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GENE:

SHOX2 (SHOX Homeobox 2)

i
Other names: SHOX2, SHOX Homeobox 2, OG12X, SHOT, Short Stature Homeobox 2, OG12, SHOX Homologous Gene On Chromosome 3, Paired-Related Homeobox Protein SHOT, Short Stature Homeobox Protein 2, Homeobox Protein Og12X
Associations
1m
Downregulation of short-stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β-catenin signaling. (PubMed, Drug Dev Res)
Collectively, SHOX2 may serve as a prognostic marker for GC patients, and downregulation of SHOX2 could effectively impede GC cell growth and stemness by inactivating the wnt/β-catenin signaling pathway. These findings underscore the potential of SHOX2 as a promising therapeutic target for GC.
Preclinical • Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • SHOX2 (SHOX Homeobox 2)
2ms
Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics. (PubMed, Chin Med)
Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.
Journal
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LAG3 (Lymphocyte Activating 3) • TNFA (Tumor Necrosis Factor-Alpha) • PRDM1 (PR/SET Domain 1) • SERPINE1 (Serpin Family E Member 1) • SHOX2 (SHOX Homeobox 2)
4ms
Combined ultrasound endoscopy-guided fine-needle aspiration with DNA methylation of SHOX2 and RASSF1A genes to enhance the auxiliary diagnostic precision of pancreatic cancer. (PubMed, Heliyon)
Therefore, the methylation assay based on the combined SHOX2 and RASSF1A genes in EUS-FNA puncture fluid is more effective than using a single gene, liquid-based exfoliative cytology, or intravenous tumor markers for diagnosing PC. Combining the conventional marker CA19-9 enhances the diagnostic value, making it a promising approach to complement histology and cytology.
Journal • Epigenetic controller
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RASSF1 (Ras Association Domain Family Member 1) • CA 19-9 (Cancer antigen 19-9) • SHOX2 (SHOX Homeobox 2)
4ms
Combined detection of SHOX2 and PTGER4 methylation with serum marker CYFRA21-1 for improved diagnosis of malignant pleural mesothelioma. (PubMed, J Clin Pathol)
The combined detection of SHOX2 and PTGER4 methylation alongside serum CYFRA21-1 level significantly enhances the diagnosis of MPM. Additionally, CYFRA21-1 can serve as a prognostic indicator for MPM.
Journal
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PTGER4 (Prostaglandin E Receptor 4) • SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
4ms
DNA methylation analysis in plasma for early diagnosis in lung adenocarcinoma. (PubMed, Medicine (Baltimore))
Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.
Journal • Epigenetic controller
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
5ms
Novel Semi-Nested Real-Time PCR Assay Leveraging Extendable Blocking Probes for Improved SHOX2 Methylation Analysis in Lung Cancer. (PubMed, Biomolecules)
The use of ExBPs minimized non-target sequence amplification, crucial for reducing false positives. The novel semi-nested real-time PCR assay offers a cost-effective, highly sensitive, and specific method for detecting SHOX2 methylation, enhancing early lung cancer detection and monitoring, particularly valuable in resource-limited settings.
Journal
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SHOX2 (SHOX Homeobox 2)
5ms
Utility of SHOX2 and RASSF1A gene methylation detection on the residual cytology material from endobronchial ultrasound-guided transbronchial needle aspiration. (PubMed, Cytojournal)
The sensitivity of the comprehensive diagnosis (combining LBC, CB, and methylation detection) in distinguishing metastatic pulmonary epithelial malignancies in mediastinal and hilar lymph nodes or masses from benign lesions was higher (97.22%, 70/72) than that of morphological diagnosis alone (LBC and CB) (88.89%, 64/72; P < 0.05). SHOX2 and RASSF1A methylation detection demonstrates a high sensitivity and negative predictive value in the identification of pulmonary epithelial malignancies and holds promise as a valuable ancillary approach to enhance morphological diagnosis of EBUS-TBNA.
Journal • Endobronchial ultrasound • Cytology
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
6ms
Association of the SHOX2 and RASSF1A methylation levels with the pathological evolution of early-stage lung adenocarcinoma. (PubMed, BMC Cancer)
SHOX2 and RASSF1A combined (LungMe®) methylation is significantly correlated to age, gender, tumor size, TNM stage, pathological type, pleural invasion and STAS. The SHOX2 and RASSF1A methylation levels, tumor size and CTR values could predict the invasiveness of the tumor prior to surgery, thereby providing guidance for the surgical procedure.
Journal
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
9ms
Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation. (PubMed, BMC Cancer)
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.
Journal
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
9ms
The signature of cancer methylation markers in maternal plasma: Factors influencing the development and application of cancer liquid biopsy assay. (PubMed, Gene)
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.
