Intratumoral microbiota represents an important component of the tumor microenvironment, but its role in penile cancer remains poorly understood. Here, we performed an integrated multi-kingdom analysis of intratumoral bacteria, fungi, and HPV in 102 primary tumors and 23 matched metastatic lymph nodes using 16S rRNA and ITS sequencing combined with clinical data. We identified distinct microbial characteristics associated with lymph node metastasis, tumor progression, prognosis, and HPV status. Intratumoral bacterial–fungal interaction networks were extensive but progressively weakened during tumor advancement. Notably, an integrated random forest model incorporating both bacterial and fungal features showed better discriminatory performance than single-kingdom models across multiple clinical stratifications. Together, these findings highlight the clinical relevance of the intratumoral microbiota in penile cancer and support a holistic multi-kingdom ecological framework for understanding tumor progression and improving prognostic assessment.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Background Nasopharyngeal carcinoma (NPC) is associated with lymphocyte infiltration; however, the majority of research on NPC has focused on the role of T cells, with relatively little known about the roles of B cells and their subtypes. Therefore, we evaluated the prognostic value of CD20 + B cell density and B-cell subtypes along with their functional enrichment and hub genes in NPC. Methods The prognostic value of CD20 + B-cell density for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) was explored by immunohistochemistry using multivariate analysis. Transcriptomic expression data from Gene Expression Omnibus (GEO) datasets were analyzed to identify B-cell subtypes and their functional enrichment in NPC tissues. Pseudotime trajectory analysis was performed to evaluate the B-cell differentiation trajectory and hub genes were identified using Cytoscape software. Results Patients with NPC exhibiting a high infiltrating density of CD20+ B cells showed significantly better 5-year DMFS, OS, and PFS compared to those of patients with a low infiltrating density. Naïve B cells, switched memory B cells, exhausted B cells, and plasma cells were identified as key B-cell subtypes infiltrating NPC tumors, with naïve B cells showing the highest infiltration levels associated with a better prognosis. Naïve B cells were closely associated with immune pathways and the hub genes were typical markers for T and B cells. Conclusion A high infiltrating density of B cells showed strong prognostic value in patients with NPC. Naïve B cells may play an important role in tumor immunity for NPC.

The hyaluronan-mediated motility receptor (HMMR) is widely expressed across various species and plays a crucial role in cancer progression. However, its role in nasopharyngeal carcinoma (NPC) remains unexplored. Here, we identified a novel HMMR-FAM83D-β-catenin axis, which drives NPC progression through β-catenin signaling. Using bulk RNA sequencing, single-cell RNA-sequencing, and immunohistochemistry, we determined that HMMR is highly expressed in NPC tissues, correlating with poor survival in NPC patients. In vitro assays demonstrated that modulating HMMR expression influenced NPC cell proliferation, migration, and invasion. In vivo, HMMR knockdown significantly inhibited tumor growth and metastasis in NPC models. HMMR was significantly upregulated in NPC tissues and correlated with worse patient survival. Mechanistically, HMMR was found to interact with the Wnt/β-catenin signaling pathway, affecting both pathway activation and β-catenin expression, as evidenced by RNA-seq and western blotting. Co-immunoprecipitation, mass spectrometry, and western blot analyses further revealed that HMMR interacts with Family with Sequence Similarity 83 Member D (FAM83D), stabilizing its expression by inhibiting its ubiquitination. This interaction, in turn, modulates β-catenin levels, driving NPC progression. Our findings reveal a novel HMMR-FAM83D-β-catenin axis that promotes NPC cell progression through Wnt/β-catenin signaling by modulating β-catenin signaling. HMMR could serve as a potential prognostic biomarker and therapeutic target for NPC, deepening our understanding of its role in disease progression.

Glioma is a highly aggressive brain tumor with limited treatment success due to its resistance to conventional therapies. Sirtuin 5 (SIRT5) has emerged as a promising target for cancer therapy, though it exhibits dual roles in different cancer types. In this study, we investigate the role of SIRT5 in glioma and its corresponding mechanisms. Our findings demonstrate that SIRT5 expression is elevated in glioma cells both in vitro and in vivo. SIRT5 knockdown significantly reduced glioma cell proliferation and enhanced sensitivity to ferroptosis. Proteomic and metabolomic analyses identifies branched-chain amino acid (BCAA) metabolism as a key downstream pathway regulated by SIRT5 through branched-chain aminotransferase 1 (BCAT1). Specifically, SIRT5-mediated desuccinylation of BCAT1 at K39 inhibits its interaction with the E3 ligase CHIP, thereby preventing BCAT1 degradation via the ubiquitin-proteasome system. Moreover, BCAT1 overexpression reverses the proliferation inhibition and ferroptosis sensitivity observed in SIRT5-knockdown cells. Clinically, we reveal a positive correlation between SIRT5 and BCAT1 levels in glioma samples, with higher expression levels predicting more advanced glioma grades and poorer clinical outcomes. Collectively, this study highlights the critical role of SIRT5 in promoting glioma progression via metabolic regulation and ferroptosis insensitivity, offering a potential therapeutic target for glioma treatment.

