Prognostic and Immunological Role of STK38 across Cancers: Friend or Foe?

Liu, Yankuo; Shi, Zhiyuan; Zheng, Zeyuan; Li, Jinxin; Yang, Kunao; Xu, Chunlan; Liu, Qing; Gong, Zhicheng; Yang, Yi; Zhao, Yue; Xuan, Zuodong; Sun, Huimin; Shao, Chen

doi:10.3390/ijms231911590

Cited by 9 publications

(7 citation statements)

References 45 publications

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“…Within the TME, immune cell and stromal cell play important roles, emerging as crucial prognostic biomarkers for cancer patients [13]. Quantitative scores obtained from ImmuneScore and StromalScore provide insights into the proportion of immune and stromal components, while ESTIMATEScore provides both aspects.…”

Section: Immune Subtype and Tumor Microenvironment (Tme) Analysis Of ...mentioning

confidence: 99%

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Li,

Zhang,

Jin

et al. 2024

Preprint

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Introduction: Lung adenocarcinoma (LUAD) has drawn attention recently because of its poor prognosis, limited responsiveness to treatment, and lack of trustworthy markers for predicting its development or its response to treatment. It has been established that the pathophysiology and development of various diseases, including malignancies, are influenced by the elongation of the very-long-chain fatty acids gene family (ELOVLs), a collection of genes responsible for elongating saturated and polyunsaturated fatty acids. Unknown is the specific function of ELOVLs in LUAD. Thus, the goal of our research was to elucidate the immune response and prognostic significance linked to ELOVL genes in LUAD. Methods: Open-access resources such as the TCGA and GTEx datasets were used to analyze the gene expression of ELOVLs across various types of cancers. We investigated the prognostic significance of the ELOVL family using Kaplan-Meier analysis. The cBioPortal database was utilized to assess the ELOVLs' genetic mutation profile. Several techniques were employed to get an understanding into the connection between tumor immunity and ELOVL genes. The WebGestalt database was used to carry out the function and pathway enrichment study of the ELOVL family. Immunohistochemical staining was utilized for the purpose of experimental validation. Results: We observed a substantial increase in gene expression in ELOVL1, ELOVL2, ELOVL4, ELOVL6, and ELOVL7 when comparing LUAD tumor samples to normal tissues. The upregulation of ELOVL2, ELOVL6, and ELOVL7 has been linked to tumor development and worse clinical outcome. The relevance was further highlighted by our examination of the immune infiltration pattern, which revealed a robust relationship between ELOVL2 expression and mast cell, macrophage, naive B cell, and myeloid dendritic cell in LUAD. ELOVL6 expression exhibited close association with B cell, macrophage, mast cell, CD4+ memory T cell, neutrophil, NK cell, and follicular helper T cell in LUAD. ELOVL7 expression exhibited close association with B cell, macrophage, mast cell, CD4+ memory T cell in LUAD. Conclusions: This study showed the significant immunogenetic and prognostic importance of ELOVL2, ELOVL6, and ELOVL7 in LUAD. Our findings highlight the importance of these genes and imply that they could function as distinct prognostic markers. Their discovery as immunotherapeutic targets offers an important benefit in fighting against LUAD.

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Section: Immune Subtype and Tumor Microenvironment (Tme) Analysis Of ...mentioning

confidence: 99%

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Li,

Zhang,

Jin

et al. 2024

Preprint

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“…Tumor mutation burden (TMB) serves as a crucial metric, representing the cumulative count of somatic coding mutation within a specific cancer type. This metric stands as a significant determinant of the efficacy of immunotherapy in various human cancer types 11 . Alteration data of all TCGA patients were downloaded from the UCSC XENA database.…”

Section: Analysis Of Tumor Mutation Burden and Microsatellite Instabi...mentioning

confidence: 99%

Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration

Tao,

Cai

2024

Sci Rep

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Pyruvate dehydrogenase kinases (PDKs) play a key role in glucose metabolism by exerting negative regulation over pyruvate dehyrogenase complex (PDC) activity through phosphorylation. Inhibition of PDKs holds the potential to enhance PDC activity, prompting cells to adopt a more aerobic metabolic profile. Consequently, PDKs emerge as promising targets for condition rooted in metabolic dysregulation, including malignance and diabetes. However, a comprehensive exploration of the distinct contribution of various PDK family members, particularly PDK3, across diverse tumor types remain incomplete. This study undertakes a systematic investigation of PDK family expression patterns, forging association with clinical parameters, using data from the TCGA and GTEx datasets. Survival analysis of PDKs is executed through both Kaplan–Meier analysis and COX regression analysis. Furthermore, the extent of immune infiltration is assessed by leveraging the CIBERSORT algorithm. Our study uncovers pronounced genetic heterogeneity among PDK family members, coupled with discernible clinical characteristic. Significantly, the study establishes the potential utility of PDK family genes as prognostic indicators and as predictors of therapeutic response. Additionally, our study sheds light on the immune infiltration profile of PDK family. The results showed the intimate involvement of these genes in immune-related metrics, including immune scoring, immune subtypes, tumor-infiltrating lymphocytes, and immune checkpoints expression. In sum, the findings of this study offer insightful strategies to guide the therapeutic direction, aiming at leveraging the impact of PDK family genes in cancer treatment.

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“…These properties are reported to result not from the function of Kir2.1 as an ion channel but from its interaction with STK38 to inhibit ubiquitination and degradation of MEKK2, thereby enhancing MEKK2-MEK1/2-ERK1/2 (extra-cellular signal-regulated kinase 1/2) signaling cascade [ 65 ] ( Figure 2 ). Recently, a pan-cancer analysis of STK38 reveals that the expression of STK38 is associated with patient survival, immune cell infiltration such as NK cells, cancer-associated fibroblasts, tumor mutation burden and microsatellite instability in several human cancers [ 66 ]. However, there is also evidence that STK38 can reduce the cell proliferation of glioblastomas and inhibit the metastasis of prostate cancer [ 67 ].…”

Section: Involvement Of Stk38 In Malignancymentioning

confidence: 99%

The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization

Fukasawa

Enomoto

Yoshizaki‐Ogawa

et al. 2023

Cancers

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Protein kinases, found in the nucleus and cytoplasm, play essential roles in a multitude of cellular processes, including cell division, proliferation, apoptosis, and signal transduction. STK38 is a member of the protein kinase A (PKA)/PKG/PKC family implicated in regulating cell division and morphogenesis in yeast and C. elegans. However, its function remained largely unknown in mammals. In recent years, advances in research on STK38 and the identification of its substrates has led to a better understanding of its function and role in mammals. This review discusses the structure, expression, and regulation of activity as a kinase, its role in the DNA damage response, cross-talk with other signaling pathways, and its application for radio-sensitization.

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Prognostic and Immunological Role of STK38 across Cancers: Friend or Foe?

Cited by 9 publications

References 45 publications

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Integrative Analysis of Prognostic Value and Immune Infiltration of ELOVL Gene Family in Lung Adenocarcinoma

Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration

The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization

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