Long-term outcomes of endoscopic resection for well-differentiated nonampullary duodenal neuroendocrine tumors.

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

Decreased expression of hsa_circ_0112879 in oral squamous cell carcinoma and its clinicopathological implications.

Background: To identify differently expressed circular RNA (circRNA) in oral squamous cell carcinoma (OSCC) and adjacent normal tissue, construct a hsa_circ_0112879-related microRNAs (miRNAs) prognostic model, and discuss the circRNA as a biomarker for early diagnosis of OSCC. Methods: The expression of hsa_circ_0112879 in OSCC cell lines and tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was plotted to estimate its clinical significance. The potential miRNA and messenger RNA (mRNA) binding to hsa_circ_009755 were predicted by R software edgeR package. Based on the median value of the risk score in the all-sample cohort, all the included patients with OSCC were divided into either high- or low-risk groups, and Kaplan-Meier analysis was performed. The ROC curve was used to verify the accuracy of the risk signature in predicting the prognosis of OSCC. By univariable Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox analyses, we constructed a hsa_circ_0112879-related miRNAs risk model to forecast the prognosis of OSCC. Results: The expression of hsa_circ_0112879 was significantly downregulated in the OSCC tissues and cell lines. The expression level was statistically correlated with the pathological differentiation of OSCC tumors (P=0.0285). Furthermore, 141 differentially expressed hsa_circ_0112879-related miRNAs were obtained [|log2FC| >1, false discovery rate (FDR) <0.05], of which 70 miRNAs were up-regulated in OSCC tissues, whereas 71 miRNAs were down-regulated in OSCC tissues. The area under the ROC curve (AUC) at 1-, 3-, and 5-year in the all-sample cohort was 0.591, 0.689, and 0.618, respectively. The toll-like receptor signaling pathway, Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway, and T-cell receptor (TCR) signaling pathway were mainly enriched in the high-risk group. Conclusions: The model and nomogram constructed herein has the ability to discriminate the prognosis of OSCC patients. Hsa_circ_0112879 may serve as a novel biomarker in the diagnosis and prognosis of OSCC.

Erratum: [Corrigendum] Inhibition of human oral squamous cell carcinoma proliferation and migration by prodrug­activating suicide gene therapies.

[This corrects the article DOI: 10.3892/etm.2023.11790.].

Inhibition of human oral squamous cell carcinoma proliferation and migration by prodrug-activating suicide gene therapies.

Head and neck squamous cell carcinoma (HNSCC), which originates from mucosal epithelium in the oral cavity, pharynx and larynx, is the sixth most common malignancy in the world. The prognosis of HNSCC is not satisfactory due to metastasis, resulting in 5-year survival rates ranging from 65.9 to 67.2%. Previously, we developed a method to evaluate the effect prodrug-activating suicide gene (PA-SG) therapy on the proliferation of HNSCC. The present study investigated PA-SG therapy on metastatic HNSCC by wound-healing assay and our previously established method. HSC-3 cells with stable expression of suicide genes thymidine kinase (TK) or cytosine deaminase (CD) were treated with prodrugs ganciclovir (GCV) or 5-fluorocytosine (5-FC), respectively. Both GCV and 5-FC inhibited HSC-3 proliferation while the bystander effect of CD/5-FC was greater compared with that of TK/GCV. GCV showed a greater anti-migration effect compared with that of 5-FC. To the best of our knowledge, the present study is the first to evaluate the anti-migratory and anti-proliferative effects of PA-SG therapies on metastatic HNSCC. This may also serve as a general method to quantify other types of PA-SC therapy. The present results demonstrated that PA-SG therapy is a promising treatment for anti-metastatic HNSCC therapy development.

CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma.

In oral squamous cell carcinoma (OSCC), a highly aggressive and frequently lethal malignancy, the role and action mechanism of the microtubule regulatory protein CDK5RAP2 have not been fully understood. Here, we show that CDK5RAP2 is highly expressed in OSCC and its expression correlates with clinical stage and lymph node metastasis of the disease. The expression of CDK5RAP2 is regulated by the Wnt signaling pathway. Depletion of CDK5RAP2 inhibits the tumorigenesis and migration of OSCC cells and alters the OSCC cancer stem (-like) cell (CSC) signature. Notably, suppression of CDK5RAP2 expression disrupts spindle orientation during mitosis. Collectively, these results identify CDK5RAP2 as a potential CSC marker and reveal a mechanism that controls the CSC population in OSCC.