OBJECTIVE:The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). METHODS:92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. RESULTS:the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). CONCLUSION:SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.

Background: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. Methods: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index. The GSVA and GSEA were performed to explore functional annotations. The CIBERSORT and ESTIMATE algorithms were utilized to investigate the immune infiltration status of the two groups. Additionally, we utilized the Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenotype Score (IPS), and pRRophetic algorithms to predict the effectiveness of different treatment modalities. Results: We constructed a radiosensitivity index consists of four DNA repair-related genes. Patients in the RS group demonstrated significantly improved prognosis compared to patients in the RR group when treated with radiotherapy. We observed that the RS group exhibited a higher proportion of the POLE ultra-mutated subtype, while the RR group had a higher proportion of the copy number high subtype. GSVA enrichment analysis revealed that the RS group exhibited enrichment in DNA damage repair pathways. Notably, the RS group demonstrated a higher proportion of naïve B cells and follicular helper T cells, while regulatory T cells (Tregs) and memory B cells were more abundant in the RR group. Furthermore, patients in the RS-PD-L1-high subgroup exhibited enrichment in immune-related pathways and increased sensitivity to immunotherapy, which is likely to contribute to their improved prognosis. Additionally, we conducted in vitro experiments to validate the expression of radiosensitivity genes in non-radioresistant (AN3CA) and radioresistant (AN3CA/IR) endometrial cancer cells. Conclusions: In conclusion, our research successfully constructed a radiosensitivity signature with robust predictive capacity. These findings shed light on the association between immune activation, PD-L1 expression, and the response to immunotherapy in the context of radiotherapy.

BackgroundTongue squamous cell carcinoma (TSCC) is a prevalent tumor that affects many people worldwide. Radiotherapy is a common treatment option, but its efficacy varies greatly. This study seeks to validate the identified gene signature associated with radiosensitivity in TSCC, and its potential in predicting radiotherapy response and prognosis.MethodsWe analyzed 122 TSCC patients from TCGA database using the radiosensitivity signature and classified them into radiosensitive (RS) and radioresistant (RR) groups. Immune infiltration analysis methods were applied to investigate the immune status between different subgroups. Immunophenotype Score (IPS) and pRRophetic algorithm were employed to estimate the efficiency of treatment. A radioresistant TSCC cell line was established by gradually increasing radiation doses. Cell radiosensitivity was evaluated using the CCK-8 and colony formation assays. The expression of radiosensitivity-related genes was validated by qRT-PCR.ResultsOur study validated the predictive capacity of a previously identified “31-gene signature” in the TCGA-TSCC cohort, which effectively stratified patients into RS and RR groups. We observed that the RS group exhibited superior overall survival and progression-free survival rates relative to the RR group when treated with radiotherapy. The RS group was significantly enriched in most immune-related hallmark pathways, and may therefore benefit from immune checkpoint inhibitors. However, the RS group displayed lower sensitivity to first-line chemotherapy. A radioresistant TSCC cell line (CAL-27R) exhibited increased clonogenic potential and cell viability following irradiation, accompanied by downregulation of three radiosensitivity-related genes compared to its parental non-resistant cell (CAL-27). In addition, we constructed and validated a radiosensitivity-related prognostic index (PI) using 4 radiosensitivity-related genes associated with TSCC prognosis.ConclusionWe assessed the ability of the radiosensitivity gene signature to predict outcomes in TSCC patients. our research provided valuable insights into the molecular pathways associated with radiosensitivity in TSCC and offered clinicians a practical tool to predict patient radiotherapy effectiveness and prognosis.

