FAT1 as a tumor mutation burden specific gene affects the immunotherapy effect in head and neck squamous cell cancer.

BACKGROUND: Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. METHODS: A total of 33 HNSCC patients were enrolled in this study. We calculated the TMB score based on next-generation sequencing (NGS) sequencing and grouped these patients based on TMB score. Then, we examined the immune microenvironment of HNSCC using assessments of the bulk transcriptome and the single-cell RNA sequence (scRNA-seq) focusing on the molecular nature of TMB and mutations in HNSCC from our cohort. The association of the mutation pattern and TMB was analyzed in The Cancer Genome Atlas (TCGA) and validated by our cohort. RESULTS: 33 HNSCC patients were divided into three groups (TMB-low, -medium, and -high) based on TMB score. In the result of 520-gene panel sequencing data, we found that FAT1 and LRP1B mutations were highly prevalent in TMB-high patients. FAT1 mutations are associated with resistance to immunotherapy in HNSCC patients. This involves many metabolism-related pathways like RERE, AIRE, HOMER1, etc. In the scRNA-seq data, regulatory T cells (Tregs), monocytes, and DCs were found mainly enriched in TMB-high samples. CONCLUSION: Our analysis unraveled the FAT1 gene as an assistant predictor when we use TMB as a biomarker of drug resistance in HNSCC. Tregs, monocytes, and dendritic cells (DCs) were found mainly enriched in TMB-high samples.

Next-generation sequencing identified that RET variation associates with lymph node metastasis and the immune microenvironment in thyroid papillary carcinoma.

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA. Nodal metastasis is an unfavorable predictor. Exploring the underlying mechanism may bring a deep insight into THCA. METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited. It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC). The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment. A pathway enrichment analysis was used to explore the underlying mechanism. RESULTS: Gene alteration was frequent in THCA. BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes. RET variation was positively related to nodal metastasis in PTC. RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc. Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation. A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways. CONCLUSION: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer: a clinical next-generation sequencing study.

Background: TP53 mutations and homologous recombination deficiency (HRD) occur frequently in breast cancer. However, the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not clear. Methods: Clinical next-generation sequencing (NGS) of both tumor and paired blood DNA from 119 breast cancer patients (BRCA-119 cohort) was performed with a 520-gene panel. Mutations, tumor mutation burden (TMB), and genomic HRD scores were assessed from NGS data. NGS data from 47 breast cancer patients in the HRD test cohort were analyzed for further verification. Results: All TP53 pathogenic mutations in patients had somatic origin, which was associated with the protein expression of estrogen receptor and progestogen receptor. Compared to patients without TP53 pathologic mutations, patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic alterations. The frequency of TP53 pathologic mutation was higher in the HRD-high group (HRD score ≥ 42) relative to that in the HRD-low group (HRD score < 42). TP53 has different mutational characteristics between the HRD-low and HRD-high groups. TP53-specific mutation subgroups had diverse genomic features and TMB. Notably, TP53 pathogenic mutations predicted the HRD status of breast cancer patients with an area under the curve (AUC) of 0.61. TP53-specific mutations, namely HRD-low mutation, HRD-high mutation, and HRD common mutation, predicted the HRD status of breast cancer patients with AUC values of 0.32, 0.72, and 0.58, respectively. Interestingly, TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values (0.80) in predicting HRD status. Conclusions: TP53-specific mutation combinations predict the HRD status of patients, indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase (PARP) inhibitors in breast cancer patients .

