SHOX2 (SHOX Homeobox 2)

Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

Our study shows that cancer and fetus/placenta exhibit similar DNA methylation patterns, and some gastrointestinal cancer and lung cancer-related methylation markers also show positives in maternal plasma. This is an important consideration in the design and application of plasma-based cancer liquid biopsy assays.

mSHOX2 and mSEPT9 exhibit dynamics on mPCA treatment. This proof-of-concept study lays the groundwork for further investigation into these markers as valuable additions to treatment response monitoring in mPCA. Further validation in larger cohorts is essential for establishing clinical utility.

Collectively, this study reveals that the methylation of 7 genes has a big significance in the diagnosis of lung cancer with high sensitivity and specificity. Also, the 7 genes present with certain significance in distinguishing the GGN type lung cancer, as well as different stages.

mSHOX2 effectively identifies high-risk RCC patients post-surgery, indicating minimal residual disease. This easy to implement biomarker has potential for guiding of adjuvant therapy decisions.

The results highlighted: i) The ability of the ddPCR‑based assay to detect very low copies of methylated molecules; ii) the significant decrease in SEPT9 and SHOX2 methylation levels in the plasma of patients with HNSCC at the first time points of follow‑up with respect to T; iii) a different trend of longitudinally DNA methylation variations in small groups of stratified patients. The absolute and precise quantification of SEPT9 and SHOX2 methylation levels in HNSCC may be useful for studies with translational potential.

Our study suggests SHOX2 ccfDNAm to be an early predictor of outcome in anti-PD-1 treated melanoma patients. SHOX2 ccfDNAm testing may aid individualized treatment decision-making.

Besides, the correlation between the DRPS score and the chemotherapy-response signature indicated the potential effect of Gefitinib for high-risk patients...The DRPS model enables improved clinical management and personalized KIRC therapy. The identified biomarkers and immune characteristics offer new mechanistic insight into disulfidptosis in KIRC.

The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes.

The diagnostic ability of dual gene combination is better than that of single gene combination, among which SEPT9 and H4C6 combination has the best diagnostic effect. In conclusion, our findings suggest that H4C6, RASSF1A, and SEPT9 methylation occur more frequently in nasopharyngeal carcinoma, and their detection in nasopharyngeal swabs may be a minimally invasive tool for diagnosis of nasopharyngeal carcinoma.

The SHOX2 and RASSF1A methylation assay using cf-DNA, the primary recommended specimen type, can excellently increase the diagnostic sensitivity of MPE. A combination of methylation assay with cytological analysis can be used for auxiliary diagnosis of PE.

The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

The detection of SHOX2 and RASSF1A methylation can effectively differentiate between BPE and MPE, especially in diagnosing pulmonary MPE.

ETCs counting in combination with SHOX2 and RASSF1A methylation assays in BALF samples has demonstrated excellent sensitivity for lung cancer diagnosis and is an effective complementary tool for clinical diagnosis of lung cancer.

Further analysis revealed that SHOX2 could potentially interfere with the Hippo-YAP signaling pathway through NPHP4 activation, facilitating the oncogenic behavior of PCa cells. These findings highlight SHOX2 as an oncogene in PCa and provide a basis for developing potential therapeutic approaches against this disease.

The risk of publication bias was not significant. Based on the findings, methylated ctDNA in blood shows potential as a rule-in tool for lung cancer diagnosis but requires further research, possibly in combination with other biomarkers.

When combined with cytology, rapid on-site evaluation (ROSE), and histology, the panel's sensitivity in lung cancer diagnosis was 90.8% and 95.8% in bronchial washing and brushing samples, respectively, and 100% in washing + brushing samples. Our findings suggest that quantitative analysis of the three-gene panel can improve the diagnosis of lung cancer using bronchoscopy.

In contrast, the combination of the methylation values for both genes shows a clear difference between responders vs. non-responders at the time of re-staging. Furthermore, blood drawing into tubes stabilizing the sample allows researchers more flexibility.

SHOX2 was overexpressed in multiple cancer types in TCGA cohort. SHOX2 knockdown inhibited glioma cell proliferation, migration and colony formation ability. Our study showed that SHOX2 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.

