Diagnostic and Prognostic Value of
            <i>HOXC</i>
            Family Members in Gastric Cancer

Wang, Mei-Qian; Yin, Qi-Yun; Chen, Yi-Ru; Zhu, Shuchai

doi:10.2217/fon-2021-0291

Cited by 8 publications

(8 citation statements)

References 60 publications

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“…In pediatric glioma tissues, overexpression of HOX genes in general is associated with favorable prognosis, higher immune infiltration, and better response to immunotherapy [60]. Abnormal overexpression of HOXC4 in different types of cancer (pancancer study), including SqCLC, suggests that HOXC4 may function as an oncogene and could be used as a diagnostic and prognostic biomarker [61]. Finally, we have identified the GSTZ1 gene to be associated with better OS in SqCLC patients.…”

Section: Discussionmentioning

confidence: 87%

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)

Šutić,

Dmitrović,

Jakovčević

et al. 2024

Cancers

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Squamous cell lung carcinoma (SqCLC) is associated with high mortality and limited treatment options. Identification of therapeutic targets and prognostic biomarkers is still lacking. This research aims to analyze the transcriptomic profile of SqCLC samples and identify the key genes associated with tumorigenesis, overall survival (OS), and a profile of the tumor-infiltrating immune cells. Differential gene expression analysis, pathway enrichment analysis, and Gene Ontology analysis on RNA-seq data obtained from FFPE tumor samples (N = 23) and healthy tissues (N = 3) were performed (experimental cohort). Validation of the results was conducted on publicly available gene expression data using TCGA LUSC (N = 225) and GTEx healthy donors’ cohorts (N = 288). We identified 1133 upregulated and 644 downregulated genes, common for both cohorts. The most prominent upregulated genes were involved in cell cycle and proliferation regulation pathways (MAGEA9B, MAGED4, KRT, MMT11/13), while downregulated genes predominately belonged to immune-related pathways (DEFA1B, DEFA1, DEFA3). Results of the survival analysis, conducted on the validation cohort and commonly deregulated genes, indicated that overexpression of HOXC4 (p < 0.001), LLGL1 (p = 0.0015), and SLC4A3 (p = 0.0034) is associated with worse OS in early-stage SqCLC patients. In contrast, overexpression of GSTZ1 (p = 0.0029) and LILRA5 (p = 0.0086) was protective, i.e., associated with better OS. By applying a single-sample gene-set enrichment analysis (ssGSEA), we identified four distinct immune subtypes. Immune cell distribution suggests that the memory T cells (central and effector) and follicular helper T cells could serve as important stratification parameters.

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Section: Discussionmentioning

confidence: 87%

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)

Šutić,

Dmitrović,

Jakovčević

et al. 2024

Cancers

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“…Based on the literature research, several members of the HOXC family have been well studied for their role in gastric cancer ( 20 , 21 ), however, HOXC8 has not been fully elucidated for its role in regulating gastric cancer progression. Thus, we firstly examined if HOXC8 was dysregulated in the gastric cancer cells.…”

Section: Resultsmentioning

confidence: 99%

The Role of miR-4256/HOXC8 Signaling Axis in the Gastric Cancer Progression: Evidence From lncRNA-miRNA-mRNA Network Analysis

Zhong

Liu

et al. 2022

Front. Oncol.

