SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC

Ko, Eungil; Kim, Jong Seo; Bae, Jong Woo; Kim, Jeesoo; Park, Sung‐Gyoo; Jung, Gyuweon

doi:10.1016/j.redox.2019.101217

Cited by 30 publications

(23 citation statements)

References 43 publications

(61 reference statements)

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“…In agreement with this finding, Luo et al 13 reported that expression of SERPINA3 was correlated with poor survival in glioma patients, as evaluated by immunohistochemistry. Recent studies have shown that SERPINA3 acts as a key molecule for survival prediction in various cancers 11,20 . The present study not only demonstrates that SERPINA3 is a negative prognostic indicator, but also that it has a valuable prognostic performance for 1‐, 3‐, and 5‐year survival.…”

Section: Discussionsupporting

confidence: 63%

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

Yuan

Wang

Zhang

et al. 2021

Immunity Inflam & Disease

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Introduction The prognosis of patients with glioma is dismal. It has been reported that Serpin peptidase inhibitor clade A member 3 (SERPINA3) is associated with the mobility and invasion of tumor cells. Our study was designed to explore the value of SERPINA3 messenger RNA (mRNA) expression in the biological process, prognosis, and immune significance in glioma. Methods We analyzed the biological functions of SERPINA3 through data from the Chinese Glioma Genome Atlas databases. Differentially expressed genes and enrichment analysis were performed and correlations between SERPINA3 expression and immune cell infiltration were analyzed. Further, we validated the expression and the survival prediction role of SERPINA3 by using tissue microarrays and RNAscope in situ hybridization in 321 gliomas. The correlations between the expression and clinical‐pathological parameters as well as other biomarkers were examined. Results Univariate and multivariate regression both indicated that the level of SERPINA3 transcript represented an independent prognostic factor. High levels of SERPINA3 correlated with poor survival in patients with glioma. Expression of SERPINA3 mRNA was observed positively correlated with MCM6, IGFBP2, and FKBP10. Enrichment analysis showed SERPINA3 mainly enriched in immune‐related terms and signaling pathways including MAPK, TNF, P53, PI3K‐Akt, nuclear factor‐κB. Immune infiltration analysis further declare the SERPINA3 expression negatively correlated with levels of Macrophages M1, native CD4+ T cell, monocytes, and Mast cell activated. And overexpression of SERPINA3 correlated with low CD4+ T cell infiltration in glioma tissues. Conclusions SERPINA3 may play a key role in the biological process of glioma cells especially in immune suppression activities. SERPINA3 may serve as an independent survival prediction factor in glioma patients.

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Section: Discussionsupporting

confidence: 63%

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

Yuan

Wang

Zhang

et al. 2021

Immunity Inflam & Disease

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“…In addition, studies have found that knocking down RAC2 can inhibit the progression of osteosarcoma by inhibiting the wnt signaling pathway [ 24 ]. Besides, the up regulation of hnRNP-K transcriptional activity mediated by SERPINA3 promotes the survival and proliferation of HCC cells, which may be an indicator of poor prognosis in HCC patients [ 25 ]. So far, overexpression of SERPINA3 has been observed in several cancer types including breast cancer and the high expression level has been demonstrated to positively correlate with poor prognosis in patients with breast cancer, which means SERPINA3 can be associated with a shorter OS [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and development of an independent immune-related genes prognostic model for breast cancer

et al. 2021

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Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.

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“…Its high expression has been demonstrated to positively correlate with poor prognosis in patients with colon [26], breast [27], lung [28,29] and gastric cancers [30]. Recently, a new role for SERPINA3 was discovered as a transcriptional regulator of genes related to hepatocellular carcinoma progression by inducing telomere elongation, cell proliferation, migration and invasion [31]. SERPINA3 has been reported to be estrogen-inducible, and its mRNA level has been suggested to be significant predictor of good prognosis in hormone receptor (ER and/or PR)-positive breast cancer patients [25].…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer

Koivuluoma

Tervasmäki

Kauppila

et al. 2021

European Journal of Cancer

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Background: Breast cancer is strongly influenced by hereditary risk factors. Yet, the known susceptibility genes and genomic loci explain only about half of the familial component of the disease. To identify novel breast cancer predisposing gene defects, here we have performed massive parallel sequencing for Northern Finnish breast cancer cases. Methods: Ninety-eight breast cancer cases with indication of hereditary disease susceptibility were exome sequenced. Data filtering strategy focused on predictably deleterious rare variants that were still enriched in the sequenced cohort. Findings were confirmed with additional, geographically matched breast cancer cohorts. Results: A recurrent heterozygous splice acceptor variant, c.918-1G>C, in SERPINA3, was identified, and it was significantly enriched both in the hereditary (6/201, 3.0%, p Z 0.006, OR 5.1, 95% CI 1.7e14.8) and unselected breast cancer cohort (26/1569, 1.7%, p Z 0.009, OR 2.8, 95% CI 1.3e6.2). SERPINA3 c.918-1G>C carriers were also significantly more likely to have a rare tumor subtype, medullary breast cancer, than the non-carriers (4/26, 15.4%, p Z 0.000014, OR 42.9, 95% CI 11.7e157.1).

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SERPINA3 is a key modulator of HNRNP-K transcriptional activity against oxidative stress in HCC

Cited by 30 publications

References 43 publications

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

Identification and development of an independent immune-related genes prognostic model for breast cancer

Exome sequencing identifies a recurrent variant in SERPINA3 associating with hereditary susceptibility to breast cancer

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