Activation of Bivalent Gene POU4F1 Promotes and Maintains Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is the most aggressive molecular subtype of breast cancer with worse prognosis and fewer treatment options. The underlying mechanisms upon BLBC transcriptional dysregulation and its upstream transcription factors (TFs) remain unclear. Here, among the hyperactive candidate TFs of BLBC identified by bioinformatic analysis, POU4F1 is uniquely upregulated in BLBC and is associated with poor prognosis. POU4F1 is necessary for the tumor growth and malignant phenotypes of BLBC through regulating G1/S transition by direct binding at the promoter of CDK2 and CCND1. More importantly, POU4F1 maintains BLBC identity by repressing ERα expression through CDK2-mediated EZH2 phosphorylation and subsequent H3K27me3 modification in ESR1 promoter. Knocking out POU4F1 in BLBC cells reactivates functional ERα expression, rendering BLBC sensitive to tamoxifen treatment. In-depth epigenetic analysis reveals that the subtype-specific re-configuration and activation of the bivalent chromatin in the POU4F1 promoter contributes to its unique expression in BLBC, which is maintained by DNA demethylase TET1. Together, these results reveal a subtype-specific epigenetically activated TF with critical role in promoting and maintaining BLBC, suggesting that POU4F1 is a potential therapeutic target for BLBC.

Somatic mutations in four novel genes contribute to homologous recombination deficiency in breast cancer: a real-world clinical tumor sequencing study.

Breast cancers involving mutations in homologous recombination (HR) genes, most commonly BRCA1 and BRCA2 (BRCA1/2), respond well to PARP inhibitors and platinum-based chemotherapy. However, except for these specific HR genes, it is not clear which other mutations contribute to homologous recombination defects (HRD). Here, we performed next-generation sequencing of tumor tissues and matched blood samples from 119 breast cancer patients using the OncoScreen Plus panel. Genomic mutation characteristics and HRD scores were analyzed. In the HR genes, we found that BRCA1/2 and PLAB2 mutations were related to HRD. HRD was also detected in a subset of patients without germline or somatic mutations in BRCA1/2, PLAB2, or other HR-related genes. Notably, LRP1B, NOTCH3, GATA2, and CARD11 (abbreviated as LNGC) mutations were associated with high HRD scores in breast cancer patients. Furthermore, functional experiments demonstrated that silencing CARD11 and GATA2 impairs HR repair efficiency and enhances the sensitivity of tumor cells to olaparib treatment. In summary, in the absence of mutations in the HR genes, the sensitivity of tumor cells to PARP inhibitors and platinum-based chemotherapy may be enhanced in a subset of breast cancer patients with LNGC somatic mutations.

Identification and validation of a gap junction protein related signature for predicting the prognosis of renal clear cell carcinoma.

Background: Gap junction proteins (GJPs) are a class of channel proteins that are closely related to cell communication and tumor development. The objective of this study was to screen out GJPs related prognostic signatures (GRPS) associated with clear cell renal cell carcinoma (ccRCC). Materials and Methods: GJPs microarray data for ccRCC patients were obtained from The Gene Expression Omnibus (GEO) database, along with RNA sequencing data for tumor and paired normal tissues from The Cancer Genome Atlas (TCGA) database. In the TCGA database, least absolute shrinkage and selection Operator (LASSO) and Cox regression models were used to identify GJPs with independent prognostic effects as GRPS in ccRCC patients. According to the GRPS expression and regression coefficient from the multivariate Cox regression model, the risk score (RS) of each ccRCC patient was calculated, to construct the RS prognostic model to predict survival. Overall survival (OS) and progression-free survival (PFS) analyses; gene pan-cancer analysis; single gene survival analysis; gene joint effect analysis; functional enrichment analysis; tumor microenvironment (TME) analysis; tumor mutational burden (TMB) analysis; and drug sensitivity analysis were used to explore the biological function, mechanism of action and clinical significance of GRPS in ccRCC. Further verification of the genetic signature was performed with data from the GEO database. Finally, the cytofunctional experiments were used to verify the biological significance of GRPS associated GJPs in ccRCC cell lines. Results: GJA5 and GJB1, which are GRPS markers of ccRCC patients, were identified through LASSO and Cox regression models. Low expression of GJA5 and GJB1 is associated with poor patient prognosis. Patients with high-RS had significantly shorter OS and PFS than patients with low-RS (p< 0.001). The risk of death for individuals with high-RS was 1.695 times greater than that for those with low-RS (HR = 1.695, 95%CI= 1.439-1.996, p< 0.001). Receiver Operating Characteristic (ROC) curve showed the great predictive power of the RS prognostic model for the survival rate of patients. The area under curve (AUC) values for predicting 1-year, 3-year and 5-year survival rates were 0.740, 0.781 and 0.771, respectively. The clinical column chart was also reliable for predicting the survival rate of patients, with AUC values of 0.859, 0.846 and 0.796 for predicting 1-year, 3-year and 5-year survival, respectively. The GRPS was associated with immune cell infiltration, the TME, the TMB, and sensitivity to chemotherapy drugs. Further in vitro experiments showed that knockdown of GJA5 or GJB1 could promote the proliferation, migration and epithelial-mesenchymal transition (EMT) and inhibit apoptosis of ccRCC cells. Conclusion: GJA5 and GJB1 could be potential biological markers for predicting survival in patients with ccRCC.

Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.

Relativistic-guided stable mode of few-cycle 20 µm level infrared radiation.

The generation of intense infrared radiation with a wavelength greater than 10 µm is limited by the optical materials in traditional methods or the laser-plasma parameters of plasma-bubble methods. In this study, we propose a new method for generating an intense longitudinal radiation field of tens of GV/m. By utilizing the oscillations of the electron film on the inner surface of the micro-tube, excited by the relativistic electron beam propagating within it, it is possible to obtain tunable long-wavelength few-cycle infrared radiation, ranging from 20 to 30 µm and even longer. The radiation source is guided entirely by a relativistic electron beam and formed a stable TM propagation mode in the micro-tube. This opens up new opportunities for applications of the relativistic intensity infrared radiation to high-field physics, shorter attosecond pulses generation and charged particle acceleration.

[Tislelizumab monotherapy for the treatment of recurrent/metastatic head and neck squamous cell carcinoma].

Objective:The aim of this retrospective study is to evaluate the safety and efficacy of tislelizumab in patients with recurrent/metastatic head and neck squamous cell carcinoma. Methods:Six patients with recurrent/metastatic head and neck squamous cell carcinoma who received tislelizumab monotherapy in our hospital from 2018 to 2020 were retrospectively analyzed. The information of sex, age, TNM stage, efficacy, and adverse reactions were collected. All patients were recruited from the RATIONALE 102 study. The primary end point was the objective response rate, and other end points included progression-free survival and overall survival. We performed tumor immune-related gene sequencing and transcriptome sequencing analysis on the tumor tissues of the patient, and used bioinformatics methods to enrich immune cells and analyze signaling pathways. All analyses were performed using R 4.1. 0 software, SPSS Statistics 24.0 software and GraphPad Prism 8. Results:As of May 31, 2020, the median follow-up time was 26.35 months. The objective response rate with tislelizumab was 50.0%, the median progression-free survival was 6.44 months, and the estimated median survival was 20.07 months. The incidence of grade 3 or higher adverse reactions was 66.7%, including hyponatremia, hypokalemia, hypercalcemia, etc. The expression of macrophage, Treg and neutrophil-related genes are higher in immune-sensitive patients, and the signaling pathways of the intestinal immune network for IgA production, graft versus host disease and autoimmune thyroid disease are significantly activated. Conclusion:Tislelizumab was found to be controllable and tolerable in patients with recurrent/metastatic head and neck squamous cell carcinoma. The response to tislelizumab is related to immune cell infiltration and activation of immune-related signaling pathways.

C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2.

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48's function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

Abnormal genetic and epigenetic patterns of m6A regulators associated with tumor microenvironment in colorectal cancer.

