Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial.

PURPOSE: The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier utilizing plasma metabolomics profiling. EXPERIMENTAL DESIGN: A total of 166 NPC patients enrolled in the clinical trial NCT05682703 and undergoing IC were included in the study. Plasma lipoprotein profiles were obtained using 1H-NMR before and after IC treatment. An AI-assisted radiomics method was developed to effectively evaluate the efficacy. Metabolic biomarkers were identified through a machine learning approach based on a discovery cohort and subsequently validated in a validation cohort that mimicked the most unfavorable scenario in real-world. RESULTS: Our research findings indicate that the effectiveness of IC varies among individual patients, with a correlation observed between efficacy and changes in metabolite profiles. Utilizing machine learning techniques, it was determined that the XGB model exhibited notable efficacy, attaining an Area Under the Curve (AUC) value of 0.792 (95% CI, 0.668-0.913). In the validation cohort, the model exhibited strong stability and generalizability with an AUC of 0.786 (95%CI, 0.533-0.922). CONCLUSION: In this study, we found that dysregulation of plasma lipoprotein may result in resistance to IC in NPC patients. The prediction model constructed based on the plasma metabolites' profile as good predictive capabilities and potential for real-world generalization. This discovery has implications for the development of treatment strategies and may offer insight into potential targets for enhancing the effectiveness of IC.

The development of a novel zeolite-based assay for efficient and deep plasma proteomic profiling.

Plasma proteins are considered the most informative source of biomarkers for disease diagnosis and monitoring. Mass spectrometry (MS)-based proteomics has been applied to identify biomarkers in plasma, but the complexity of the plasma proteome and the extremely large dynamic range of protein abundances in plasma make the clinical application of plasma proteomics highly challenging. We designed and synthesized zeolite-based nanoparticles to deplete high-abundance plasma proteins. The resulting novel plasma proteomic assay can measure approximately 3000 plasma proteins in a 45 min chromatographic gradient. Compared to those in neat and depleted plasma, the plasma proteins identified by our assay exhibited distinct biological profiles, as validated in several public datasets. A pilot investigation of the proteomic profile of a hepatocellular carcinoma (HCC) cohort identified 15 promising protein features, highlighting the diagnostic value of the plasma proteome in distinguishing individuals with and without HCC. Furthermore, this assay can be easily integrated with all current downstream protein profiling methods and potentially extended to other biofluids. In conclusion, we established a robust and efficient plasma proteomic assay with unprecedented identification depth, paving the way for the translation of plasma proteomics into clinical applications.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

Exploring prognostic value and regulation network of PPP1R1A in hepatocellular carcinoma.

Novel and accurate biomarkers are needed for early detection and progression evaluation of hepatocellular carcinoma (HCC). Protein phosphatase 1 regulatory subunit 1A (PPP1R1A) has been studied in cancer biology; however, the expression pattern and biological function of PPP1R1A in HCC are unclear. The differentially expressed genes (DEGs) in HCC were screened by The Cancer Genome Atlas (TCGA) database. Real-time PCR and immunohistochemistry (IHC) assay were used to detect the expression of PPP1R1A in BALB/c mice, human normal tissues and corresponding tumor tissues, especially HCC. Then, Kaplan-Meier analysis of patients with HCC was performed to evaluate the relationship between PPP1R1A expression and prognosis. The transcriptional regulatory network of PPP1R1A was constructed based on the differentially expressed mRNAs, microRNAs and transcription factors (TFs). To explore the downstream regulation of PPP1R1A, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and immune infiltration score were performed. A total of 4 DEGs were screened out. PPP1R1A was differentially distributed and expressed in BALB/c mice and human tissues. PPP1R1A expression was higher in normal tissues than that in tumor tissues, and patients with higher PPP1R1A expression had better clinical outcome in HCC. In addition, we constructed miR-21-3p/TAL1/PPP1R1A transcriptional network. Furthermore, PPP1R1A may modulate the activation of PI3K-Akt pathway, cell cycle, glycogen metabolism and the recruitment of M2 macrophage in HCC. This study may help to clarify the function and mechanism of PPP1R1A in HCC and provide a potential biomarker for tumor prevention and treatment.

Evaluation of the TRIP13 level in breast cancer and insights into potential molecular pathways.

