Bioinformatics analysis of the role of aldolase A in tumor prognosis and immunity

Tian, Wanjia; Zhou, Junying; Chen, Mengyu; Qiu, Luojie; Li, Yike; Zhang, Weiwei; Guo, Ruixia; Lei, Ningjing; Chang, Lei

doi:10.1038/s41598-022-15866-4

Cited by 16 publications

(10 citation statements)

References 47 publications

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“…ALDOA, a glycolytic enzyme targeted by HIF1 has been also reported to play a significant role in malignancies (30). Based on current literature, high levels of ALDOA promote tumor growth and metastatic potential (31). Similarly to HIF1, we found ALDOA to be up-regulated, a finding that is in accordance with two studies (10,11) that were performed in Asian populations concerning ccRCC.…”

Section: Discussionsupporting

confidence: 89%

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The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma

Grammatikaki¹,

Katifelis²,

Stravodimos³

et al. 2023

In Vivo

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Background/Aim: Renal cell carcinoma is one of the three most common malignant urologic tumors, with clear cell renal cell carcinoma (ccRCC) representing its most common subtype. Although nephrectomy can radically cure the disease, a large percentage of patients is diagnosed when metastatic sites are present and thus alternative, pharmaceutical approaches need to be sought. Since HIF1 upregulates the transcription of genes that range from metabolic enzymes to non-coding RNAs, and is a key molecule of ccRCC pathogenesis, this study aimed to investigate the expression ALDOA, SOX-6, and non-coding RNAs (mir-122, mir-1271, and MALAT-1) in samples from ccRCC patients. Patients and Methods: Tumor and adjacent normal tissue samples from 14 patients with ccRCC were harvested. Expression of ALDOA, mir-122, mir-1271, and MALAT-1 mRNA was estimated using real time PCR, whereas the expression of SOX-6 protein was investigated using immunohistochemistry. Results: Upregulation of HIF1 was observed, accompanied with upregulation of ALDOA, On the contrary, the expression of mir-1271 was found to be reduced, a finding that can be attributed to a potential MALAT-1 sponge function. Furthermore, SOX-6 protein levels (a transcription factor with tumor suppressing properties) were also reduced. Conclusion: The observed dysregulated expression levels highlight the importance of ALDOA, MALAT-1, mir-122, mir-1271, and SOX-6, which remain less studied than the known and well-studied HIF1 pathways of VEGF, TGF-α, and EPO. Furthermore, inhibition of the upregulated ALDOA, mir-122, and MALAT-1 could be of therapeutic interest for selected ccRCC patients.

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Section: Discussionsupporting

confidence: 89%

“…Similarly to HIF1, we found ALDOA to be up-regulated, a finding that is in accordance with two studies (10,11) that were performed in Asian populations concerning ccRCC. Despite the lack of additional studies in ccRCC, literature shows that increased expression of ALDOA is linked with reduced survival in several malignancies (31,32).…”

Section: Discussionmentioning

confidence: 99%

The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma

Grammatikaki¹,

Katifelis²,

Stravodimos³

et al. 2023

In Vivo

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“…At the same time, in epileptic brain tissue, it is mainly expressed in macrophages and astrocytes. It has been demonstrated that the ALDOA gene is associated with macrophage and T lymphocyte infiltration (58), while astrocytes are also associated with central nervous system inflammation (59). Our results allow us to hypothesize that the ALDOA gene is involved in neuroinflammation through astrocytes and macrophages, affecting sympathetic and metabolic activities through neuroinflammation.…”

Section: Discussionsupporting

confidence: 53%

Single-cell sequencing combined with machine learning reveals the mechanism of interaction between epilepsy and stress cardiomyopathy

Pei²,

Zhang³

et al. 2023

Front. Immunol.