Background: N6-methyladenosine (m6A) has a critical role in the development and progression of cancer. However, the genetic and epigenetic patterns, as well as tumor microenvironment (TME) infiltration characteristics of m6A regulators in colorectal cancer (CRC) remain largely unknown. Methods: Molecular patterns of m6A modifications of 24 m6A regulators in CRC samples were evaluated using data from The Cancer Genome Atlas (TCGA). Mutations, copy number variations (CNVs), DNA methylation, and chromatin accessibility were examined to investigate the underlying mechanisms of the aberrant expression of m6A regulators. Correlations between m6A-related genes and TME cell-infiltrating characteristics were evaluated using Tumor Immune Estimation Resource (TIMER). Results: The m6A regulators were frequently dysregulated in CRC, with two downregulated and 16 upregulated. All the m6A regulators had mutations (frequency ranging from 0.9% to 7%), with active mutations tending to occur in RBM15 and inactive mutations in ZC3H13. Only five m6A regulators had CNV frequency greater than 1%: YTHDC2 (2.4%), YTHDF1 (7.0%), YTHDF3 (1.9%), VIRMA (1.7%), and ZC3H13 (3.0%). The copy numbers of these five genes were positively correlated with their expression levels. The m6A regulators frequently showed imbalanced methylation in CRC, with hypomethylation of YTHDF2, IGF2BP3, FTO, and hypermethylation of HNRNPC, METTL3, and WTAP. Most m6A regulators had high chromatin accessibility, which was positively correlated with their gene expression. IGF2BP1 was identified as an independent prognostic factor for overall survival. Moreover, the expression of most m6A regulators was positively correlated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: Aberrant expression of m6A regulators is associated with mutation, CNV, and chromatin accessibility, owing to both genetic and epigenetic modifications. The TME infiltration characterization of m6A regulators could guide the development of more effective immunotherapy strategies in CRC.

The dose-related plateau effect of surviving fraction in normal tissue during the ultra-high-dose-rate radiotherapy.

Objective.Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared with conventional dose-rate radiotherapy. The transient hypoxia may be a vital explanation for sparing the normal tissue. The heterogeneity of oxygen distribution for different doses and dose rates in the different radiotherapy schemes are analyzed. With these results, the influence of doses and dose rates on cell survival are evaluated in this work.Approach.The two-dimensional reaction-diffusion equations are used to describe the heterogeneity of the oxygen distribution in capillaries and tissue. A modified linear quadratic model is employed to characterize the surviving fraction at different doses and dose rates.Main results.The reduction of the damage to the normal tissue can be observed if the doses exceeds a minimum dose threshold under the ultra-high-dose-rate radiation. Also, the surviving fraction exhibits the 'plateau effect' under the ultra-high dose rates radiation, which signifies that within a specific range of doses, the surviving fraction either exhibits minimal variation or increases with the dose. For a given dose, the surviving fraction increases with the dose rate until tending to a stable value, which means that the protection in normal tissue reaches saturation.Significance.The emergence of the 'plateau effect' allows delivering the higher doses while minimizing damage to normal tissue. It is necessary to develop appropriate program of doses and dose rates for different irradiated tissue to achieve more efficient protection.

Significant fibrosis assessed by liver biopsy among Chinese bariatric surgery patients: A prospective cross-sectional study.