Therefore, methylated SHOX2 and RASSF1A genes may be promising tumor markers in lung cancer diagnosis. Methylation detection can be an excellent supplementary tool for cytological diagnosis and, combined with bronchoscopy, could form a more effective diagnostic process.

A therapy response was shown in seven patients in the course control of the PET CT. Summary in the PET/CT good and early response of the NACT could enable a subgroup definition of patients who can be offered dose -reduced chemotherapy or, if necessary, an early changeover of the therapy.

DNA methylation of RASSF1A and SHOX2 is a pair of promising biomarkers, which may be used in combination with other driver alterations, such as EGFR mutation, to support the differential diagnosis of LUADs, especially for stage I.

Cell function experiments demonstrated that overexpression of miR-24-1-5p significantly inhibited SHOX2 level and the malignant phenotypes of ccRCC cells. The above results illustrated that miR-24-1-5p/SHOX2 axis was critical for the oncogenesis and development of ccRCC, which might be helpful for us to understand the mechanism and novel therapeutic methods of ccRCC.

H3K4me3 instabilities alter the expression of oncogenes and tumor suppressor genes, inducing aberrant proliferation, and dysregulated Wnt/β-catenin, and TGF-β pathways, that ultimately promote uterine leiomyoma progression. The reversal of these histone modifications may be a promising new therapeutic alternative for uterine leiomyoma patients.

The SHOX2 and RASSF1A methylation detection of PE-cfDNA could be a potentially effective complementary tool for cytology in the process of differential diagnosis. In summary, PE-cfDNA could be used as a promising non-invasive analyte for the auxiliary diagnosis of MPE.

No abstract available

miR-375 targeted SHOX2. Overall, miR-375 and SHOX2 methylation and their combined detection were expected to be biomarkers for the diagnosis of NSCLC.

Odds ratios analysis revealed that SHOX2, SEPT, HIC1, CDKN2A, and CALML5 were significantly associated with increased risk of HNC development. Collectively, cfDNA hypermethylation biomarkers had a high specificity but accompanied by a low sensitivity for HNC detection, which might have a limited role in cancer screening but a potential role in risk assessment of HNC.

Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe and OncoMe. OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.

The early dynamics of methylated SEPT9 and SHOX2 in ccfDNA allow differentiation between PCa patients and patients without PCa and is a promising marker for tumor monitoring in the metastatic stage to determine tumor burden under systemic therapy.

Finally, the effects of hypoxia-driven genes on temozolomide (TMZ) resistance were analyzed by western blot, CCK-8 and colony formation assay...Knockdown the expression of SHOX2 significantly reduced the TMZ-resistance induced by hypoxia in glioma cells. Ultimately, we identified six novel hypoxia-driven genes for reliable prognostic prediction in gliomas and found that SHOX2 might be a potential target to overcome the TMZ resistance induced by hypoxia.

The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades. In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.

The combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis and tumor microenvironment in patients with LUAD.

Finally, candidate drugs were predicted that can be used as possible drugs to treat GBM patients. Overall, our investigation offered five hub genes (CTNNB1, ITGB1, TNC, EGFR, and SHOX2) that could be used as precise diagnostic and prognostic candidate biomarkers of GBM and might be used as personalized therapeutic targets to obstruct gliomagenesis.

DNA methylation of these five gene promoters was significantly lower in CTCs and plasma-cfDNA than in the primary tumors. Combination of DNA methylation analysis in CTC and plasma-cfDNA was associated with worse DFI of NSCLC patients. Additional studies are required to validate our findings in a large cohort of early stage NSCLC patients.

Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.

Although in liquid biopsy components methylation of these gene promoters was significantly lower than in the primary tumors, the combination of DNA methylation analysis in sized-based CTC fraction and plasma-cfDNA revealed clinical relevance. Additional studies are required to validate our findings in a large cohort of early stage NSCLC patients.

Our study indicated that mSHOX2 was satisfactory for distinguishing malignant from benign lung tissue and noninvasively detecting lung cancer.

The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.

SHOX2 promoter methylation in humoral components may be a potential biomarker for lung cancer diagnosis with relative high diagnostic specificity.

These findings provide a critical link between the SHOX2-STAT3-WASF3 signaling axis and metastasis and suggest that the targeting of this signaling node may represent a valuable alternative strategy for combating breast cancer metastasis.