TRIP13 is a member of the large superfamily of the AAA + ATPase proteins and is associated with a variety of activities. Emerging evidence has shown that TRIP13 may serve as an oncogene. However, the function of TRIP13 in breast cancer (BC) has not yet been elucidated. Here, a variety of bioinformatic tools and laboratory experiments were combined to analyse the expression patterns, prognostic value and functional network of TRIP13 in BC. Multiple databases and immunohistochemistry (IHC) indicated a higher TRIP13 expression in BC tissue compared with normal tissue. TRIP13 was highly expressed in lung metastatic lesions compared with primary tumours in a 4T1 cell implantation BALB/c mouse model of BC. Kaplan-Meier plots also revealed that high TRIP13 expression correlated with poor survival in patients with BC. Furthermore, gene set enrichment analysis revealed that TRIP13 was primarily enriched in the signalling pathway of PI3K-AKT-mTOR. Suppressing TRIP13 could inhibit the expression of related genes, as well as the proliferation and migration of BC cell. Finally, 10 hub genes with a high score of connectivity were filtered from the protein-protein interaction (PPI) network, including MAD2L1, CDC20, CDC5L, CDK1, CCNA2, BUB1B, RAD51, SPO11, KIF11 and AURKB. Thus, TRIP13 may be a promising prognostic biomarker and an effective therapeutic target for BC.

COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma.

BACKGROUND & AIMS: Copper (Cu) is an essential trace element whose serum levels have been reported to act as an effective indicator of the efficacy of radiotherapy. However, little is known about the role of Cu in radiotherapy. In this study we aimed to determine this role and investigate the precise mechanism by which Cu or Cu-related proteins regulate the radiosensitivity of hepatocellular carcinoma (HCC). METHODS: The expression and function of Cu and copper metabolism MURR1 domain 10 (COMMD10) were assessed via a Cu detection assay, immunostaining, real-time PCR, western blot, a radiation clonogenic assay and a 5-ethynyl-2'-deoxyuridine assay. Ferroptosis was determined by detecting glutathione, lipid peroxidation, malondialdehyde and ferrous ion (Fe) levels. The in vivo effects of Cu and COMMD10 were examined with Cu/Cu chelator treatment or lentivirus modification of COMMD10 expression in radiated mouse models. RESULTS: We identified a novel role of Cu in promoting the radioresistance of HCC cells. Ionizing radiation (IR) induced a reduction of COMMD10, which increased intracellular Cu and led to radioresistance of HCC. COMMD10 enhanced ferroptosis and radiosensitivity in vitro and in vivo. Mechanistically, low expression of COMMD10 induced by IR inhibited the ubiquitin degradation of HIF1α (by inducing Cu accumulation) and simultaneously impaired its combination with HIF1α, promoting HIF1α nuclear translocation and the transcription of ceruloplasmin (CP) and SLC7A11, which jointly inhibited ferroptosis in HCC cells. In addition, elevated CP promoted HIF1α expression by reducing Fe, forming a positive feedback loop. CONCLUSIONS: COMMD10 inhibits the HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe homeostasis in HCC. This work provides new targets and treatment strategies for overcoming radioresistance in HCC. LAY SUMMARY: Radiotherapy benefits patients with unresectable or advanced hepatocellular carcinoma (HCC), but its effectiveness is hampered by radioresistance. Herein, we uncovered a novel role for copper in promoting the radioresistance of HCCs. This work has revealed new targets and potential treatment strategies that could be used to sensitize HCC to radiotherapy.

SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma.

Pulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

COMMD10 inhibits tumor progression and induces apoptosis by blocking NF-κB signal and values up BCLC staging in predicting overall survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Currently, there is limited knowledge of dysregulation of cellular proliferation and apoptosis that contribute to the malignant phenotype in HCC. Copper metabolism gene MURR1 domain 10 (COMMD10) is initially identified as a suppressor gene in the pathogenesis of HCC in our observations. Here we aimed to explore its function and prognostic value in the progression of HCC. METHODS: Functional experiments were performed to explore the role of COMMD10 in HCC. The molecular mechanisms of COMMD10 were determined by luciferase assay, immunofluorescence, and immunoprecipitation. The nomogram was based on a retrospective and multicenter study of 516 patients who were pathologically diagnosed with HCC from three Chinese hospitals. The predictive accuracy and discriminative ability of the nomogram were determined by a C-index and calibration curve and were compared with COMMD10 and the Barcelona Clinic Liver Cancer (BCLC) staging system. The primary endpoint was overall survival (OS). RESULTS: COMMD10 expression was significantly lower in HCC than that in normal liver tissues. In vitro and in vivo experiments revealed that COMMD10 suppressed cell proliferation and induced apoptosis in HCC. Mechanistically, COMMD10 inhibits TNFα mediated ubiquitination of IκBα and p65 nuclear translocation through the combination of COMMD10-N terminal to the Rel homology domain of p65, which inhibited NF-κB activity and increased expression of cleaved caspase9/3 in HCC. Clinically, COMMD10 stratifies early-stage HCC patients into two risk groups with significantly different OS. Additionally, the nomogram based on COMMD10 and BCLC stage yielded more accuracy than BCLC stage alone for predicting OS of HCC patients in three cohorts. CONCLUSIONS: COMMD10 suppresses proliferation and promotes apoptosis by inhibiting NF-κB signaling and values up BCLC staging in predicting OS, which provides evidence for the identification of potential therapeutic targets and the accurate prediction of prognosis for patients with HCC.