133 Background: To calculate the percentage of tumor-infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) using deep-learning (DL) algorithms based on digital pathology images and differentiate the outcome. Methods: We recruited 435 patients with primary non-metastatic NPC and 63 patients with de novo metastatic NPC received immunotherapy. TILDL percentage was calculated using the convolutional neural network model, and its ability to differentiate metastasis risk and independent prognostic value were analyzed using Kaplan–Meier survival and multivariate analyses (MVA). Results: The median follow-up time of the training and validation cohorts was 69, and 76 months, respectively. Kaplan–Meier survival analysis showed that the 5-year distant metastasis-free survival (DMFS) and overall survival (OS) of patients with high TILDL were significantly better than those of patients with low infiltration. MVA showed that TILDL degree is an independent prognostic factor for DMFS (training cohort: HR=0.197, 95% CI: 0.077-0.503, p=0.001; validation cohort: HR=0.119, 95% CI: 0.028-0.503, p=0.004) and OS (training cohort: HR=0.418, 95% CI: 0.200-0.873, p=0.020; validation cohort: HR=0.158, 95% CI: 0.048-0.520, p=0.002). The concordance index (C-index) of TILDL was higher than that of the immunohistochemical CD3+, CD8+ T-cell, and CD20+ B-cell densities in terms of the DMFS and OS prediction accuracy. In an immunotherapy cohort of de novo metastatic NPC (n=63), MAV revealed that high TILDL percentage were an independent prognostic factor for PFS (HR=0.368, p= 0.008). Conclusions: TILDL percentage exhibited discriminative capabilities regarding the risk of metastasis and mortality in non-metastatic NPC, and has potential to be a biomarker for dmNPC received immunotherapy. This model will help select patients with a high risk of metastasis and provides a reference for improved individualized treatment.

Thyroid cancer (TC) is a very common endocrine cancer worldwide. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. Long non-coding RNAs (lncRNAs), a series of non-coding RNAs with a length of >200 nts, have been regarded as crucial regulators of many cancers playing a tumor suppressive or oncogenic role, depending on circumstances. lncRNA ZNF674-AS1 was reported to be abnormally expressed in TC, but the exact mechanism remains unclear. This study aims to probe the mechanism and roles of ZNF674-AS1 in TC. The expression patterns of RNAs and proteins were determined via qRT-PCR and western blotting, respectively. Cell proliferation, migration and invasion were detected using MTT and Transwell assays. ZNF674-AS1 and SOCS4 expression were remarkably reduced while miR-181a was upregulated in TC tissues and cells. Enforced expression of ZNF674-AS1 inhibited proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and reduced tumour growth in vivo. Mechanistic assays verified that ZNF674-AS1 directly interacted with miR-181a to increase SOCS4 expression. In addition, miR-181a overexpression aggravated proliferation, metastasis and EMT by inhibiting SOCS4. Interestingly, inhibition of miR-181a diminished the promoting effects of ZNF674-AS1 silencing on the malignant behaviours of TC cells. These data illustrated that ZNF674-AS1 alleviated TC progression by modulating the miR-181a/SOCS4 axis (graphical abstract), further suggesting that ZNF674-AS1 might be used as a therapheutic target in TC treatment.

Ethnopharmacological relevance: Gypenosides (Gyp), Chinese medicine and an effective ingredient extracted from Gynostemma pentaphyllum , have important effects on the progression of various cancers. However, their biological functions in glioma and mechanisms remain unclear.Aim of the study: In this study, we tried to investigate the gypenosides and potential mechanisms in Glioma treatment through network pharmacology and in vitro experiments.Material/methods: Cell viability was tested using MTS assays and cell mobility was evaluated using Transwell invasion and scratch migration assays with human glioma cells. Additionally, we assessed apoptosis using flow cytometry and Hoechst 33342 staining, while autophagy flow was detected using fluorescence microscopy. Moreover, the levels of migration-, apoptosis-, and autophagy-related proteins were examined using western blotting.Results: Gyp inhibited the proliferation, migration, and invasion of glioma cells by downregulating the levels of matrix metalloproteinase MMP-2 and MMP-9. Moreover, they promoted glioma cell apoptosis by inducing Bax and cleaved-caspase-9 activation and downregulating Bcl-2 expression. Notably, autophagy was activated by treating U251 and U87 cells with Gyp through the downregulation of p62 protein expression and upregulation of Beclin1 and LC3 II protein expression. Interestingly, treatment with the autophagy flux inhibitors Baf-A1 or 3-MA blocked Gyp-induced autophagy in glioma cells. Further, the combined application of Gyp with Baf-A1 or 3-MA slightly increased cell death, suggesting that autophagy induction impaired enzyme accumulation and contributed to the inhibition of glioma cell growth.Conclusions: Gypenosides inhibit glioma growth by regulating apoptosis and autophagy, suggesting their potential value for the combined treatment of glioma.

