Diagnostic value of SHOX2 DNA methylation in lung cancer: a meta-analysis

Zhao, Qingtao; Guo, Tao; Wang, Huien; Zhang, Xiao-Peng; Zhang, Hua; Wang, Zhikang; Zheng, Yuxin; Duan, Guochen

doi:10.2147/ott.s94300

Cited by 18 publications

(5 citation statements)

References 36 publications

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“…However, in recent decades, many researchers have found that SHOX2 also plays an important role in multiple cancers, including lung cancer ( Schneider et al, 2011 ; Hong et al, 2014 ; Sun et al, 2019 ). Interestingly, methylation detection of SHOX2 in sputum, blood, alveolar lavage fluid, and tissue of patients has been used to screen early lung cancer patients ( Zhao et al, 2015 ; Weiss et al, 2017 ; Zhang et al, 2017 ; Shi et al, 2020 ). It is worth noting that there is little research on the potential prognostic influence and molecular mechanism of SHOX2 in lung cancer, especially in non-small-cell lung cancer (NSCLC) [mainly lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC)].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma

Zeng

Tai

et al. 2021

Front. Mol. Biosci.

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Background: Detection of SHOX2 methylation has been used to assist in the early diagnosis of lung cancer in many hospitals as SHOX2 may be important in the tumorigenesis of lung cancer. However, there are few studies on the mRNA expression, methylation, and molecular mechanism of SHOX2 in lung cancer. We aimed to explore the role of SHOX2 in lung adenocarcinoma (LUAD).Methods: First, we examined the differential expression of SHOX2 mRNA and methylation in cancerous and normal tissues using databases. Second, we analyzed the relationship between SHOX2 expression and common clinical parameters in LUAD patients. Third, we further explored the methylated level and its specific location of SHOX2 and the mainly factors of SHOX2 gene expression. Finally, we screened the correlatively expressed genes to analyze the pathways from the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes using DAVID.Results: We found that the mRNA expression of SHOX2 was higher in multiple cancers, including LUAD and lung squamous cell carcinoma (LUSC), than in normal tissues. Among LUAD patients, SHOX2 expression was higher in patients of middle–young age, with smoking history, in advanced stages, and with nodal distant metastasis. In addition, our results showed that patients with high expression of SHOX2 are prone to recurrence, poor differentiation, and poor prognosis. Thus, we identified that SHOX2 might be an oncogene for LUAD progression. The main factor influencing the high expression of SHOX2 mRNA may be DNA methylation, followed by copy number variation (CNV), but not by gene mutations in LUAD. Unexpectedly, we found that SHOX2 undergoes hypomethylation in the gene body instead of hypermethylation in the promoter. Additionally, SHOX2 has cross talk in the PI3K–Akt signaling pathway and ECM–receptor interaction.Conclusion:SHOX2 is highly expressed in most cancers. SHOX2 gene expression might be mainly regulated by methylation of its gene body in LUAD, and its high expression or hypomethylation indicates poor differentiation and poor prognosis. SHOX2 could be involved in PI3K–Akt and other important cancer-related signaling pathways to promote tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma

Zeng

Tai

et al. 2021

Front. Mol. Biosci.

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“…Among the six genes analyzed, SHOX2 exhibited the highest AUC and was the gene that better predicted malignancy among negative EBUS-TBNA samples. Methylated SHOX2 has been studied previously for detecting LC in lymph node samples obtained by EBUS-TBNA [24], in bronchial aspirates, pleural effusion, plasma, and tumor tissue [34]. A meta-analysis exploring SHOX2 methylation for LC diagnosis in different samples estimated a pooled sensitivity of 70% with 96% specificity (AUC = 0.96), supporting its value for confirming benignity for negative results [34].…”

Section: Discussionmentioning

confidence: 88%

Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

Leiro-Fernández

Chiara

Rodríguez-Girondo

et al. 2019

Cancers

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The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging.

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“…CYP19A1 , a member of the cytochrome P450 family, was previously found to be highly expressed in GC and associated with an adverse prognosis; the silencing of its expression could be useful for GC treatment 31 , 32 . A previous study showed that SHOX2 methylation represent a potential biomarker for some cancers 33 – 37 . This gene was also shown to be related to unfavorable distant metastasis-free survival and could promote WASF3 transcriptional activity to induce the growth and metastasis of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

Sun,

Kong,

et al. 2024

Sci Rep

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Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

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Diagnostic value of SHOX2 DNA methylation in lung cancer: a meta-analysis

Cited by 18 publications

References 36 publications

Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma

Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma

Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

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