Cancer-associated fibroblasts promote the survival of irradiated nasopharyngeal carcinoma cells via the NF-κB pathway.

BACKGROUND: Irradiation has emerged as a valid tool for nasopharyngeal carcinoma (NPC) in situ treatment; however, NPC derived from tissues treated with irradiation is a main cause cancer-related death. The purpose of this study is to uncover the underlying mechanism regarding tumor growth after irradiation and provided potential therapeutic strategy. METHODS: Fibroblasts were extracted from fresh NPC tissue and normal nasopharyngeal mucosa. Immunohistochemistry was conducted to measure the expression of α-SMA and FAP. Cytokines were detected by protein array chip and identified by real-time PCR. CCK-8 assay was used to detect cell proliferation. Radiation-resistant (IRR) 5-8F cell line was established and colony assay was performed to evaluate tumor cell growth after irradiation. Signaling pathways were acquired via gene set enrichment analysis (GSEA). Comet assay and γ-H2AX foci assay were used to measure DNA damage level. Protein expression was detected by western blot assay. In vivo experiment was performed subcutaneously. RESULTS: We found that radiation-resistant NPC tissues were constantly infiltrated with a greater number of cancer-associated fibroblasts (CAFs) compared to radiosensitive NPC tissues. Further research revealed that CAFs induced the formation of radioresistance and promoted NPC cell survival following irradiation via the IL-8/NF-κB pathway to reduce irradiation-induced DNA damage. Treatment with Tranilast, a CAF inhibitor, restricted the survival of CAF-induced NPC cells and attenuated the of radioresistance properties. CONCLUSIONS: Together, these data demonstrate that CAFs can promote the survival of irradiated NPC cells via the NF-κB pathway and induce radioresistance that can be interrupted by Tranilast, suggesting the potential value of Tranilast in sensitizing NPC cells to irradiation.

Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors.

Carbohydrate sulfotransferase 4 (CHST4) plays an important role in lymphocyte homing and is abnormally expressed in several cancer types; however, its precise function in tumor development and progression is unknown. Here we confirm that CHST4 is aberrantly expressed in various tumor subtypes. In particular, we found that CHST4 expression was downregulated in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) tumors compared to paired normal tissue. We also showed that CHST4 overexpression inhibited the proliferation and metastasis of HCC cells in vitro. Clinically, CHST4 was identified as an independent prognostic factor for HBV-HCC patients. We further illuminated the anti-tumor role and mechanism of CHST4 in HBV-HCC by constructing a FENDRR-miR-10b-5p-CHST4 competing endogenous RNA network. We found that downregulation of CHST4 expression may promote HBV expression and regulate ribonucleoprotein complex biogenesis to promote malignant behaviors in HBV-HCC. CHST4 may also recruit CD4+ T cells, macrophages, dendritic cells, and neutrophils into the tumor microenvironment to inhibit the progression of HBV-HCC. Overall, our findings suggest that CHST4 acts as a tumor suppressor in HCC-HBV and represents a potential diagnostic and therapeutic target.

Interferon-Induced Protein 44 Correlated With Immune Infiltration Serves as a Potential Prognostic Indicator in Head and Neck Squamous Cell Carcinoma.

