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

Abstract

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.

Early Dynamics of Quantitative SEPT9 and SHOX2 Methylation in Circulating Cell-Free Plasma DNA during Prostate Biopsy for Prostate Cancer Diagnosis

“…Hereby, mRNA expression was significantly increased with tumor grading and tumor burden. This is in line with previous findings designating SHOX2 as an oncogene [ 24 ].…”

Utility of SHOX2 and RASSF1A gene methylation detection on the residual cytology material from endobronchial ultrasound-guided transbronchial needle aspiration

“…[ 20 ] The relative lower sensitivity of ADC impair diagnostic efficacy of the kit due to a considerate subset of ADCs may present hypomethylation within the SHOX2 gene body. [ 21 ] Notably, although one case each of PECOMA, lymphoma, and metastatic adenocarcinoma showed positive methylation results in this study, the excellent specificity (100%) of methylation detection in distinguishing pulmonary carcinomas from other benign lesions remained consistent with previous studies. [ 18 - 20 , 22 ] However, it is worth mentioning that the DNA concentration of the samples in this study was significantly lower compared to that of other types of pathological specimens reported in the previous research.…”

Prognostic Value of Long Noncoding RNA DLEU2 and Its Relationship with Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma

“…Moreover, studies have shown that CNVs play an important role in the progression of cancers, such as lung adenocarcinoma, breast cancer, and ovarian cancer. 29 , 44 , 45 …”

“…Previous studies have reported that CNVs, somatic mutations, and DNA methylation play a crucial role in genetic and epigenetic regulation, especially DNA methylation and CNVs, and correlate closely with oncogenesis and progression. [28][29][30] We searched for CNV levels, somatic mutations and DNA methylation of DLEU2 in KIRC and LIHC using the UCSC Xena website platform. The heat map (Figure 8) results showed that expression of DLEU2 correlated closely with CNVs and DNA methylation, but not with somatic mutations, in both KIRC and LIHC.…”