Journal • Liquid biopsy • Biopsy
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CLIP4 (CAP-Gly Domain Containing Linker Protein Family Member 4) • RASSF1 (Ras Association Domain Family Member 1) • PTGER4 (Prostaglandin E Receptor 4) • SDC2 (Syndecan 2) • SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
10ms
Feasibility of Monitoring Response to Metastatic Prostate Cancer Treatment with a Methylation-Based Circulating Tumor DNA Approach. (PubMed, Cancers (Basel))
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.
Journal • Circulating tumor DNA • Metastases
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SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
10ms
Detection of the DNA methylation of seven genes contribute to the early diagnosis of lung cancer. (PubMed, J Cancer Res Clin Oncol)
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.
Journal • Epigenetic controller
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HOXA9 (Homeobox A9) • SOX17 (SRY-Box Transcription Factor 17) • RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2) • CDO1 (Cysteine Dioxygenase Type 1)
10ms
Hypermethylated SHOX2 in circulating cell-free DNA post renal cell carcinoma surgery as TNM-independent biomarker for recurrence risk. (PubMed, Am J Transl Res)
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.
Journal • IO biomarker • Surgery
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SHOX2 (SHOX Homeobox 2)
10ms
Evaluation of DNA methylation levels of SEPT9 and SHOX2 in plasma of patients with head and neck squamous cell carcinoma using droplet digital PCR. (PubMed, Oncol Rep)
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.
Journal • Epigenetic controller
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SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
10ms
Circulating Cell-Free SHOX2 DNA Methylation Is a Predictive, Prognostic, and Monitoring Biomarker in Adjuvant and Palliative Anti-PD-1-Treated Melanoma. (PubMed, Clin Chem)
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.
Journal • PD(L)-1 Biomarker • IO biomarker • Epigenetic controller
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SHOX2 (SHOX Homeobox 2)
10ms
Unveiling the hidden role of disulfidptosis in kidney renal clear cell carcinoma: a prognostic signature for personalized treatment. (PubMed, Apoptosis)
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.
Journal • IO biomarker
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BAP1 (BRCA1 Associated Protein 1) • AHNAK2 (AHNAK Nucleoprotein 2) • FOXM1 (Forkhead Box M1) • CHAC1 (ChaC Glutathione Specific Gamma-Glutamylcyclotransferase 1) • SHOX2 (SHOX Homeobox 2)
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BAP1 mutation • AHNAK2 mutation
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gefitinib
10ms
The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early lung cancer. (PubMed, Oncology)
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.
Journal • Epigenetic controller
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
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azacitidine
11ms
SEPT9, H4C6, and RASSF1A methylation in nasopharyngeal swabs: A reflection of potential minimally invasive biomarkers for early screening of nasopharyngeal cancer. (PubMed, Medicine (Baltimore))
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.
Journal
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GSTP1 (Glutathione S-transferase pi 1) • SOX2 • RASSF1 (Ras Association Domain Family Member 1) • SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
12ms
Performance of SHOX2 and RASSF1A methylation assay in supernatants and matched cell pellets for the diagnosis of malignant pleural effusion. (PubMed, Clin Chim Acta)
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.
Journal • Pleural effusion
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
1year
A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer. (PubMed, Chin J Cancer Res)
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.
Journal • Epigenetic controller
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TP53 (Tumor protein P53) • PTGER4 (Prostaglandin E Receptor 4) • SHOX2 (SHOX Homeobox 2)
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TP53 mutation
1year
Combined Methylation of SHOX2 and RASSF1A Genes in Diagnosing Malignant Pleural Effusion. (PubMed, Discov Med)
The detection of SHOX2 and RASSF1A methylation can effectively differentiate between BPE and MPE, especially in diagnosing pulmonary MPE.
Journal • Pleural effusion
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
1year
Diagnostic value of exfoliated tumor cells combined with DNA methylation in bronchoalveolar lavage fluid for lung cancer. (PubMed, Medicine (Baltimore))
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.
Journal • Epigenetic controller • Tumor cell
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
1year
SHOX2 promotes prostate cancer proliferation and metastasis through disruption of the Hippo-YAP pathway. (PubMed, iScience)
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.
Journal
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SHOX2 (SHOX Homeobox 2)
over1year
Methylated Circulating Tumor DNA in Blood as a Tool for Diagnosing Lung Cancer: A Systematic Review and Meta-Analysis. (PubMed, Cancers (Basel))
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.
Retrospective data • Review • Journal • Circulating tumor DNA
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
over1year
Quantitative analysis of a novel DNA hypermethylation panel using bronchial specimen for lung cancer diagnosis. (PubMed, Int J Cancer)
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.
Journal
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SHOX2 (SHOX Homeobox 2)
over1year
Cell-Free Methylated PTGER4 and SHOX2 Plasma DNA as a Biomarker for Therapy Monitoring and Prognosis in Advanced Stage NSCLC Patients. (PubMed, Diagnostics (Basel))
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.