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BackgroundEpilepsy is a disorder that can manifest as abnormalities in neurological or physical function. Stress cardiomyopathy is closely associated with neurological stimulation. However, the mechanisms underlying the interrelationship between epilepsy and stress cardiomyopathy are unclear. This paper aims to explore the genetic features and potential molecular mechanisms shared in epilepsy and stress cardiomyopathy.MethodsBy analyzing the epilepsy dataset and stress cardiomyopathy dataset separately, the intersection of the two disease co-expressed differential genes is obtained, the co-expressed differential genes reveal the biological functions, the network is constructed, and the core modules are identified to reveal the interaction mechanism, the co-expressed genes with diagnostic validity are screened by machine learning algorithms, and the co-expressed genes are validated in parallel on the epilepsy single-cell data and the stress cardiomyopathy rat model.ResultsEpilepsy causes stress cardiomyopathy, and its key pathways are Complement and coagulation cascades, HIF-1 signaling pathway, its key co-expressed genes include SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3. The key immune cell subpopulations localized by single-cell data are the T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup.ConclusionWe believe epilepsy causing stress cardiomyopathy results from a multi-gene, multi-pathway combination. We identified the core co-expressed genes (SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3) and the pathways that function in them (Complement and coagulation cascades, HIF-1 signaling pathway, JAK-STAT signaling pathway), and finally localized their key cellular subgroups (T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup). Also, combining cell subpopulations with hypercoagulability as well as sympathetic excitation further narrowed the cell subpopulations of related functions.

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“… 34 High expression of ALDOA was related to poor prognosis in breast cancer. 35 A mutation in DNAH7 was reported in male infertility with severe asthenozoospermia. 36 , 37 ADAP1 was associated with the progression and prognosis of squamous cell carcinoma and lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy

Zhang,

Liu

et al. 2023

DDDT

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Objective Genomic profiles relating to H101 treatment-induced alterations are yet to be achieved. Here, we evaluated the impact of H101 via exome-sequencing approaches aiming to probe for potential biomarkers that are actionable in the treatment of persistent/recurrent/metastatic (P/R/M) cervical cancer. Methods Whole exome sequencing (WES) was performd on paired pre- and post-H101 samples from 17 P/R/M cervical cancer patients who received serial intra-tumor injections of H101. Somatic mutations, including high-frequency mutations, microsatellite instability (MSI) status, tumor mutation burden (TMB), clonal evolution, and mutational signature were analyzed. Results The median follow-up time after the H101 treatment was 14 months. Complete response was achieved in 9 patients, 3 patients achieved partial response, and 2 patients had stable disease, resulting in an objective response rate (ORR) of 70.6% (95% CI: 46.4%-96.7%). WES analysis showed no difference in treatment-related mutation characteristics, including non-synonymous-SNVs and TMB status. Patients with lower TMB were correlated with improved H101 response rates ( P =0.044), whereas the same was not evident in high MSI (MSI-H) versus non-MSI-H patients ( P =0.528). We observed a few high-frequency mutation genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) that probably carry functional importance in response to H101 treatment, among which KMT2D and ADAP1 mutations were associated with inferior progression-free survival (PFS) and/or overall survival (OS) ( P <0.05). Notably, H101 treatment-induced accumulating subclones or clusters in primary tumors and some (Signature 2) were associated with shorter PFS. Conclusion We conducted an unprecedented work via a WES-based approach and provided preliminary insights into H101 treatment-induced genetic aberrations in which some genes (TTN, KMT2D, ALDOA, DNAH7, ADAP1, PTPN23, and THEMIS2) could be considered potential therapeutic targets of H101-containing treatment in cervical carcinoma. Moreover, the therapy-associated characteristics such as clonal evolution and a mutational signature may warrant further evaluation of H101 in clinical settings for treating cervical carcinoma.

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Bioinformatics analysis of the role of aldolase A in tumor prognosis and immunity

Cited by 16 publications

References 47 publications

The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma

The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma

Single-cell sequencing combined with machine learning reveals the mechanism of interaction between epilepsy and stress cardiomyopathy

Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy

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