNM stage, gender of patients, and expression of CHRNB4 for ESCC patients, revealing an excellent prognostic ability when compared to the model of CHRNB4 alone or TNM. Gene Set Enrichment Analysis results suggested that the expression of CHRNB4 was associated with cancer-related pathways, such as the mTOR pathway. Cell Counting Kit-8, cloning formation assay, and western blot proved that CHRNB4 knockdown can inhibit the proliferation of ESCC cells via the Akt/mTOR and ERK1/2/mTOR pathways, which might facilitate the prolonged survival of patients. Furthermore, we conducted structure-based molecular docking, and potential modulators against CHRNB4 were screened from FDA approved drugs. These findings suggested that CHRNB4 specifically expressed in SCCs, and may serve as a promising biomarker for diagnosis and prognosis prediction, and it can even become a therapeutic target of ESCC patients.

Project description:ObjectiveEndothelial cell-specific molecule 1 (ESM1) has been implicated as an oncogene in several types of cancer. However, the potential role of ESM1 in esophageal carcinogenesis (ESCA)/esophageal squamous cell carcinoma (ESCC) is still unclear.MethodsThe expression, function, and survival data of ESM1 were observed using a bioinformatics approach. Subsequently, the expression level of ESM1 in surgical esophageal tumors and adjacent normal tissues was detected by qRT-PCR and immunofluorescence. We further revealed protein expression by immunohistochemistry (IHC), which is related to the prognosis of patients with ESCC using survival analysis. In vitro, knockdown of ESM1 in KYSE150 and KYSE510 cell lines, colony formation assays, wound healing assays, and Transwell assays were performed.ResultsESM1 is significantly elevated in 12 of 20 types of human cancer. ESM1 is highly expressed in tumor tissue compared with adjacent normal tissue and was identified as a hub gene in ESCA. Clinical outcome endpoints of overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) curves showed that patients whose ESM1 expression was high had a lower clinical survival rate. The ESM1 high-expression group has a certain correlation with clinical stage and grade. The IHC of ESM1 further demonstrated that the higher the expression was, the worse the N classification and pTNM stage in patients with ESCC, which had a distinctly poorer overall 5-year survival rate. Univariate analysis showed that age, N classification, pTNM stage, and ESM1 expression were all prognostic factors, although multivariate Cox regression analysis showed that only pTNM stage was an independent prognostic factor. In vitro, silencing ESM1 suppressed the proliferation, migration, and invasion of KYSE150 and KYSE510 cells.ConclusionsESM1 is a hub gene in the initiation and progression of ESCA/ESCC that promotes the proliferation, migration, and invasion of esophageal cancer cells and may be a promising therapeutic target and prognostic indicator.

Dataset Information

Identification of POU4F1 as a novel prognostic biomarker and therapeutic target in esophageal squamous cell carcinoma.

Background

Methods

Results

Conclusion

Publications

Identification of POU4F1 as a novel prognostic biomarker and therapeutic target in esophageal squamous cell carcinoma.

Similar Datasets

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