Interferon-induced protein 44 (IFI44) containing a guanosine-5'-triphosphate (GTP) binding domain was reported to play a significant role in the immune response to autoimmune disease. However, its roles involved in cancers remain unclear. Here, we detected the expression of IFI44 in The Cancer Genome Atlas (TCGA) Pan-cancer and generally explored the effect of IFI44 on immune infiltration in the tumor microenvironment (TME). The results displayed that IFI44 was mainly located in the cytoplasm and overexpressed in head and neck squamous cell carcinoma (HNSC) samples compared with normal tissues. Survival analysis exhibited that IFI44 was remarkably associated with the clinical outcomes, particularly in lymph node-positive and locally advanced HNSC patients. Biological analysis showed that IFI44 was correlated with such immune biological processes as antigen-presenting and nuclear factor (NF)-kappa B signaling pathways. Immune signature analysis demonstrated that the expression of IFI44 was positively correlated with the infiltration of CD4+ cells and macrophages as well as neutrophils in HNSC. Taken together, these data suggested that IFI44 was abnormally expressed in cancer tissues and indicated the potential impact of IFI44 on the tumor immune infiltration in HNSC.

Expression profile of SYNE3 and bioinformatic analysis of its prognostic value and functions in tumors.

BACKGROUND: Spectrin repeat containing nuclear envelope family member 3 (SYNE3) encodes an essential component of the linker of the cytoskeleton and nucleoskeleton (LINC) complex, namely nesprin-3. In a tumor, invasiveness and metastasis rely on the integrity of the LINC complex, while the role of SYNE3/nesprin-3 in cancer is rarely studied. METHODS: Here, we explored the expression pattern, prognostic value, and related mechanisms of SYNE3 through both experimental and bioinformatic methods. We first detected SYNE3 in BALB/c mice, normal human tissues, and the paired tumor tissues, then used bioinformatics databases to verify our results. We further analyzed the prognostic value of SYNE3. Next, we predicted miRNA targeting SYNE3 and built a competing endogenous RNA (ceRNA) network and a transcriptional network by analyzing data from the cancer genome atlas (TCGA) database. Interacting genes of SYNE3 were predicted, and we further performed GO and KEGG enrichment analysis on these genes. Besides, the relationship between SYNE3 and immune infiltration was also investigated. RESULTS: SYNE3 exhibited various expressions in different tissues, mainly located on nuclear and in cytoplasm sometimes. SYNE3 expression level had prognostic value in tumors, possibly by stabilizing nucleus, promoting tumor cells apoptosis, and altering tumor microenvironment. Additionally, we constructed a RP11-2B6.2-miR-149-5p-/RP11-67L2.2-miR-330-3p-SYNE3 ceRNA network and a SATB1-miR-149-5p-SYNE3 transcriptional network in lung adenocarcinoma to support the tumor-suppressing role of SYNE3. CONCLUSIONS: Our study explored novel anti-tumor functions and mechanisms of SYNE3, which might be useful for future cancer therapy.

CLIC4 regulates radioresistance of nasopharyngeal carcinoma by iNOS after γ-rays but not carbon ions irradiation.

Nasopharyngeal carcinoma (NPC) is a major health problem in the East and Southeast Asia, and the intensity modulated radiotherapy (IMRT) is the current preferred treatment method of NPC, but radioresistance-induced residual and recurrent tumors are the main cause of treatment failure. Till now, the mechanism of radioresistance and prognostic biomarkers of NPC are still unrevealed. In this study, we collected clinical NPC samples and established radioresistant NPC-R cell lines by irradiating NPC cells with fractionation doses of γ-rays. Using genechip assay between radioresistance and radiosensitive clinical samples and TMT assay between NPC and NPC-R cells, differential expressed genes were examined and the potential biomarker of radioresistance was screened. Immunohistochemical assay of NPC clinical specimens showed that CLIC4 was significantly up-regulated in radioresistance tumor tissues. In vitro studies confirmed that up-regulation of CLIC4 gene enhanced radioresistance in comparison with the alterations of intracellular oxidative metabolism of reactive oxygen species (ROS) and nitric oxide (NO) in an opposite way. Correspondingly, inhibition of CLIC4 sensitized NPC cells to irradiation and decreased nuclear translocation of iNOS and intracellular level of NO in NPC cells. Interestingly, the capacity for DNA repair had no difference between NPC and NPC-R cells. Moreover, because of great interests in using carbon ion irradiation to treat NPC effectively, we demonstrated that, after carbon ion irradiation, NPC-R and NPC cells had similar survival even under the status of up- or down-regulation of CLIC4. Conclusively, CLIC4 contributes to radioresistance of NPC to γ-rays but not carbon ions by regulating intracellular oxidative metabolism of nuclear translocation of iNOS.

