Inhibition of UFM1 expression suppresses cancer progression and is linked to the dismal prognosis and immune infiltration in oral squamous cell carcinoma.

BACKGROUND: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined. METHODS: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments. RESULTS: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination. CONCLUSION: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.

The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

The intrapleural administration with thymic peptides in malignant pleural effusion: A clusteredsystematicreview and meta-analysis.

BACKGROUND: Thymic peptides (TPs) are often used to control malignant pleural effusion (MPE). So, we performed a clustered systematic review and meta-analysis to clarify the treatment regimens of TPs for MPE, demonstrate their clinical effectiveness and safety, and reveal the indications and optimal usage for a desired effectiveness. MATERIALS AND METHODS: We collected all trials of TPs for MPE from Chinese and English databases (from inception until May 2021). After evaluating their bias risk, we pooled the data from each regimen using the meta-analysis or descriptive analysis, and summarized the evidence quality using the Grading of Recommendation Assessment, Development and Evaluation approach (GRADE). RESULTS: Thirty-four trials were clustered into TPs for MPE from lung cancer or miscellaneous tumors. The TPs combined with chemical agents were mainly used in MPE from lung cancer. All five regimens, only thymosin with oxaliplatin (L-OHP) significantly improved the complete response (CR) [2.40 (1.84 to 3.13)], quality of life [2.04 (1.20 to 3.48)], 0.5- and 1-year overall survival (OS) rate [5.75 (3.02 to 10.92) and 5.29, (1.71 to 16.36)]. It also up-regulated the T lymphocyte levels, and reduced the pleurodesis failure, disease progression and adverse events. In patients with moderate to large volume, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥ 3 months, the thymosin (300 mg/time, one time/week and lasting two to eight times) with oxaliplatin (100 mg/m2) achieved a desired response. Most results were moderate quality. CONCLUSIONS: The current evidences indicate that the TPs are important pleurodesis agents, which combination with chemical agents are mainly used in MPE from lung cancer. The thymosin with L-OHP is a main regimen, which shows a significant improvement in clinical responses, antitumor immunity, and with a reasonable security. The evidence also provides indications and optimal usage for achieving a desired effectiveness.

Analysis of the Role and Regulation Mechanism of hsa-miR-147b in Lung Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database.

Objective: This study aimed to explore the role and regulatory mechanism of hsa-miR-147b in lung squamous cell carcinoma (LUSC) through The Cancer Genome Atlas (TCGA) database. Methods: The expression and clinical value of miR-147b in LUSC were analyzed in the TCGA database. The target genes of miR-147b were screened via miRWalk 2.0 and verified in TCGA database. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyzed the differential target genes of miR-147b. Kaplan-Meier survival analysis and Cox regression were used to screen the prognosis-related target genes. Results: The expression of miR-147b in LUSC tissues increased, and was associated with poor prognosis, gender, and stage of LUSC patients. The area under the curve (AUC) of miR-147b was 0.8478 by the receiver-operating characteristic curve. There were 428 differentially expressed genes of miR-147b that played a critical role in drug transport, DNA binding, calcium signaling pathway, and Ras signaling pathway through GO and KEGG. PTGIS, SUSD4, ARC, HTR2C, SHISA9, and PLA2G4D were independent risk factors for poor prognosis in LUSC patients. LUSC patients in the high-risk group had a higher risk of death. The time-dependent AUC was 0.673. Conclusions: MiR-147b might be a potential molecular marker for poor prognosis in patients with LUSC.