HOXB7 induces STAT3-mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells.

The homeobox family genes are often dysregulated in various cancer types. Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anticancer drug resistance, and angiogenesis. In this study, we show that HOXB7 is coamplified with ERBB2 in a subset of breast cancer patients and HOXB7 expression correlates with poor prognosis in HER2-positive breast cancer patients. This clinical observation is supported by the following results-HOXB7 overexpression in an immortalized murine mammary gland epithelial cell line NMuMG induces cellular transformation in vitro, tumorigenesis, and lung metastasis through the activation of JAK-STAT signaling.

Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.

BACKGROUND: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation. METHODS: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers. RESULTS: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs. CONCLUSION: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.

Mitogen-activated protein kinase inhibition augments the T cell response against HOXB7-expressing tumor through human leukocyte antigen upregulation.

Homeobox B7 (HOXB7) is a master regulatory gene that regulates cell proliferation and activates oncogenic pathways. Overexpression of HOXB7 correlates with aggressive behavior and poor prognosis in patients with cancer. However, the expression and role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we observed that most samples from patients with oropharyngeal cancer and HNSCC expressed HOXB7. As no direct inhibitor has been reported, we identified a potent peptide epitope to target HOXB7-expressing tumors through immune cells. A novel HOXB7-derived peptide epitope (HOXB78-25 ) elicited antigen-specific and tumor-reactive promiscuous CD4+ T cell responses. These CD4+ T cells produced γ-interferon (IFN-γ) and had the direct ability to kill tumors through granzyme B. Notably, downregulation of HOXB7 using siRNA enhanced human leukocyte antigen class II expression on tumor cells by decreasing the phosphorylation of MAPK. Mitogen-activated protein kinase inhibition augmented IFN-γ production by HOXB7-reactive CD4+ T cell responses without decreasing the expression of HOXB7. These results suggest that combining HOXB7 peptide-based vaccine with MAPK inhibitors could be an effective immunological strategy for cancer treatment.

Long non-coding RNA BBOX1-AS1 exacerbates esophageal squamous cell carcinoma development by regulating HOXB7/ß-catenin axis.

Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/ß-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/ß-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches.

Circ_0068631 sponges miR-139-5p to promote the growth and metastasis of cutaneous squamous cell carcinoma by upregulating HOXB7.

BACKGROUND: Circular RNAs (circRNAs) are often dysregulated in cancers and closely related to cancer progression, including cutaneous squamous cell carcinoma (CSCC). However, the role and mechanism of circ_0068631 in CSCC progression have not been reported. METHODS: The expression of circ_0068631, microRNA-139-5p (miR-139-5p), and homeobox B7 (HOXB7) was measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, and colony formation assay were used to measure cell proliferation. Cell apoptosis was assessed by flow cytometry. Cell migration was detected by transwell assay. The interaction between miR-139-5p and circ_0068631 or HOXB7 was confirmed by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the function of circ_0068631 in vivo. RESULTS: Circ_0068631 was upregulated in CSCC tissues and cells, and its silencing could inhibit CSCC cell proliferation and metastasis while promoting apoptosis in vitro, as well as restrain CSCC tumor growth in vivo. Circ_0068631 acted as a sponge of miR-139-5p, and miR-139-5p inhibition reversed the repressive effect of circ_0068631 knockdown on CSCC cell progression. Furthermore, HOXB7 was a target of miR-139-5p, and miR-139-5p inhibited the malignant behaviors by downregulating HOXB7 expression in CSCC cells. Further, circ_0068631 sponged miR-139-5p to regulate HOXB7 expression. CONCLUSION: Circ_0068631 functioned as a novel oncogene in CSCC progression by regulating miR-139-5p/HOXB7 axis, suggesting that circ_0068631 may be a potential target for CSCC treatment. HIGHLIGHTS: Circ_0068631 was overexpressed in CSCC tissues and cells. Circ_0068631 downregulation suppressed CSCC progression via miR-139-5p. Circ_0068631 regulated HOXB7 via sponging miR-139-5p.

Propofol prevents the aggressive progression of oral squamous cell carcinoma via regulating circ_0005623/miR-195-5p/HOXB7 axis.