Background: Fibrosis stages affect clinical prognoses related to nonalcoholic fatty liver disease (NAFLD). However, data on the prevalence and clinical features of significant fibrosis are scarce in Chinese bariatric surgery patients. We aimed to investigate the prevalence of significant fibrosis in bariatric surgery patients and to identify its predictors. Methods: We prospectively enrolled the patients performing intra-operative liver biopsies during bariatric surgery from a bariatric surgery center in a university hospital between May 2020 and January 2022. Anthropometric characteristics, co-morbidities, laboratory data and pathology reports were collected and analyzed. The performance of non-invasive models was evaluated. Results: Of 373 patients, 68.9%% had non-alcoholic steatohepatitis (NASH) and 60.9% exhibited fibrosis. Significant fibrosis was present in 9.1% of patients, advanced fibrosis in 4.0%, and cirrhosis in 1.6%. Multivariate logistic regression showed that increasing age (odds ratio [OR], 1.06; p=0.003), presence of diabetes (OR, 2.62; p=0.019), elevated c- peptide (OR, 1.26; p=0.025) and elevated aspartate aminotransferase (AST) (OR, 1.02; p=0.004) were independent predictors of significant fibrosis. The non-invasive models, AST to Platelet ratio (APRI), Fibrosis-4 (FIB-4), and Hepamet fibrosis scores (HFS) provided greater accuracy for predicting significant fibrosis, compared to the NAFLD Fibrosis Score (NFS) and BARD score. Conclusion: More than two-thirds of bariatric surgery patients had NASH and the prevalence of significant fibrosis was high. Elevated levels of AST and c- peptide, advanced age and diabetes indicated a higher risk of significant fibrosis. Non-invasive models, APRI, FIB-4 and HFS can be used to identify significant liver fibrosis in bariatric surgery patients.

Comparison of lateral transperitoneal versus retroperitoneal laparoscopic adrenalectomy for pheochromocytoma: a single-centre retrospective study.

Laparoscopic adrenalectomy (LA) has became the standardized treatment for pheochromocytoma. The aim of this study was to evaluate outcomes of lateral transperitoneal and retroperitoneal LA for pheochromocytoma. Between January 2011 and December 2021, 142 patients with pheochromocytoma underwent LA via lateral transperitoneal (123 patients) or retroperitoneal (19 patients) approaches. Data of these patients were assessed to investigate the differences in perioperative outcomes and intraoperative haemodynamic parameters between the two procedures. Clinical parameters at presentation were comparable between the two groups, except for tumour size, which was larger in the transperitoneal group (50 [10-115] mm vs 35 [7-110] mm, P = 0.012). There were no significant differences between the two groups in terms of operation time, estimated blood loss, intraoperative transfusion rate, incidence of complications, conversion to open surgery, postoperative analgesic requirement, time to first oral intake, or mean hospital stay. Intraoperative haemodynamic parameters of the two groups were similar. After adjusting for tumour size using propensity score matching, both perioperative outcomes and haemodynamic parameters were still comparable. Lateral transperitoneal and retroperitoneal laparoscopic adrenalectomies provide similar perioperative and haemodynamic outcomes for surgical resection of pheochromocytoma.

Cancer associated fibroblast derived gene signature determines cancer subtypes and prognostic model construction in head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are the most common type of head and neck cancer with an unimproved prognosis over the past decades. Although the role of cancer-associated-fibroblast (CAF) has been demonstrated in HNSCC, the correlation between CAF-derived gene expression and patient prognosis remains unknown. METHODS: A total of 528 patients from TCGA database and 270 patients from GSE65858 database were contained in this study. After extracting 66 CAF-related gene expression data from TCGA database, consensus clustering was performed to identify different HNSCC subtypes. Limma package was used to distinguish the differentially expression genes (DEGs) between these subtypes, followed by Lasso regression analysis to construct a prognostic model. The model was validated by performing Kaplan-Meier survival, ROC and risk curve, univariate and multivariate COX regression analysis. GO, KEGG, GSEA, ESTIMATE and ssGSEA analyses was performed to explort the potential mechanism leading to different prognosis. RESULTS: Based on the 66 CAF-related gene expression pattern we stratitied HNSCC patients into two previously unreported subtypes with different clinical outcomes. A prognostic model composed of 15 DEGs was constructed and validated. In addition, bioinformatics analysis showed that the prognostic risk of HNSCC patients was also negatively correlated to immune infiltration, implying the role of tumor immune escape in HNSCC prognosis and treatment option. CONCLUSIONS: The study develops a reliable prognostic prediction tool and provides a theoretical treatment guidance for HNSCC patients.

Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas.