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis.

Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy. Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan. Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment. Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:-12.38 to -5.59); diastolic blood pressure (MD = 5.74, 95%CI:-7.20 to -4.29)], serum creatinine (MD = -17.32, 95%CI:-20.55 to -14.10), blood urea nitrogen (MD = -1.89, 95%CI:-3.76 to -0.01), urine microalbumin (MD = -23.90, 95%CI:-26.54 to -21.26), and urinary protein to creatinine ratio (MD = -1.92, 95%CI:-2.15 to -1.69), cystatin C (MD = -1.04, 95%CI: -1.63 to -0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low. Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256.

Interactions among maternal smoking, breastfeeding, and offspring genetic factors on the risk of adult-onset hypertension.

BACKGROUND: Previous studies have reported that maternal smoking during pregnancy and breastfeeding may affect the occurrence of hypertension, but whether early life factors modify the impact of the offspring's genetic risk on hypertension is still unknown. The aim of this study was to investigate the relationships among maternal smoking and breastfeeding with adult-onset hypertension and the modified impact of offspring genetic susceptibility. METHODS: This study included 437,185 participants from the UK Biobank who were initially free of hypertension and provided a prospective cohort of individuals aged 40 to 69 years. The association of maternal smoking during pregnancy and breastfeeding with hypertension was examined by using the Cox regression model. Then, a polygenic risk score (PRS) for hypertension was used to test the gene-environmental interaction on hypertension. RESULTS: During a median follow-up period of 8.7 years, a total of 68,148 cases of hypertension were identified in this study. The hazard ratios (HRs) and 95% confidence intervals (CIs) of hypertension for maternal smoking and breastfeeding were 1.11 (1.09, 1.13) and 0.96 (0.94, 0.98), respectively. However, no evidence of an interaction between maternal smoking and breastfeeding was observed. Across all levels of genetic risk, including high genetic risk, maternal smoking and nonbreastfeeding had higher hypertension hazards than nonmaternal smoking and breastfeeding, respectively. The adjusted HRs (95% CIs) of hypertension were 1.80 (1.73, 1.87) in those who had high genetic predisposition plus maternal smoking and 1.67 (1.60-1.74) in those with nonbreastfeeding and high genetic risk. There were significant additive interactions between maternal smoking or breastfeeding and genetic factors on the incidence of hypertension. CONCLUSIONS: Maternal smoking and nonbreastfeeding were associated with a higher risk of hypertension in adulthood and may attenuate the risk of hypertension related to genetic factors. These results suggested that adherence to nonmaternal smoking and breastfeeding was associated with a lower risk of hypertension among participants with all gradients of genetic risk.

Protective effects of Salvianolic acid B on rat ferroptosis in myocardial infarction through upregulating the Nrf2 signaling pathway.

Accumulating evidence has highlighted the role of ferroptosis, a novel type of programmed cell death involved in the pathological process of myocardial infarction (MI). However, the underlying mechanism of ferroptosis in mediating MI is complicated that needs to be further investigated. Salvianolic acid B (Sal B) extracted from the traditional Chinese medicine (TCM) herb Salvia miltiorrhiza possesses pharmacological function against MI, which provides us with a new direction to explore the effect of Sal B on ferroptosis after myocardial ischemic injury. In the present study, iron accumulation and expression levels of ferroptosis-related proteins in MI rats altered in a time-dependent manner. Importantly, treatment of ferroptosis inhibitors ferrostatin-1 (Fer-1) or deferoxamine (DFO) reversed typical changes of ferroptosis, including iron overload, lipid peroxide accumulation, mitochondrial damage, and specific expression levels of ferroptosis-related proteins, thereby alleviating myocardial injury in rats. Similar results were observed in Sal B-treated MI rats in a dose-dependent manner. In addition, NFE2-related factor 2 (Nrf2) was strongly activated by the treatment of Sal B. In vivo knockdown of Nrf2 in MI rats enhanced ferroptosis and damaged the protective effect of Sal B on MI. Furthermore, Sal B administration was unable to significantly reverse expression levels of target genes of Nrf2 that were associated with iron homeostasis and oxidative stress (e.g., HO-1, xCT, Gpx4, Fth1, and Fpn1) in MI rats after knockdown of Nrf2. Taken together, Sal B contributed to protecting MI by inhibiting ferroptosis via activating the Nrf2 signaling pathway.