Oral squamous cell carcinoma (OSCC) is a general oral disease with high mortality. This study aimed to investigate the effects and underlying mechanism of propofol in OSCC. Propofol treatment inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), but promoted apoptosis and induced cell cycle arrest in OSCC cells. miR-195-5p was a target of circ_0005623 and directly targeted to HOXB7. Circ_0005623 and HOXB7 were upregulated, while miR-195-5p was downregulated in OSCC tissues and cells. Overexpression of circ_0005623 partly reversed the effects of propofol on cell proliferation, migration invasion, EMT, cell cycle progression, and apoptosis in SCC-9 and CAL-27 cells. Meanwhile, further investigation uncovered that circ_0005623 could act as a sponge for miR-195-5p to regulate HOXB7 expression, thereby mediating the suppression effects of propofol on OSCC cells. In vivo assay suggested that overexpression of circ_0005623 promoted tumor growth, which was inhibited by propofol treatment. Taken together, propofol regulated aggressive progression of OSCC via the circ_0005623/miR-195-5p/HOXB7 axis, providing the new train of thoughts for diagnosis and therapy of human OSCC.

HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma.

BACKGROUND: The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. METHODS: HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. RESULTS: Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients' overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. CONCLUSIONS: Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.

The opposite functions of miR-24 in the osteogenesis and adipogenesis of adipose-derived mesenchymal stem cells are mediated by the HOXB7/ß-catenin complex.

Adipose-derived mesenchymal stem cells (ADMSCs) used in combination with nanoparticles or scaffolds represent promising candidates for bone engineering. Compared to bone marrow-derived MSCs (BMMSCs), ADMSCs show a relatively low capacity for osteogenesis. In the current study, miR-24 was identified as an osteogenesis- and adipogenesis-related miRNA that performs opposing roles (inhibition in osteogenesis and promotion in adipogenesis) during these two differentiation processes. Through bioinformatics analysis and luciferase reporter assays, homeobox protein Hox-B7 (HOXB7) was identified as a potential novel downstream target of miR-24 that contains a miR-24 binding site in the 3'-UTR of its mRNA. Overexpression of HOXB7 could partly halt the inhibitory effect of miR-24 on osteogenesis, and downregulation of HOXB7 could also partly suppress the positive effect of miR-24 on adipogenesis. Furthermore, immunoprecipitation experiments found that HOXB7 and ß-catenin formed a functional complex that acted as an essential modulator during osteogenesis and adipogenesis of ADMSCs. After transfecting ADMSCs with an MSNs-PEI-miR-24 agomir or antagomir and loading the cells onto gelatin-chitosan scaffolds, the compounds were assessed for their abilities to repair the critical-sized calvarial defects in rats. Comprehensive evaluation, including micro-CT, sequential fluorescent labeling, and immunohistochemistry analysis, revealed that silencing miR-24 distinctly promoted in vivo bone remolding, whereas overexpression of miR-24 significantly repressed bone formation. Taken together, our findings demonstrated opposite roles for the miR-24/HOXB7/ß-catenin signaling pathway in the osteogenesis and adipogenesis of ADMSCs, which may provide a novel mechanism for determining the balance between these two biological processes.

Copy number variation in HOXB7 and HOXB8 involves in the formation of beard trait in chickens.

The derived feathering phenotype beard in domestic birds is an ideal resource to investigate the genetic mechanisms controlling feather development and differentiation. In the present study, we performed a GWAS and QTL linkage analysis on the trait of beard in Beijing fatty chicken. One major QTL (1.2-1.9 Mb) was identified that could explain 34% of the phenotypic variation. The copy number variation that was copied from the region (GGA27:3 578 409-3 592 890 bp) containing homebox B7 (HOXB7) and homebox B8 (HOXB8) was validated to be only exhibited in the genome of bearded chickens. Protein-protein interaction analysis indicated that HOXB7 and HOXB8 proteins could highly interact with the HOXB family members, including HOXB4, HOXB5 and HOXB6, whose genomic locations near HOXB7 and HOXB8 suggested that they may regulate their family members to involve in the formation of the beard trait in chickens. Overall, our work provides basic data for understanding the mechanisms regulating beard development and differentiation.