Journal • Metastases
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PTGER4 (Prostaglandin E Receptor 4) • SHOX2 (SHOX Homeobox 2)
over1year
A potential immunotherapeutic and prognostic biomarker for multiple tumors including glioma: SHOX2. (PubMed, Hereditas)
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.
Journal • Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • SHOX2 (SHOX Homeobox 2)
over1year
A comprehensive diagnostic scheme of morphological combined molecular methylation under bronchoscopy. (PubMed, Front Oncol)
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.
Journal
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
over1year
PANAMA (PET for Assessment of NeoAdjuvant chemotherapy in patients with MAmmacarcinoma): A prospective study to carry out PET/CT and plasma biomarker determination (SHOX2 and SEPT 9) to evaluate the therapy response of primary breast cancer under neoadjuvant chemotherapy (GSS 2023)
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.
Clinical
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SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
over1year
Diagnostic performance of RASSF1A and SHOX2 methylation combined with EGFR mutations for differentiation between small pulmonary nodules. (PubMed, J Cancer Res Clin Oncol)
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.
Journal
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EGFR (Epidermal growth factor receptor) • RAS (Rat Sarcoma Virus) • RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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EGFR mutation • RASSF1 methylation
over1year
MiR-24-1-5p Hinders Malignant Phenotypes of Clear Cell Renal Cell Carcinoma by Targeting SHOX2. (PubMed, Biochem Genet)
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.
Journal
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SHOX2 (SHOX Homeobox 2)
almost2years
H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt/β-catenin and TGF-β pathways. (PubMed, Reprod Biol Endocrinol)
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.
Journal
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TGFB1 (Transforming Growth Factor Beta 1) • KRT19 (Keratin 19) • HOXB4 (Homeobox B4) • SHOX2 (SHOX Homeobox 2)
almost2years
DNA Methylation Analysis of the SHOX2 and RASSF1A Panel Using Cell-Free DNA in the Diagnosis of Malignant Pleural Effusion. (PubMed, J Oncol)
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.
Journal • Pleural effusion • Epigenetic controller
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation
almost2years
miR-375 Combined with SHOX2 Methylation has Higher Diagnostic Efficacy for Non-Small-Cell Lung Cancer. (PubMed, Mol Biotechnol)
miR-375 targeted SHOX2. Overall, miR-375 and SHOX2 methylation and their combined detection were expected to be biomarkers for the diagnosis of NSCLC.
Journal
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MIR375 (MicroRNA 375) • SHOX2 (SHOX Homeobox 2)
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miR-375 expression
2years
Cell-free DNA hypermethylated genes may have a limited role in cancer screening but a potential role in risk assessment of head and neck cancer. (PubMed, Oral Oncol)
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.
Journal • Epigenetic controller
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • HIC1 (HIC ZBTB Transcriptional Repressor 1) • SHOX2 (SHOX Homeobox 2)
2years
A detection panel of novel methylated DNA markers for malignant pleural effusion. (PubMed, Front Oncol)
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.
Journal • Pleural effusion
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HOXA9 (Homeobox A9) • RASSF1 (Ras Association Domain Family Member 1) • SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
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HOXA9 methylation
2years
Early Dynamics of Quantitative SEPT9 and SHOX2 Methylation in Circulating Cell-Free Plasma DNA during Prostate Biopsy for Prostate Cancer Diagnosis. (PubMed, Cancers (Basel))
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.
Journal
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SEPTIN9 (Septin 9) • SHOX2 (SHOX Homeobox 2)
2years
A novel hypoxia-driven gene signature that can predict the prognosis and drug resistance of gliomas. (PubMed, Front Genet)
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.
Journal • Gene Signature
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MGMT (6-O-methylguanine-DNA methyltransferase) • WT1 (WT1 Transcription Factor) • MMP9 (Matrix metallopeptidase 9) • HOXB2 (Homeobox B2) • HOXC6 (Homeobox C6) • MYOD1 (Myogenic Differentiation 1) • SHOX2 (SHOX Homeobox 2)
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MGMT unmethylation
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temozolomide
2years
Nine-gene signature and nomogram for predicting survival in patients with head and neck squamous cell carcinoma. (PubMed, Front Genet)
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.
Journal • Gene Signature
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CARD11 (Caspase Recruitment Domain Family Member 11) • HOXA9 (Homeobox A9) • CRYAB (Crystallin Alpha B) • SHOX2 (SHOX Homeobox 2)
over2years
The Diagnostic Potential of SHOX2 and RASSF1A DNA Methylation in Early Lung Adenocarcinoma. (PubMed, Front Oncol)
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.
Journal • Epigenetic controller
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RASSF1 (Ras Association Domain Family Member 1) • SHOX2 (SHOX Homeobox 2)
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RASSF1 methylation