Identification of Metabolism-Related Prognostic Biomarkers and Immune Features of Head and Neck Squamous Cell Carcinoma.

We aimed to identify an effective metabolic subtype and risk score to predict survival and immunotherapy response in head and neck squamous cell carcinoma (HNSCC). Data were obtained from an online database. We screened significant prognostic metabolism-related genes between the normal and tumor groups using a series of bioinformatics methods. Based on the selected prognostic genes, we conducted a subtype analysis to identify significantly different subtypes in HNSCC. We then investigated survival, immune features, and hallmark differences among different subtypes. LASSO was utilized to identify optimal genes for the risk score model construction. Finally, distribution of the risk score samples was analyzed for different subtypes. A total of 32 significantly prognostic metabolism-related genes were screened, and all samples were grouped into two subtypes: cluster 1 and cluster 2. Cluster 1 had worse survival. Different immune cell infiltration (CD8 T cells, macrophages, and regulatory T cells) and immune checkpoint gene expression (PD-1 and CLAT-4) were observed between the two clusters. Twelve optimal genes were involved in risk score model, and high-risk group had poorer survival. Cluster 1 contained more high-risk samples (60%). Finally, four genes CAV1, GGT6, PYGL, and HS3ST1 were identified as significantly related to immune cells, and these genes were differentially expressed in the normal oral epithelial cells and HNSCC cells. The subtypes and risk score model in the study provide a promising biomarker for prognosis and immunotherapy response.

Achievement of long-term local control after radiation and anti-PD-1 immunotherapy in locally advanced non-small cell lung cancer.

Although concurrent chemoradiotherapy (CRT) is recommended as standard of care in patients with locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC), many patients who refuse or are not eligible for chemotherapy received radiotherapy (RT) alone with 5-year overall survival (OS) rate of about 5-6%. Immune-checkpoint inhibitors have demonstrated objective antitumor responses in patients with advanced NSCLC, but it is unclear how these agents can be used in the curative therapy with concurrent radiation. We report three cases of stage III unresectable NSCLC patients who refused chemotherapy received radiation and pembrolizumab immunotherapy. All patients had no local-regional recurrence with acceptable tolerance.

Single­cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer.

Intratumoral heterogeneity, particularly the potential cancer stemness of single cancer cells, has not yet been fully elucidated in human esophageal cancer. Single­cell transcriptome sequencing of two types of esophageal adenocarcinoma (EAC) and two types of esophageal squamous cell carcinoma (ESCC) tissues was performed, and the intratumoral cancer stemness of the types of esophageal cancer were characterized at the single­cell level in the present study. By comparing the transcriptomic profiles of single cancer cells with high and low stemness in individual patients, it was revealed that the overexpression of cell cycle­associated genes in EAC cells was highly correlated with stemness, whereas overexpression of genes involved in the signaling pathways of DNA replication and DNA damage repair was significantly correlated with stemness in ESCC. High expression of these stemness­associated genes was correlated with poor prognosis of patients. Additionally, poly [ADP­ribose] polymerase(PARP)4 was identified as a novel cancer stemness­associated gene in ESCC and its association with survival was validated in a cohort of 121 patients with ESCC. These findings have profound potential implications for the use of cell cycle inhibitors in EAC and PARP inhibitors in ESCC, which may provide novel mechanistic insights into the plasticity of esophageal cancer.

20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6-12 months. It has been demonstrated that autophagy plays an important role in EGFR-TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib. We show that the induction of autophagy in response to icotinib contributes to the development of icotinib resistance. Rg3 is capable of inhibiting autophagic flux and enhancing the sensitivity of NSCLC cells to icotinib. The resistance to icotinib could also be reversed through Rg3-induced autophagy inhibition. Autophagy inhibition by Rg3 increases the therapeutic response in both icotinib-sensitive and icotinib-resistant NSCLC cells with an EGFR-activating mutation and may be an effective new treatment strategy for this disease.

Single-cell RNA sequencing reveals diverse intratumoral heterogeneities and gene signatures of two types of esophageal cancers.

Single-cell RNA sequencing and transcriptome analysis enable novel discovery and precise characterization of new cell types and states, which improves the understanding of the cellular context of tumorigenesis. Herein, we applied this powerful approach to analyze 368 single cells from three esophageal squamous cell carcinoma (ESCC) and two esophageal adenocarcinoma (EAC) tumors. Using inferred copy number variation analysis, we successfully distinguished carcinoma cells from heterogeneous cellular populations, identifying gene signatures and crucial cancer-related signaling pathways related to ESCC and EAC. In particular, we found that NOTCH signaling was exclusively activated in ESCC, but not in EAC. ESCC tumors with higher NOTCH activity were associated with significantly worse survival rates than those with lower NOTCH activity. Collectively, this study revealed that ESCC and EAC are distinct in terms of cellular transcriptome profiles, which leads to a wide range of intratumoral cellular heterogeneity. The findings suggest that different therapeutic strategies that target the differences between two types of esophageal cancers are required, guiding cancer-specific future drug development.

[Riedel thyroiditis: two cases report].

Riedel thyroiditis is a benign disease, which is often self-limited. Examinations, such as CT and histologic diagnosis can distinguish it from malignant neoplasms and hashimoto's thyroiditis. Riedel thyroiditis is an uncommon form of chronic thyroiditis in which the thyroid gland is replaced by fibrous tissue. It can be cured by surgery and medicine.