The relationship between homeobox B7 expression and the clinical characteristics of patient with prostate cancer.

BACKGROUND: The prognosis of patients with prostate cancer (PCa) remains poor. METHODS: GSE16560, GSE32448, GSE79957, GSE17951, and TCGA-PRAD were reanalyzed to evaluate the expression of homeobox B7 (HOXB7) between PCa tissues and normal prostate tissues and to characterize the correlation between the expression of HOXB7 and the clinicopathological features of patients with PCa. Gene set enrichment analysis was conducted to investigate the mechanisms. RESULTS: HOXB7 was upregulated in PCa tissues (P = 0.0005). Both the univariate and multivariate analyses demonstrated that the expression of HOXB7 was correlated with the Gleason score and TNM staging of patients with PCa. The Gleason score and TNM staging were higher in the HOXB7 high expression group. The overall survival (hazard ratio [HR] = 0.632; 95% confidence interval [CI]: 0.4773-0.8369; P = 0.0014) and progression-free survival (HR = 0.544; 95% CI: 0.3157-0.9373; P = 0.0283) favored patients with PCa in HOXB7 low expression group over those in HOXB7 high expression group. PCa samples in HOXB7 low expression group were enriched in gene sets associated with the epithelial mesenchymal transition, apical junction, angiogenesis, ultraviolet response, and hypoxia. CONCLUSIONS: HOXB7 might be an independent prognostic factor of patients with PCa.

Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/ß-catenin signaling pathway.

Metastatic cutaneous squamous cell carcinoma (CSCC) is a major cause of death associated with nonmelanoma skin cancer. The involvement of homeobox B7 ( HOXB7) in cancers has been reported. Thus, the current study intends to explore the effect of HOXB7 on CSCC and its relationship with the Wnt/ß-catenin signaling pathway. Initially, microarray-based gene expression profiling of CSCC was performed, and HOXB7 was identified as an upregulated gene based on the microarray data of GSE66359 . Following this, the experimental results indicated that HOXB7 and ß-catenin formed a composite, demonstrating that endogenous HOXB7 binds to ß-catenin. Subsequently, CSCC cells were treated with siRNA against HOXB7 or an inhibitor of the Wnt/ß-catenin signaling pathway to analyze any underlying regulatory mechanism of HOXB7 on the CSCC cells. Tumor growth involving xenografts in nude mice was also observed so as to explore whether or not HOXB7 could regulate subcutaneous tumor growth through in vivo culturing. To investigate the potential effects of HOXB7 on the Wnt/ß-catenin signaling pathway, we determined the expression of HOXB7 and downstream genes of the Wnt/ß-catenin signaling pathway. Notably, siRNA-mediated knockdown of HOXB7 inhibited the activation of the Wnt/ß-catenin signaling pathway, thereby impeding the progression of cell viability, migration, and invasion as well as of the tumor growth, although contrarily facilitating cell apoptosis. Taken together, silencing of the HOXB7 has the mechanism of inactivating the Wnt/ß-catenin signaling pathway, thereby accelerating cell apoptosis and suppressing cell migration and invasion in CSCC, which could provide a candidate target for the CSCC treatment.

Upregulation of HOXB7 promotes the tumorigenesis and progression of gastric cancer and correlates with clinical characteristics.

Several examples of aberrant homeobox gene expression have been found across a range of cancers, and it is also confirmed that homeobox genes play a critical roles in tumorigenesis and progression. Notwithstanding homeobox B7 (HOXB7) has been documented that its deregulation promotes carcinogenesis and development in gastrointestinal tract, its function in gastric cancer has not been investigated. In this study, HOXB7 expression was examined to be distinctly upregulated in gastric carcinoma GC cell lines and in the tumor relative to normal gastric tissue. High HOXB7 expression was correlated with tumor differentiation (P = 0.025) and TNM stage (P = 0.008). HOXB7 knockdown in BGC-823 and SGC-7901 resulted in decreased migration and invasion with alteration of epithelial-mesenchymal transition (EMT) proteins and influenced proliferation, apoptosis, and cell cycle. Furthermore, complementary DNA (cDNA) microarray, qPCR, and Western blotting were performed to explore potential downstream target genes of HOXB7. HOXB7 is generally overexpressed in GC, associated with patient clinical characteristics, and specifically promotes GC cell malignant biological properties through PIK3R3/AKT signaling pathways, indicating HOXB7 as a causal factor in promoting tumor progression.

