A circadian clock gene-related signature for predicting prognosis and its association with sorafenib response in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered diseases, including cancer. However, the role of circadian rhythm in the overall survival (OS) of patients with HCC remains unclear. Methods: We investigated the expression, copy number variation (CNV), and mutation profiles of core circadian clock genes in normal and tumor tissues. We developed and validated a messenger RNA signature (mRNASig) based on prognostic circadian clock genes. A set of bioinformatic tools were applied for functional annotation and tumor-associated microenvironment (TME) analysis. Results: Core circadian clock genes were disrupted in terms of the transcription and CNV of HCC samples. The mRNASig, including NPAS2, NR1D1, PER1, RORC, and TIMELESS, was constructed. We divided patients with HCC into high-risk group and low-risk group based on the median value of the risk score. The high-risk group had a poorer prognosis than the low-risk group. The high-risk group was associated with malignant processes (e.g., proliferation, oncogenic pathway, DNA repair), metabolism, and tumor mutational burden (TMB). Surprisingly, the low-risk group was associated with enriched angiogenesis and was linked to enhanced response to sorafenib. Moreover, the high-risk group showed poor infiltration of CD8 T cells and natural killer cells accompanied by higher expression of CTLA4, PDCD1, TIGIT, and TIM3. Additionally, the mRNASig was associated with TMB. Conclusions: The mRNASig based on core circadian clock genes is a potential prognostic signature and therapeutic strategy and is significantly associated with the malignant biology of HCC.

UBE2C mediated radiotherapy resistance of head and neck squamous cell carcinoma by regulating oxidative-stress-relative apoptosis.

PURPOSE: Radiotherapy resistance is the main obstacle in the effective treatment of advanced head and neck squamous cell carcinoma (HNSCC). Increasing scientific opinions present that ubiquitin-conjugating enzyme E2C (UBE2C) might be a target gene acting as an oncogene. METHOD: TCGA database was used to analyze the expression of UBE2C in HNSCC patients, and the relationship between UBE2C expression and prognosis. Western blot and RT-PCR were used to assess UBE2C expression before and after radiation. Then, cell viability experiment and colony formation were used to evaluate proliferation after 2 Gy radiation. Cell viability experiment, migration, and invasion were evaluated in the condition of UBE2C knock-down. Western blot and RT-PCR were used to assess the expression of apoptosis and ROS relative gene expression. Then, the xenograft model was used to evaluate the efficacy of radiation combined with UBE2C suppression. RESULT: The expression of UBE2C was high in tumors of patients with HNSCC and relatives with poor prognoses. Si-UBE2C cells showed proliferation inhibited and apoptosis enhanced after radiation. Furthermore, the mechanism of UBE2C in HNSCC radioresistance was explored. We performed RT-PCR to find the 4-HNE, which increases oxidative-stress-relative apoptosis in Si-UBE2C cells after radiation. CONCLUSIONS: Through the RT-PCR, WB, cell viability experiment, migration, invasion, and in vivo experiment, UBE2C was confirmed to downregulate oxidative-stress-relative apoptosis induced by radiation and promote the development of malignant tumor cells.

Efficacy comparison between primary total laryngectomy and nonsurgical organ-preservation strategies in treatment of advanced stage laryngeal cancer: A meta-analysis.

BACKGROUND: We aimed to provide a pooled analysis of controlled trials comparing long-term survival after primary laryngectomy and primary organ preservation methods in patients with T3-4 laryngeal cancer. METHODS: We performed random-effects meta-analyses on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and locoregional control (LRC). RESULTS: Fifteen studies met the selection criteria including 6288 patients (2696 patients who underwent primary laryngectomy and 3592 patients who underwent primary nonsurgical organ preservation therapy). There was a significant difference between the groups with respect to OS (HR 0.71, 95% CI 0.57-0.89, P = .003). However, a subgroup analysis found OS was not significantly worse for patients with T3 laryngeal cancer who received primary organ preservation compared with patients who underwent primary laryngectomy (HR 0.96, 95% CI 0.45-2.03, P = .91). There was no significant difference for DFS (HR 0.63, 95% CI 0.39-1.04, P = .07) in two groups. Patients with laryngeal cancer who underwent primary laryngectomy had a better DSS (HR 0.47, 95% CI 0.25-0.88, P = .02) and LRC (HR 0.56, 95% CI 0.390.80, P = .001) than patients who underwent primary nonsurgical organ preservation therapy. CONCLUSION: Our results support total laryngectomy for patients with T4 laryngeal cancer and show that primary organ preservation for laryngeal cancer has no advantage and also did not decrease the rate of OS in patients with T3 laryngeal cancer when compared with primary total laryngectomy.