High-throughput transcriptional profiling combined with angiogenesis antibody array analysis in an orbital venous malformation cohort.

Orbital venous malformations (OVMs) are the most common benign orbital vascular disorders in adults and are characterized as enlarging encapsulated vascular neoplasms. These painless lesions grow slowly and become symptomatic with proptosis or visual disturbance. However, the pathogenic mechanism and diagnostic markers of OVMs remain poorly understood. To identify potential pathways involved in OVM formation, a cDNA microarray analysis was conducted with OVM samples and normal vascular tissues. These data were deposited in the National Omics Data Encyclopedia (NODE) database (accession number: OER033009). These pathway expression data were further confirmed by reverse transcription qPCR (RT-qPCR) in an OVM cohort. To explore the diagnostic markers in OVM, an angiogenesis antibody array was analyzed. The altered factors were further validated by enzyme-linked immunosorbent assay (ELISA) in the OVM cohort. Transcriptome screening revealed upregulated autophagy and VEGF pathways and downregulated Hippo, Wnt, hedgehog and vascular smooth muscle contraction signaling pathways in OVM samples. Furthermore, plasma EGF (p < 0.001) and Leptin (p < 0.01) levels were significantly elevated in OVM patients. Here, for the first time, we revealed the transcriptional background and plasma diagnostic markers in OVM, providing a novel understanding of OVM pathogenesis and facilitating the early diagnosis of OVM.

Mohs micrographic surgery for eyelid sebaceous carcinoma: A multicenter cohort of 360 patients.

BACKGROUND: The decision to perform Mohs micrographic surgery (MMS) or wide local excision (WLE) for eyelid sebaceous carcinoma (SC) is controversial. OBJECTIVE: To compare local recurrence, metastasis, and tumor-related mortality of patients with eyelid SC who were initially treated with MMS versus with WLE. METHODS: A multicenter cohort study. Medical records were reviewed for factors associated with recurrence, metastasis, and tumor-related mortality. All eligible patients were followed up. The impact of initial surgical modality on the prognoses were determined by Cox analyses after control for all confounders. RESULTS: Of the 360 patients included in this cohort, 115 (31.9%) underwent MMS as primary resection, whereas 245 (68.1%) underwent WLE. After a median follow-up period of 60.0 months, local recurrence was observed in 18 patients (15.7%) in the MMS group and 97 patients (39.6%) in the WLE group. Metastasis occurred in 9 patients (7.8%) who underwent MMS and 38 (15.5%) who underwent WLE. In all, 6 patients in the MMS group (5.2%) and 21 in the WLE group (8.6%) died of metastatic SC. Multivariable Cox regression indicated that compared with the WLE group, the MMS group exhibited more favorable local recurrence control (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.24-0.73; P = .002) but a comparable metastasis rate (HR, 1.38; 95% CI, 0.60-3.18; P = .453) and comparable tumor-related mortality (HR, 1.70; 95% CI, 0.59-4.93; P = .329). However, this beneficial effect became nonremarkable for patients with pagetoid intraepithelial neoplasia (HR, 1.73; 95% CI, 0.37-8.21; P = .488). LIMITATIONS: Retrospective nature of the study. CONCLUSION: MMS should be proposed for eyelid SC without orbital involvement to achieve recurrence control; however, this surgical procedure did not change the long-term outcomes in terms of metastasis or tumor-related mortality. Patients with pagetoid intraepithelial neoplasia may require adjuvant measures.

Contemporary update of overall prognosis and nomogram to predict individualized survival for Chinese patients with eyelid sebaceous carcinoma.

BACKGROUND: The prognosis of Chinese patients with eyelid sebaceous carcinoma (SC) has not been updated for >3 decades. The prognostic predictors are multifactorial, and there is no validated prognostic model for eyelid SC. METHODS: This study included 238 consecutive patients with eyelid SC. All eligible patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between the nomogram and the Tumor, Node, Metastasis (TNM) staging system. FINDINGS: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rates were 88.1% and 77.9%, respectively. Orbital involvement (HR: 3.11, p = .022), the greatest tumor basal diameter (HR: 1.06, p = .003), the presence of pagetoid spread (HR: 2.90, p = .017), and having lymph node metastasis at initial diagnosis (HR: 13.66, p < .001) were independent risk factors for tumor-related death. A nomogram integrating these 4 factors was developed with a C-index of 0.887, which is significantly better than that of the TNM staging system (p = .002). The risk groups stratified by nomogram scores (p < .001 (low vs intermediate risk); p = .001 (intermediate vs high risk)) displayed better discrimination ability than TNM staging (T1 vs T2: p = .358; T2 vs T3: p = .171; T3 vs T4: p < .001) in patients at an early stage. INTERPRETATION: The prognosis of Chinese patients with eyelid SC has improved over the last 3 decades, and it is comparable to that of patients from other countries. This nomogram provides more accurate individualized estimates of survival for eyelid SC patients and may guide clinicians in their therapeutic decisions.

Dynamic chromosomal tuning of a novel GAU1 lncing driver at chr12p13.32 accelerates tumorigenesis.

Aberrant chromatin transformation dysregulates gene expression and may be an important driver of tumorigenesis. However, the functional role of chromosomal dynamics in tumorigenesis remains to be elucidated. Here, using in vitro and in vivo experiments, we reveal a novel long noncoding (lncing) driver at chr12p13.3, in which a novel lncRNA GALNT8 Antisense Upstream 1 (GAU1) is initially activated by an open chromatin status, triggering recruitment of the transcription elongation factor TCEA1 at the oncogene GALNT8 promoter and cis-activates the expression of GALNT8. Analysis of The Cancer Genome Atlas (TCGA) clinical database revealed that the GAU1/GALNT8 driver serves as an important indicative biomarker, and targeted silencing of GAU1 via the HKP-encapsulated method exhibited therapeutic efficacy in orthotopic xenografts. Our study presents a novel oncogenetic mechanism in which aberrant tuning of the chromatin state at specific chromosomal loci exposes factor-binding sites, leading to recruitment of trans-factor and activation of oncogenetic driver, thereby provide a novel alternative concept of chromatin dynamics in tumorigenesis.

Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment.

Basal cell carcinoma (BCC) is a common malignant tumor throughout the world. One of the known risk factors of BCC is intense exposure to ultraviolet radiation. More than 50% of BCCs of the eyelid initially occur on the lower lid. The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consist of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs micrographic surgery or wide surgical excision with frozen section margin control is the first consideration for treatment of periocular BCC. Eyelid reconstruction should be carefully considered as both function and esthetic outcome in patients are important after clear excision of tumors. Exenteration is considered in the case of extensive orbital invasion or high-risk aggressive tumors in order to reduce the rate of recurrence.

ANRIL lncRNA triggers efficient therapeutic efficacy by reprogramming the aberrant INK4-hub in melanoma.

Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a "domino effect-like" therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspicious INK4b-ARF-INK4a gene cluster at chromosome 9p21, aberrant INK4a and INK4b defects were simultaneously endogenously auto-corrected after targeting the suppression of abnormal ANRIL lncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrant INK4-hub.