Immunoexpression of hoxb7 and hoxb9 in salivary gland tumours.

BACKGROUND: Salivary gland carcinomas are uncommon neoplasms and the identification of new prognostic indicators could improve their management. HOXB7 and HOXB9 are members of the class I homeobox-containing genes important for normal embryogenesis and that are dysregulated in several human neoplasms. This study investigated HOXB7 and HOXB9 expressions in salivary gland tumourigenesis, their correlation with neoplastic proliferative and angiogenic features and their importance as prognostic markers. METHODS: A hundred and fifty salivary gland tumours were organized in tissue microarray and expressions of CD105, Ki67, HOXB7 and HOXB9 were determined through immunohistochemistry. Reactions were quantified and correlated with clinicopathological parameters. RESULTS: In normal glands, HOXB7 was found in basal cells, whereas HOXB9 was seen in serous acinar and scattered ductal cells. Malignancies exhibited an increased vascular density, proliferative index, HOXB7 and HOXB9 expressions when compared with pleomorphic adenoma and Warthin's tumour. Significant correlation was found between HOXB7 and CD105 (P = 0.004) in adenoid cystic carcinomas, and HOXB7 higher expression significantly correlated with the presence of paresthesia (P = 0.02). No marker exhibited a significant association with survival rates (P > 0.05). CONCLUSION: HOXB7 and HOXB9 were expressed in normal salivary gland and were present in benign and malignant tumours derived from these structures, and HOXB7 significantly correlated with neoangiogenesis in AdCC. These findings suggest that both proteins might play a role in salivary gland tumourigenesis, but they were not significant prognostic determinants in this sample.

The roles of HOXB7 in promoting migration, invasion, and anti-apoptosis in gastric cancer.

BACKGROUND AND AIM: The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells. METHODS: Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay were performed, and Akt/PTEN activity was measured by western blotting. RESULTS: Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells. CONCLUSION: Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects.

Differential Expression of Hox and Notch Genes in Larval and Adult Stages of Echinococcus granulosus.

This investigation aimed to evaluate the differential expression of HoxB7 and notch genes in different developmental stages of Echinococcus granulosus sensu stricto. The expression of HoxB7 gene was observed at all developmental stages. Nevertheless, significant fold differences in the expression level was documented in the juvenile worm with 3 or more proglottids, the germinal layer from infected sheep, and the adult worm from an experimentally infected dog. The notch gene was expressed at all developmental stages of E. granulosus; however, the fold difference was significantly increased at the microcysts in monophasic culture medium and the germinal layer of infected sheep in comparison with other stages. The findings demonstrated that the 2 aforementioned genes evaluated in the present study were differentially expressed at different developmental stages of the parasite and may contribute to some important biological processes of E. granulosus.

Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer.

HOXB7 encodes a transcription factor that is overexpressed in a number of cancers and encompasses many oncogenic functions. Previous results have shown it to promote cell proliferation, angiogenesis, epithelial-mesenchymal transition, DNA repair and cell survival. Because of its role in many cancers and tumorigenic processes, HOXB7 has been suggested to be a potential drug target. However, HOXB7 binding sites on chromatin and its targets are poorly known. The aim of our study was to identify HOXB7 binding sites on breast cancer cell chromatin and to delineate direct target genes located nearby these binding sites. We found 1,504 HOXB7 chromatin binding sites in BT-474 breast cancer cell line that overexpresses HOXB7. Seventeen selected binding sites were validated by ChIP-qPCR in several breast cancer cell lines. Furthermore, we analyzed expression of a large number of genes located nearby HOXB7 binding sites and found several new direct targets, such as CTNND2 and SCGB1D2. Identification of HOXB7 chromatin binding sites and target genes is essential to understand better the role of HOXB7 in breast cancer and mechanisms by which it regulates tumorigenic processes.

