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Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC., (© 2021. The Author(s).)

Background: Increasing evidence shows that dysregulated long non-coding RNAs (lncRNAs) can serve as potential biomarkers for cancer prognosis. However, lncRNA signatures, as potential prognostic biomarkers for esophageal squamous cell carcinoma (ESCC), have been seldom reported., Methods: Based on our previous transcriptome RNA sequencing analysis from 15 paired ESCC tissues and adjacent normal tissues, we selected 10 lncRNAs with high score rank and characterized the expression of those lncRNAs, by qRT-PCR, in 138 ESCC and paired adjacent normal samples. These 138 patients were divided randomly into training (n = 77) and test (n = 59) groups. A prognostic signature of lncRNAs was identified in the training group and validated in the test group and in an independent cohort (n = 119). Multivariable Cox regression analysis evaluated the independence of the signature in overall survival (OS) and disease-free survival (DFS) prediction. GO and KEGG pathway analysis, combined with cell transwell and proliferation assays, are applied to explore the function of the three lncRNAs., Results: A novel three-lncRNA signature, comprised of RP11-366H4.1.1 (ENSG00000248370), LINC00460 (ENSG00000233532) and AC093850.2 (ENSG00000230838), was identified. The signature classified patients into high-risk and low-risk groups with different overall survival (OS) and disease-free survival (DFS). For the training group, median OS: 23.1 months vs. 39.1 months, P < 0.001; median DFS: 15.2 months vs. 33.3 months, P < 0.001. For the test group, median OS: 23 months vs. 59 months, P < 0.001; median DFS: 16.4 months vs. 50.8 months, P < 0.001. For the independent cohort, median OS: 22.4 months vs. 60.4 months, P < 0.001). The signature indicates that patients in the high-risk group show poor OS and DFS, whereas patients with a low-risk group show significantly better outcome. The independence of the signature was validated by multivariable Cox regression analysis. GO and KEGG pathway analysis for 588 protein-coding genes-associated with the three lncRNAs indicated that the three lncRNAs were involved in tumorigenesis. In vitro assays further demonstrated that the three lncRNAs promoted the migration and proliferation of ESCC cells., Conclusions: The three-lncRNA signature is a novel and potential predictor of OS and DFS for patients with ESCC.

Epiglottic laryngoplasty is technically feasible as a one-stage procedure with excellent functional results. Although the Kambic-Sedlacek-Tucker (K-S-T) technique of glottic reconstruction offers early extubation with an adequate airway, a subsequent wide neoglottis may increase the chance of aspiration and a poor voice. To better restore the laryngeal functions of closure and phonation, we made some modifications on the original K-S-T technique as follows: (1) One of the lateral margins of the epiglottis with the aryepiglottic fold is sutured to the arytenoid region of the cricoid rather than a thyroid cartilage remnant. A neo-arytenoid is formed. (2) The other lateral margin of the epiglottis with the aryepiglottic fold is sutured to the cut edge of the false and true cord instead of a thyroid ala remnant. Therefore both margins of the epiglottis with the aryepiglottic folds are lowered as much as possible to the level of the glottis. A new pseudocord is formed. (3) A cartilage cut is made at the anterior aspect of the epiglottis, leaving its laryngeal surface of mucoperichondrial intact. A new anterior commissure with a sharp angle is shaped by this maneuver. Nineteen hemilaryngectomies with modified epiglottic laryngoplasty have been performed by members of the Department of Otolaryngology of Guangxi Medical College since 1984. Results in this series are fairly good and indicate that the modified epiglottic laryngoplasty is effective in enhancing functional results in terms of respiration, deglutition, and phonation.

This paper reports the experience in the application of modified epiglottic laryngoplasty in 20 extended hemilaryngectomies for glottic carcinoma. The Kambic-Sedlacek-Tucker (K-S-T) technique using the epiglottis in glottic reconstruction can lead to early decannulation with an excellent airway, but a wide glottis formed after operation will increase the chance of aspiration and poor voice. Sphincteric function preservation of the glottis is a key point to success in partial laryngectomy. In order to prevent aspiration and to improve the quality of voice, the reconstructive technique as modified as follows: (1) Lateral margin of the epiglottis was sutured to the cricoid. (2) The superior edge of the epiglottis was lowered to reconstruct the ventricular band. (3) A cut was made at the anterior aspect of the epiglottis to reconstruct the anterior commissure. It is the experience of the authors that modified epiglottic laryngoplasty is better than the K-S-T technique for preservation of laryngeal function after extended hemilaryngectomy.

The activity of plasminogen activator (PA) in tissue extracts from nasopharyngeal carcinoma (NPC) was determined by means of the fibrin plate method. Development of PA activity was observed in 16 out of 25 cases investigated. Furthermore, using tissue extract of NPC with PA activity, characterization and identification of the activator were carried out by means of electrophoretic analysis, fibrin zymography and immunological analysis. The molecular weight of this PA was found to be 38,000 daltons. Additionally, a urokinase type of plasminogen activator was contained in the tissue extracts.