Background: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. Methods: To identify N6-methyladenosine (m6A) regulators that are involved in regulating the HNSCC TME, a computational screen was applied to The Cancer Genome Atlas (TCGA) HNSCC patient samples. The effects of mutation, copy number variation (CNV), and transcriptional regulation on YTHDF1 expression were analyzed. We analyzed the TME infiltration, cancer-immunity cycle activities, and YTHDF1-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: Among the 24 m6A regulators, 3 factors (YTHDF1, ELAVL1, and METTL3) were highly correlated with TME infiltration. As the top candidate, YTHDF1 was up-regulated and amplified in HNSCC. YTHDF1 promoter gains active histone marks and high chromatin accessibility, which might be transcriptionally activated by SOX2 and TP63. Moreover, YTHDF1 expression significantly associates with tumor malignant phenotype in HNSCC, which has a positive correlation with CD4+ T cells and a negative correlation with CD8+ T cells infiltration. Specifically, YTHDF1 expression is negatively associated with the cancer-immunity cycle and immune checkpoint inhibitors. In terms of the underlying biological mechanisms, YTHDF1 may interact with YTHDF2/3 to regulate several vital immune-related pathways. Conclusions: We identify YTHDF1 associated with TME and elucidate an underlying mechanism of immune escape in HNSCC, which might be used as a predictive marker in guiding immunotherapy.

Risk factors for hemodynamic instability during laparoscopic resection of pheochromocytoma.

BACKGROUND: Laparoscopic adrenalectomy for pheochromocytoma is associated with high risk of intraoperative hemodynamic instability. Our study aimed to identify predictive factors for hemodynamic instability during laparoscopic resection of pheochromocytoma. METHODS: Between January 2011 and December 2021, 136 patients underwent unilateral laparoscopic adrenalectomy for pheochromocytoma. The patients were divided into 2 groups depending on the presence or absence of hemodynamic instability during surgery. Intraoperative hemodynamic parameters were compared between the 2 groups. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to intraoperative hemodynamic instability via both univariate analysis and multivariate logistic regression analysis. RESULTS: There was greater blood pressure fluctuations and higher maximum blood pressure and heart rate in the hemodynamic instability group. More patients need intraoperative administration of vasoactive drugs in the hemodynamic instability group. In the univariate analysis, presence of coronary artery disease, tumour size, and previous hypertension history were significantly associated with intraoperative hemodynamic instability. The multivariate logistic regression analysis showed that tumour size and previous hypertension history were independent risk factors for intraoperative hemodynamic instability. CONCLUSION: Tumour size and previous hypertension history were associated with hemodynamic instability during laparoscopic resection of pheochromocytoma.

Schwannomatosis patient who was followed up for fifteen years: A case report.

BACKGROUND: Schwannomatosis is a rare disease characterized by multiple schwannomas of the whole body. Although benign, schwannomatosis that occurs in important areas of the body, such as the brain and spinal canal, can cause considerable disability and mortality. The disease is rare, frequent and relapsing, and this poses a diagnostic and therapeutic challenge. CASE SUMMARY: A 40-year-old male had multiple masses all over his body, starting at the age of 19. Four years prior, he started to experience a progressive decrease in muscle strength in both lower limbs and developed urinary and defecation dysfunctions, and gradual paralysis. One month prior, the patient developed pain and numbness in his left forearm. The patient had undergone five surgical procedures for this disease in our department. Based on the family history, imaging examinations, pathological biopsy and molecular biological examinations, the diagnosis of schwannomatosis was confirmed. This time, the patient was admitted to our hospital again for a 6th operation because of the pain and numbness in his left forearm. After the operation, the patient's symptoms improved significantly; the patient recovered and was discharged from the hospital. At the last telephone follow-up, the patient reported a poor general condition but was alive. CONCLUSION: Here, we report a rare case of schwannomatosis. We conducted 15 years of patient follow-up and treatment, and analyzed the timing of surgery and patient psychology. This case will further extend our overall understanding of the diagnosis and treatment of this rare tumor.