Melatonin attenuates polystyrene microplastics induced motor neurodevelopmental defect in zebrafish (Danio rerio) by activating nrf2 - isl2a Axis.

Microplastics, a new type of ecological pollutant, have now become a major environmental concern worldwide. Polystyrene microplastics (PS), one of the most abundant form of microplastics, cause deleterious effects across species. Melatonin (MT), which is secreted by pineal gland, exhibits protective role against pollutant-induced damage. However, whether MT could ameliorate PS-induced neurodevelopmental toxicity remain unclear. In our study, zebrafish embryos were treated with PS (0.5, 25 mg/L) in the presence or absence of MT (1 µM) from 4 h post-fertilization (hpf) to 144 hpf. Locomotion behavior, oxidative stress, apoptosis, proliferation and development of caudal primary (Cap) motoneuron axon were analyzed. Gene expression was determined by qRT-PCR or whole-mount in situ hybridization. Results showed that PS exposure significantly reduced swimming speed of zebrafish larvae and induced excessive reactive oxygen species (ROS), apoptosis and aberrant proliferation. In addition, PS treatment markedly shortened the length of Cap motoneuron axons and decreased expression of neurodevelopment related genes. While, MT administration considerably rescued the neurodevelopmental toxicity of PS. Mechanistically, MT activated nrf2 (nuclear factor-E2-related factor 2) - isl2a (ISL LIM homeobox 2a) axis to antagonize the side effects of PS. In all, our findings suggest that PS exposure during early life lead to aberrant neurodevelopment of zebrafish, and MT might be a therapeutic option for protecting such disorder.

Geniposide Possesses the Protective Effect on Myocardial Injury by Inhibiting Oxidative Stress and Ferroptosis via Activation of the Grsf1/GPx4 Axis.

Reactive oxygen species (ROS) produced in the ischemic myocardium can induce cardiomyocyte injury and death, resulting in cardiac remodeling. Ferroptosis, known as a newly type of cell death caused by iron-dependent oxidative stress, which is an essential death mechanism in cardiomyocytes. However, it is unclear whether oxidative stress products can further induce ferroptosis and aggravate cardiomyocyte injury. Geniposide (GEN), a major active component of Gardenia jasminoides J. Ellis, possesses the natural antioxidant activity and cardioprotective effect. Herein, we evaluated the role of ferroptosis in myocardial oxidative injury and the protective effect of GEN on myocardial ferroptosis. We first detected iron overload, massive ROS, and lipid peroxidation in ferric ammonium citrate (FAC)-treated cardiomyocytes, which were typical characteristics of ferroptosis. The iron overload-induced oxidative stress and ferroptosis aggravated cardiomyocyte injury, which were significantly alleviated by GEN treatment. Similar phenotypic changes of ferroptosis were consistently discovered in hydrogen peroxide (H2O2)-induced cells, which were reversed by GEN treatment as well. Interestingly, the RNA-binding protein Grsf1, which directly upregulated Gpx4 at the translational level, was activated by GEN following myocardial oxidative injury. The specific knockdown of Grsf1 increased their sensitivity to ferroptosis and weakened the cardioprotective effect of GEN in H2O2-treated cardiomyocytes. Moreover, GEN treatment reduced iron overload and lipid peroxidation in myocardial infarction (MI) rats, thereby fighting against the cardiac ischemic injury. Collectively, our study revealed the pathogenesis of oxidative stress and ferroptosis associated with myocardial ischemia, and indicated the antioxidant and anti-ferroptosis effects of GEN on preventing myocardial injury by activating the Grsf1/GPx4 axis, serving as a potential therapeutic target.

Molybdenum Diphosphide Nanorods with Laser-Potentiated Peroxidase Catalytic/Mild-Photothermal Therapy of Oral Cancer.

