Circular RNAs (circRNAs) are one type of non-coding RNA. They act as important role in regulating various biological processes in the malignant progression. But we don't clearly know the specific mechanism of the majority circRNAs in papillary thyroid tumor progression. In the current study, we explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Therefore, targeting circKIF4A is very likely to be a potential method for treatment of papillary thyroid cancer in the future.

Chemotherapy regimens containing cisplatin remain the first-line treatments for patients with oral squamous cell cancer (OSCC); however, the treatment effect is often transient because of chemoresistance and recurrence. Understanding the mechanisms of chemoresistance in OSCC might provide novel targetable vulnerabilities. In the present study, we revealed that Forkhead box D1 (FOXD1) is upregulated in OSCC and predicted poor prognosis. Moreover, ectopic expression of FOXD1 promoted, while silencing of FOXD1 inhibited, the epithelial-mesenchymal transition (EMT) and chemoresistance of OSCC, both in vitro and in vivo. Mechanistically, FOXD1 binds to the promoter of long non-coding RNA Cytoskeleton Regulator RNA (CYTOR) and activates its transcription. CYTOR then acts as a competing endogenous RNA to inhibit miR-1252-5p and miR-3148, thus upregulating lipoma preferred partner (LPP) expression. Importantly, the CYTOR/LPP axis was proven to be essential for FOXD1-induced EMT and chemoresistance in OSCC. These findings reveal a novel mechanism for the chemotherapy resistance of OSCC, suggesting that FOXD1 might be a potential prognostic marker and anti-resistance therapeutic target.

To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC). A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry. A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage (P = 0.010) and PD-L1 expression (P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival (P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence (P = 0.026). The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.

Laryngeal squamous cell carcinoma (LSCC) is a common head and neck cancer. Despite recently improved management of LSCC, chemotherapy resistance of patients remains a challenge. In this study, we identified that long noncoding RNA FOXD2-AS1 regulates LSCC therapeutic resistance by augmenting LSCC stemness. LSCC chemotherapy-resistant patients showed increased FOXD2-AS1 expression compared with that in chemotherapy-sensitive patients, which predicted poor prognosis. Gain- or loss-of-function experiments showed that upregulated FOXD2-AS1 maintained cancer stemness, reducing the response to chemotherapy, while FOXD2-AS1 downregulation had the opposite effects. FOXD2-AS1 acted as a scaffold for STAT3 and PRMT5, promoting STAT3 transcriptional activity, which is essential to maintain cancer stemness and promote chemotherapeutic resistance. Interfering with FOXD2-AS1 using short hairpin RNA rescued LSCC’s chemotherapeutic sensitivity. Thus, FOXD2-AS1 promotes LSCC chemotherapeutic resistance and is an upstream activator of STAT3, making FOXD2-AS1 a potential therapeutic target to improve the chemotherapy effect in LSCC patients.

Purpose: Whether or not young patients with squamous cell carcinoma of oral cavity (OC-SCC) have a difference in prognosis remains a controversy. This study aimed to analyze the clinical characteristics and difference of survival rates between adult patients less than 40 years of age and those 40 years of age and older.Methods: A retrospective analysis was conducted using the database of patients diagnosed with OC-SCC between 1990 and 2013 in the Sun Yat-sen University Cancer Center, but patients older than 85 years, younger than 18 years, or died within 6 months of diagnosis were excluded. Patients were categorized into two groups: the young group (< 40 years of age) and the older group (≥ 40 years of age). Cox regression, survival and subgroups analyses were performed. The primary endpoints included the rates of 5-year overall survival (OS) and disease-specific survival (DSS).Results: A total of 1902 OC-SCC patients were identified. The percentage of female in the young group was significantly higher than that in the older group (40.27% vs 31.03%,p < 0.001). This study failed to find the difference in TNM classification or tumor stage between the two groups (p > 0.05). The young group was more likely to receive adjuvant radiotherapy and/or chemotherapy (42.48% vs 26.91%,p < 0.001). The 5-year OS rate (71% vs. 57%,p < 0.001) and DSS rate (72% vs 58%,p < 0.001) in patients under 40 years were significantly higher than those for the older group.Conclusion: Our findings suggested that OC-SCC in younger patients did not present at a more advanced stage. In addition, young age is an independent predictor for better survival.

There is increasing evidence that the neutrophil-to-lymphocyte ratio (NLR) is a stage-independent predictor of poor outcome in patients with cancer. The purpose of this study was to investigate the association between cancer-specific survival (CSS), overall survival (OS), and the preoperative NLR in patients with advanced laryngeal squamous cell carcinoma (LSCC) undergoing total laryngectomy (TL).All patients with a new diagnosis of advanced laryngeal cancer (stages III and IV) presenting at the Department of Head and Neck Oncology, Sun Yat-sen University Cancer Center between January 1990 and July 2010 (n = 420) were included. To evaluate the independent prognostic relevance of the NLR, univariate and multivariate Cox regression models were used. CSS and OS were estimated using the Kaplan-Meier method.Four-hundred twenty patients were enrolled in this study. Patients with an NLR ≥2.59 showed a significantly lower CSS (P = .014) and OS (P = .032) than patients with an NLR <2.59. The Cox proportional multivariate hazard model showed that a higher preoperative NLR was independently correlated with a poor CSS and OS, with hazard ratios of 1.42 (95% confidence interval [CI] 1.06-1.91, P = .018) and 1.31 (95% CI 1.00-1.71, P = .046), respectively.The NLR may be an independent prognostic marker for CSS and OS in patients with advanced LSCC undergoing TL.