Abstract Gypenosides (Gyp), a Chinese medicine and an effective ingredient extracted from Gynostemma pentaphyllum, plays vital roles in the progression of various cancers. However, its biological functions and mechanisms in glioma remain unclear. We evaluated the anti-cancer mechanism of Gyp in glioma to determine its potential therapeutic value. In human glioma cells, we evaluated cell viability using MTS assays and cell mobility using Transwell invasion and scratch migration assays. Additionally, we assessed apoptosis using flow cytometry and Hoechst 33342 staining, and autophagy flow was detected by Fluorescence microscope. The levels of migration, apoptosis and autophagy-related protein were examinated by Western blot. Gyp inhibited the proliferation, migration and invasion of glioma cells by down-regulating the level of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, Gyp promoted apoptosis of glioma cells by inducing Bax and cleaved-caspase-9 activation and down-regulating Bcl-2. Notably, autophagy was activated by treating with Gyp in U251 and U87 cells through down-regulation of p62 protein and up-regulation of Beclin1 and LC3 II proteins. Interestingly, treatment with autophagy flux inhibitor Baf-A1 or 3-MA blocked the inhibitory effects of Gyp in glioma cells. Combined application of Gyp with Baf-A1 or 3-MA slightly increased cell death, suggesting that induction of autophagy impaired enzyme accumulation and contributed to the growth inhibition of glioma cells. In summary, Gyp suppressed the proliferation, migration and invasion and induced apoptosis of glioma cells by promoting autophagy, suggested the potential value of Gyp in the combined treatment of glioma.

As a member of integrin receptor family, ITGAV (integrin subunit α V) is involved in a variety of cell biological processes and overexpressed in various cancers, which may be a potential prognostic factor. However, its prognostic value and potential function in lower-grade glioma (LGG) are still unclear, and in terms of immune infiltration, it has not been fully elucidated. Here, the expression preference, prognostic value, and clinical traits of ITGAV were investigated using The Cancer Genome Atlas database (n = 528) and the Chinese Glioma Genome Atlas dataset (n = 458). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA) were used to explore the biological function of ITGAV. Using R package “ssGSEA” analysis, it was found thatthe ITGAV mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and multiple immune-related genes. In addition, ITGAV is associated with some immune checkpoints and immune checkpoint blockade (ICB) and response to chemotherapy. and the expression of ITGAV protein in LGG patients was verified via immunohistochemistry (IHC). ITGAV expression was higher in LGG tissues than in normal tissues (P < 0.001) and multifactor analysis showed that ITGAV mRNA expression was an independent prognostic factor for LGG overall survival (OS; hazard ratio = 2.113, 95% confidence interval = 1.393–3.204, P < 0.001). GSEA showed that ITGAV expression was correlated with Inflammatory response, complement response, KRAS signal, and interferon response. ssGSEA results showed a positive correlation between ITGAV expression and Th2 cell infiltration level. ITGAV mRNA was overexpressed in LGG, and high ITGAV mRNA levels were found to be associated with poor protein expression and poor OS. ITGAV is therefore a potential biomarker for the diagnosis and prognosis of LGG and may be a potential immunotherapy target.

This study aimed to construct a signature of N6-methyladenosine (m6A) regulator-related genes that could be used for the prognosis of head and neck squamous cell carcinoma (HNSCC) and to clarify the molecular and immune characteristics and benefits of immune checkpoint inhibitor (ICI) therapy using the prognostic signature to define the subgroups of HNSCC. This study showed that eighteen m6A regulators were abnormally expressed in the Cancer Genome Atlas (TCGA) HNSCC tissues compared with those in normal tissues. We constructed a signature of 12 m6A regulator-related genes using the Cox risk model, combined with the least absolute shrinkage and selection operator (Lasso) variable screening algorithm. Based on the median of the signature risk score, the patients were divided into high- and low-risk groups. The Kaplan–Meier survival analyses showed that patients with high-risk scores demonstrated poorer overall survival (OS) than those with low-risk scores based on TCGA-HNSCC data (p <0.001). The OS of high-risk patients was significantly worse than that of low-risk patients in the GSE65858 (p <0.001) and International Cancer Genome Consortium (ICGC) oral cancer cohorts (p = 0.0089). Furthermore, immune infiltration analyses showed that 8 types of immune cell infiltration showed highly significant differences between the two risk groups (p <0.001). In the Imvigor210CoreBiologies dataset of patients who received ICIs, the objective response rate (ORR) of the low-risk group (32%) was significantly higher than that of the high-risk group (13%). Additionally, patients in the high-risk group presented with a more significant adverse OS than that of the low-risk group (p = 0.00032). GSE78220 also showed that the ORR of the low-risk group (64%) was higher than that of the high-risk group (43%) and the OS of low-risk patients was better than that of high-risk patients (p = 0.0064). The constructed prognostic signature, based on m6A regulator-related genes, could be used to effectively distinguish between prognoses for HNSCC patients. The prognostic signature was found to be related to the immune cell infiltration of HNSCC; it might help predict the responses and prognoses of ICIs during treatment.