Chemodynamic therapy (CDT) is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide (H2O2) into hydroxyl radical (•OH) via Fenton or Fenton-like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor-specificity and minimal-invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser-potentiated peroxidase catalytic/mild-photothermal therapy of molybdenum diphosphide nanorods (MoP2 NRs) is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti-infection. In this system, MoP2 NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP2 NRs act as photosensitizers to efficiently capture the photo-excited band electrons and valance band holes, exhibiting enhanced peroxidase-like catalytic activity to sustainedly decompose tumor endogenous H2O2 to •OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications.

Retraction Notice to: circPHIP promotes oral squamous cell carcinoma progression by sponging miR-142-5p and regulating PHIP and ACTN4 expression.

[This retracts the article DOI: 10.1016/j.omtn.2020.10.038.].

Familial left cervical neurofibromatosis 1 with scoliosis: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder affecting many parts of the body with café au lait spots, skeletal deformity, and scoliosis. A familial case of NF1 with scoliosis and a painless mass had not yet been reported. CASE SUMMARY: We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis. His right shoulder was about 5 cm lower than the left, the left side of his face was deformed, and the left submandibular skin was relaxed. The folding and drooping were obvious and movement was poor. Computed tomography revealed the involvement of the neck, upper chest wall, and surrounding left shoulder, accompanied by bone changes and scoliosis. Histological evaluation showed subepidermal pale blue mucoid degeneration, fibrous fusiform cells in the dermis in a fascicular, woven arrangement. His mother had the same medical history. The diagnosis was neurofibromatosis of the left neck. Various parts of the tumor tissue were serially resected during several visits. Eight months after surgery, there was a slight tendency to regrow. CONCLUSION: This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient's growth and development.

Quantitative evaluation and comparison of two prodrug-activating suicide gene therapies on oral squamous cell carcinoma.

Prodrug-activating suicide gene therapy (PA suicide gene therapy for short) for cancer is to introduce cancer cells with suicide genes. The enzyme encoded by suicide gene is not toxic but is able to kill cancer cells by converting a non-toxic prodrug into a toxic compound. This approach is a promising cancer gene therapy that could reduce non-specific toxicity to normal tissue. However, there is no quantitative method to evaluate efficacy of suicide gene therapy in preclinical study. The aim of this study is to develop a new method to quantitatively evaluate and compare prodrug-activating suicide gene therapies. This study was carried out on an oral squamous cell carcinoma (OSCC) cell line CAL-27. Suicide genes were integrated into ROSA26 locus of CAL-27 by CRISPR-Cas9. CAL-27 cell lines stably expressing herpes simplex virus-thymidine kinase (TK) or yeast cytosine deaminase (CD) were used to evaluate and compare PA suicide gene therapies. The efficacies of PA suicide gene therapies were quantitatively evaluated from three aspects: effective prodrug concentration, prodrug treatment time, and bystander effect. This method also could be used for different types of suicide gene therapies and different types of cancer. When the prodrug concentration, treatment time, and rate of suicide gene-positive cells (related to bystander effect) are fixed, anti-cancer effects could be quantitatively measured. This information is important for suicide gene therapy preclinical development.

Comprehensive co-expression analysis reveals TMC8 as a prognostic immune-associated gene in head and neck squamous cancer.

The occurrence and prognosis of head and neck squamous cell cancer (HNSC) is closely associated with human papillomavirus (HPV) infection. Transmembrane channel-like 8 (TMC8) is a key gene affecting the susceptibility of HPV and that plays an important role in T cell regulation. However, the mechanism by which TMC8 affects T cells and whether it further affects the prognosis of patients with HNSC remains unclear. In the present study, oral cancer cell lines and independent tumor specimens were used to detect TMC8 expression in HNSC. Differential expression of TMC8, methylation status, function and associated signaling pathways were further analyzed. Then, multiple databases were cross-analyzed for the relationship of TMC8 with immune cell infiltration and its impact on the prognosis of numerous types of cancer. The results showed that TMC8 was upregulated in HNSC and high expression was predictive of an improved prognosis. Furthermore, TMC8 was concentrated in multiple immune-associated signaling pathways and the expression of TMC8 was associated with the infiltration of CD4+ T cells and their subsets, including CD8+ T cells, B cells and macrophages, suggesting that TMC8 may play an anti-HPV role by regulating CD4+ T cells. Thus, TMC8 plays an anti-HPV role by regulating the infiltration level of CD4+ T cells, and could therefore be used as a potential prognostic marker for patients with HNSC.