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Gastric cancer is a deadly human malignancy and the molecular mechanisms underlying gastric cancer pathophysiology are very complicated. Thus, further investigations are warranted to decipher the underlying molecular mechanisms. With the development of high-throughput screening and bioinformatics, gene expression profiles with large scale have been performed in gastric cancer. In the present study, we mined The Cancer Genome Atlas (TCGA) database and analyzed the gene expression profiles between gastric cancer tissues and normal gastric tissues. A series of differentially expressed lncRNAs, miRNAs and mRNAs between gastric cancer tissues and normal gastric tissues were identified. Based on the differentially expressed genes, we constructed miRNA-mRNA network, lncRNA-mRNA network and transcriptional factors-mRNA-miRNA-lncRNA network. Furthermore, the Kaplan survival analysis showed that high expression levels of EVX1, GBX2, GCM1, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12 and HOXC13 were all significantly correlated with shorter overall survival of the patients with gastric cancer. On the other hand, low expression level of HOXA13 was associated with shorter overall survival of patients with gastric cancer. Among these hub genes, we performed the in vitro functional studies of HOXC8 in the gastric cancer cells. Knockdown of HOXC8 and overexpression of miR-4256 both significantly repressed the gastric cancer cell proliferation and migration, and miR-4256 repressed the expression of HOXC8 via targeting its 3’ untranslated region in gastric cancer cells. Collectively, our results revealed that a complex interaction networks of differentially expressed genes in gastric cancer, and further functional studies indicated that miR-4256/HOXC8 may be an important axis in regulating gastric cancer progression.

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“…21 Despite ongoing advancements in clinical treatment strategies, most patients with GC have a low overall cure rate. 22 With the development of biomolecular technology, circRNAs have been recognized for their significant role in cancer progression. 23,24 In this experiment, we explored the molecular mechanism of circTMEM87A and highlighted its potential as a therapeutic target for GC.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, surgery, chemotherapy, and targeted therapy are the primary treatment methods for GC 21 . Despite ongoing advancements in clinical treatment strategies, most patients with GC have a low overall cure rate 22 . With the development of biomolecular technology, circRNAs have been recognized for their significant role in cancer progression 23,24 .…”

Section: Discussionmentioning

confidence: 99%

CircTMEM87A promotes the tumorigenesis of gastric cancer by regulating the miR‐1276/SLC7A11 axis

Dong,

Chen,

Zhao

et al. 2023

J of Gastro and Hepatol

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BackgroundGastric cancer (GC) is a common malignancy with high incidence and mortality, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the molecular mechanism of circTMEM87A in GC malignant progression is uncertain.MethodsQuantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to detect the expressions of circTMEM87A, miR‐1276, and solute carrier family 7 membrane 11 (SLC7A11). Western blot was applied to detect protein expression levels of EMT‐related proteins (vimentin and E‐cadherin) and SLC7A11. Cell counting kit‐8 assay (CCK8) and thymidine analog 5‐ethynyl‐2′‐deoxyuridine (EdU) were performed to assess cell proliferation. Apoptosis was investigated using flow cytometry. Transwell assay and wound healing assay were carried out to examine the migration of MKN‐7 and AGS cells. The Cellular ROS Assay Kit, Iron Assay Kit, and GSH/GSSG Ratio Detection Assay Kit were utilized to monitor lipid ROS level, iron level, and GSH/GSSG ratio, respectively. The interaction between miR‐1276 and circTMEM87A or SLC7A11 was investigated using dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft mouse model was constructed to explore the function of circTMEM87A in tumor formation in vivo.ResultsCircTMEM87A and SLC7A11 were upregulated, while miR‐1276 was downregulated in GC tissues and cells. Knockdown of circTMEM87A suppressed the proliferation and migration and promoted apoptosis and ferroptosis of GC cells. CircTMEM87A served as a sponge for miR‐1276, and miR‐1276 inhibitor relieved the circTMEM87A knockdown‐induced effects on GC cell phenotypes. Similarly, SLC7A11, a downstream gene of miR‐1276, rescued miR‐1276 overexpression‐induced effects on GC cell function. Furthermore, circTMEM87A knockdown inhibited GC cell tumor phenotypes in vivo.ConclusionCircTMEM87A promoted the proliferation and migration and inhibited apoptosis and ferroptosis of GC cells by increasing SLC7A11 expression through binding to miR‐1276.

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Diagnostic and Prognostic Value of HOXC Family Members in Gastric Cancer

Cited by 8 publications

References 60 publications

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)

Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC)

The Role of miR-4256/HOXC8 Signaling Axis in the Gastric Cancer Progression: Evidence From lncRNA-miRNA-mRNA Network Analysis

CircTMEM87A promotes the tumorigenesis of gastric cancer by regulating the miR‐1276/SLC7A11 axis

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