Role of HOXB7 in regulation of progression and metastasis of human lung adenocarcinoma.

Dysregulation of homeobox B7 (HOXB7), a member of the homeobox genes family, was suggested to play a role in regulation of tumorigenesis and metastases of some cancers. However, the functions of HOXB7 in association with lung adenocarcinoma (LAC) have not been investigated. The correlation between the level of HOXB7 expression and cancer progression in patients is not known. In this study, through analysis of 75 LAC samples and their corresponding normal lung epithelium tissues immunohistochemistry (IHC), we demonstrate that HOXB7 was overexpressed in LAC specimens compared to their paired normal lung epithelium tissues. Increased expression of HOXB7 was associated with poor clinical outcomes, correlating significantly with a short survival time in patients who had LAC. Moreover, HOXB7 expression level was correlated with the tumor status (P = 0.028), nodal status (P = 0.012) and tumor stage (P = 0.029) in lung adenocarcinoma. Silencing HOXB7 inhibited cell growth and metastases in vitro and in vivo. In conclusion, our results suggest that HOXB7 promotes LAC progression by enhancing proliferation and metastasis. The increased expression of HOXB7 in LAC is a potential prognostic indicator for patients, and HOXB7 could be a novel target for treatment of LAC patients.

Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study.

BACKGROUND: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. METHODS: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. RESULTS: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50-75%)-measured with high-resolution computer tomography-compared to those with a lower extent (0-25%) (difference between means = 25.74 ± 6.72, p = 0.004). CONCLUSIONS: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

Unveiling HOXB7 as a novel diagnostic and prognostic biomarker through pan-cancer computer screening.

We attempted to investigate the role of HOXB7 in tumor progression and evolution by means of an extensive computer screening analysis of various cancer types. We performed univariate Cox regression and Kaplan-Meier survival analyses to assess the impact of HOXB7 on overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in different types of cancer. Furthermore, we examined the relationship between HOXB7 and several clinical features: tumor microenvironment, immune regulatory genes, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). We performed gene set enrichment analysis to gain deeper insights into the potential molecular mechanisms of HOXB7, and validated our findings through functional assays in cells, including methyl thiazolyl tetrazolium cytotoxicity and Transwell invasion assays. HOXB7 expression was associated with different clinical characteristics in numerous malignancies. Higher HOXB7 expression was associated with worse OS, DSS, and PFI in some cancer types. In particular, HOXB7 expression was favorably associated with immune cell infiltration, immune regulatory genes, immunological checkpoints, TMB, and MSI in malignancies. Furthermore, we identified a strong link between copper death-associated gene expression and HOXB7 expression. According to the findings of this study, HOXB7 might serve as an appealing focus for tumor diagnosis and immunotherapy and a prospective indicator of prognosis.

Differential and Prognostic Significance of HOXB7 in Gliomas.

Diffuse glioma is the most common primary tumor of the central nervous system. The prognosis of the individual tumor is heavily dependent on its grade and subtype. Homeobox B7 (HOXB7), a member of the homeobox family, is abnormally overexpressed in a variety of tumors. However, its function in glioma is unclear. In this study, HOXB7 mRNA and protein expression levels were analyzed in 401 gliomas from the CGGA RNA-seq database (325 cases) and our hospital (76 cases). HOXB7 expression, at both mRNA and protein levels, were upregulated in glioblastoma (GBM) and isocitrate dehydrogenase 1 (IDH1) wild-type glioma tissues. Kaplan-Meier with log-rank test showed that patients with high HOXB7 expression had a poor prognosis (p < 0.0001). Moreover, HOXB7 protein was deleted in 90.9% (20/22) of oligodendrogliomas and 13.0% (3/23) of astrocytomas. The sensitivity and specificity of HOXB7 protein deletion in oligodendroglioma were 90.9% (20/22) and 87.0% (20/23), respectively. To verify the reliability of using HOXB7 in differentiating oligodendroglioma, we used 1p/19q fluorescence in situ hybridization (FISH) testing as a positive control. The Cohen's kappa coefficient of HOXB7 immunohistochemistry staining and 1p/19q FISH testing was 0.778 (95% CI: 0.594-0.962, p < 0.001). In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.