Downregulated hsa_circ_0036988 promotes proliferation and metastasis in oral squamous cell carcinoma.

BACKGROUND: As a novel class of endogenous ncRNAs, Circular RNAs (circRNAs) have been verified to be involved in the carcinogenesis and tumor progression. OBJECTIVE: This study aimed to investigate the potential function of a candidate circRNA hsa_circ_0036988 in oral squamous cell carcinoma (OSCC). METHODS: The altered expression of hsa_circ_0036988 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in OSCC samples and OSCC cell lines. The associations between the levels of hsa_circ_0036988 and the clinicopathological features were statistically analysed. The function of hsa_circ_0036988 in OSCC were evaluated via a series of in vitro experiments by using constructed plasmids or siRNA. Western blotting assays were conducted to evaluate changes in protein expression levels. RESULTS: Hsa_circ_0036988 was significantly downregulated in OSCC tissues compared with adjacent normal tissues. While low expression of hsa_circ_0036988 was highly correlated with lymph nodes metastasis. Overexpression or knockdown of hsa_circ_0036988 significantly affected the proliferation, migration and invasion of OSCC cells. Furthermore, the altered expression of hsa_circ_0036988 have an impact on the epithelial-to-mesenchymal transition (EMT)-related protein expression levels. CONCLUSIONS: Our findings indicated that hsa_circ_0036988 may affect cell proliferation, migration and invasion by regulating EMT progress, which might provide a therapeutic strategy for the treatment of OSCC.

Therapeutic Hypothermia Mitigates the Sepsis-Increased Permeability in EA. hy926 Cells by Preserving Rap1 Expression.

To determine the effect and potential mechanisms of therapeutic hypothermia (TH) on the permeability of septic cells. Human EA. hy926 cells were transfected with, or without, control or ras-proximate-1 (Rap1)-specific siRNA and treated with 2 µg/mL of lipopolysaccharide (LPS). The cells were cultured in normal temperature (NT) or a temporary TH for 10 hours. The cellular permeability of each group of cells was determined by transwell permeability assay. The relative levels of Rap1, RhoA (a small GTP enzyme of the Rho family), VE-cadherin expression, and myosin light chain (MLC) phosphorylation were quantified by Western blot and immunofluorescent assays. Compared with the control group, LPS stimulation increased cellular permeability in EA. hy926 cells under an NT condition, but significantly mitigated by TH. The effect of TH decreased after Rap1 silencing. Furthermore, LPS upregulated RhoA expression and MLC phosphorylation, but reduced Rap1 and VE-cadherin expression, which were also enhanced by Rap1 silencing, but significantly mitigated by TH. Immunofluorescent analyses indicated that LPS significantly increased phosphorylated MLC, but decreased VE-cadherin expression, which were further deteriorated by Rap1 silencing, but significantly mitigated by TH in EA. hy926 cells. TH significantly mitigated the sepsis-increased permeability of EA. hy926 cells by enhancing the Rap1 expression to attenuate the RhoA/MLC signaling.

Comprehensive analysis of macrophage-related multigene signature in the tumor microenvironment of head and neck squamous cancer.

Macrophages are among the most abundant cells of the tumor microenvironment in head and neck squamous cancer (HNSC). Although the marker gene sets of macrophages have been found, the mechanism by which they affect macrophages and whether they further predict the clinical outcome is unclear. In this study, a univariate COX analysis and a random forest algorithm were used to construct a prognostic model. Differential expression of the key gene, methylation status, function, and signaling pathways were further analyzed. We cross-analyzed multiple databases to detect the relationship between the most critical gene and the infiltration of multiple immune cells, as well as its impact on the prognosis of pan-cancer. FANCE is recognized as hub gene by different algorithms. It was overexpressed in HNSC, and high expression was predictive of better prognosis. It might promote apoptosis through the Wnt/ß-catenin pathway. The expression of FANCE is inversely proportional to the infiltration of CD4 + T cells and their subsets, tumor-associated macrophages (TAMs), M2 macrophages, but positively co-expressed with M1 macrophages. In summary, FANCE was identified as the hub gene from the macrophage marker gene set, and it may improve the prognosis of HNSC patients by inhibiting lymphocytes and tumor-associated macrophages infiltration.