Abstract Background: Glioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis.Methods: Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan–Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively.Results: We detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p = 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines.Conclusions: We established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.

Background: Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR. Results: HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue ( p < 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169–2.266, p = 0.004) and GSE41613 data (HR = 2.238, p = 0.013). The methylation level of HMMR negatively correlated with the HMMR expression ( R = −0.12, p < 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation ( p < 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed that HMMR expression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288, p = 0.045) and progression-free survival (HR = 2.247, p = 0.038) in 70 HNSCC. Conclusions: This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.

Background: Glioma is the most common primary tumor of the central nervous system and is associated with poor overall survival, creating an urgent need to identify survival-associated biomarkers. C1ORF112, an alpha-helical protein, is overexpressed in some cancers; however, its prognostic role has not yet been explored in gliomas. Thus, in this study, we attempted to address this by determining the prognostic value and potential function of C1ORF112 in low-grade gliomas (LGGs). Methods: The expression of C1ORF112 in normal and tumor tissues was analyzed using data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Oncomine, and Rembrandt databases. The genetic changes of C1ORF112 in LGG were analyzed using cBioPortal. Survival analysis was used to evaluate the relationship between C1ORF112 expression and survival in patients with LGG. Correlation between immune infiltration and C1ORF112 expression was determined using Timer software. Additionally, data from three online platforms were integrated to identify the co-expressed genes of C1ORF112. The potential biological functions of C1ORF112 were investigated by enrichment analysis. Results: C1ORF112 mRNA was highly expressed in LGGs (p < 0.01). Area under the ROC curve (AUC) showed that the expression of C1ORF112 in LGG was 0.673 (95% confidence interval [CI] = 0.618–0.728). Kaplan-Meier survival analysis showed that patients with high C1ORF112 expression had lower OS than patients with low C1ORF112 expression (p < 0.05). Multivariate analysis showed that high expression of C1ORF112 was an independent prognostic factor for the overall survival in patients from TCGA and CGGA databases. C1ORF112 expression was positively correlated with six immunoinfiltrating cells (all p < 0.001). The enrichment analysis suggested the enrichment of C1ORF112 and co-expressed genes in cell cycle and DNA replication. Conclusion: This study suggested that C1ORF112 may be a prognostic biomarker and a potential immunotherapeutic target for LGG.

Glioblastoma multiforme (GBM) is the most malignant glioma with a high death rate. N6-methyladenosine (m6A) RNA methylation plays an increasingly important role in tumors. The current study aimed to determine the function of the regulators of m6A RNA methylation in GBM. We evaluated the difference, interaction, and correlation of these regulators with TCGA database. HNRNPC, WTAP, YTHDF2 and, YTHDF1 were significantly upregulated in GBM. To explore the expression characteristics of regulators in GBM, we defined two subgroups through consensus cluster. HNRNPC, WTAP, and YTHDF2 were significantly upregulated in the cluster2 which had a good overall survival (OS). To investigate the prognostic value of regulators, we used lasso cox regression algorithm to screen an independent prognostic risk characteristic based on the expression of HNRNPC, ZC3H13, and YTHDF2. The prognostic feature between the low and high-risk groups was significantly different (P < 0.05), which could predict significance of prognosis (area under the curve (AUC) = 0.819). Moreover, we used western blot, RT-PCR, and immunohistochemical staining to verify the expression of HNRNPC was associated with malignancy and development of gliomas. Similarly, the high expression of HNRNPC had a good prognosis. In conclusion, HNRNPC is a vital participant in the malignant progression of GBM and might be valuable for prognosis.