Expression profile and bioinformatics analysis of COMMD10 in BALB/C mice and human.

COMMD10, a member of COMMD protein, has been proved to target p65 NF-kappaB (nuclear factor-kappaB) subunit and reduce its nuclear translocation, thereby leading to the inactivation of NF-kappaB pathway and suppression of colorectal cancer invasion and metastasis. The aim of this study is to explore its expression pattern and tissue distribution in human normal tissues and other tumor tissues and to investigate the relevant mechanism. We firstly provided the expression profile and histological distribution of COMMD10 in various BALB/c mice tissues and identified the biological distribution of COMMD10 in different kinds of human normal and tumor tissues. We verified the expression profile of COMMD10 using TCGA database. The interacting genes of COMMD10 were predicted by using STRING using. Finally, we performed database, and the microRNAs targeting COMMD10 were predicted using miRDB, miRWalk, TargetScan and microRNA. GO and KEGG pathway analyses were performed to predict the biological function of COMMD10 and its interacting genes. mRNA expression of COMMD10 showed the highest level in the lung and spleen, and the lowest level in the heart and brain. Immunohistochemistry detection revealed that COMMD10 was expressed in different tissues with different degrees and was was located mainly in the cytoplasm. Subsequently, we showed that COMMD10 displayed various degrees of expression in different human normal tissues that mainly located in cytoplasm, while COMMD10 of liver cells resided in both nucleus and cytoplasm. All the tumor tissues except breast small cell carcinoma, breast phyllodes tumor, lung adenocarcinoma, thymoma, cervical cancer and bladder urothelial carcinoma showed that COMMD10 was positive staining in cytoplasm. Kaplan-Meier plotter indicated that renal clear cell carcinoma patients with increased expression level of COMMD10 exhibited longer survival. STRING database revealed that COMMD10 had 41 interacting genes, and data from 4 different databases indicated that hsa-miR-590-3p may be the potential regulator of COMMD10. GO analysis demonstrated that COMMD10 and its interacting genes were mainly enriched in Cullin-RING ubiquitin ligase complexes, binding and transport of copper ions, the transport and steady-state maintenance of copper ions, transcription, translation and transport of proteins, and negatively regulate the activity of NF-kappaB transcription factors. KEGG pathway showed that COMMD10 and its interacting genes were mainly involved in renal cell carcinoma, HIF-1 signaling pathways, ubiquitination-mediated proteolysis, endocytosis and mineral absorption. COMMD10 may play a tumor suppressive role in renal clear cell carcinoma through the miR-590-3p-COMMD10-Cul2-RBX1-NF-κB/HIF/NRF2 pathway and regulate the chemotherapy resistance of various tumor cells to cisplatin.

Prognosis and modulation mechanisms of COMMD6 in human tumours based on expression profiling and comprehensive bioinformatics analysis.

BACKGROUND: The Copper Metabolism MURR1 (COMM) domain family has been reported to play important roles in tumorigenesis. As a prototype for the COMMD family, the expression pattern and biological function of COMMD6 in human tumours remain unknown. METHODS: COMMD6 expression in BALB/c mice and human tissues was examined using real-time PCR and immunohistochemistry. Kaplan-Meier analysis was applied to evaluate the prognosis of COMMD6 in tumours. Competing endogenous RNA (ceRNA) and transcriptional regulation network were constructed based on differentially expressed mRNAs, microRNAs and long non-coding RNAs from the cancer genome atlas database. GO and KEGG enrichment analysis were used to explore the bioinformatics implication. RESULTS: COMMD6 expression was widely observed in BALB/c mice and human tissues, which predicted prognosis of cancer patients. Furthermore, we shed light on the underlying tumour promoting role and mechanism of COMMD6 by constructing a TEX41-miR-340-COMMD6 ceRNA network in head and neck squamous cell carcinoma and miR-218-CDX1-COMMD6 transcriptional network in cholangiocarcinoma. In addition, COMMD6 may modulate the ubiquitination and degradation of NF-κB subunits and regulate ribonucleoprotein and spliceosome complex biogenesis in tumours. CONCLUSIONS: This study may help to elucidate the functions and mechanisms of COMMD6 in human tumours, providing a potential biomarker for tumour prevention and therapy.