Prognostic significance of KRT19 in Lung Squamous Cancer

Yi, Ming; Dong, Bing; Chu, Qian; Wu, Kongming

doi:10.7150/jca.51179

Cited by 15 publications

(3 citation statements)

References 41 publications

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“…It has been demonstrated that the evolutionarily old KRT19 is differentially expressed in several types of cancers. In the present study, KRT19 was found overexpressed in breast, colon, lung, liver and thyroid cancer ( Table 1 ), consistently with previous reports; KRT19 was associated with poor clinical outcomes in cancer patients as well ( Kawai et al, 2015 ; Saha et al, 2019 ; Wang et al, 2019 ; Yuan et al, 2021 ). KRT19 represents one of the factors determining tumor response to chemo/radiotherapy ( Bozionellou et al, 2004 ; Saha et al, 2018 ).…”

Section: Discussionsupporting

confidence: 92%

“In the light of evolution:” keratins as exceptional tumor biomarkers

Takan

Karakülah

Louka

et al. 2023

PeerJ

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Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into “soft” and “hard” keratins. They have a key role in several aspects of cancer pathophysiology, including cancer cell invasion and metastasis, and several members of the KRT family serve as diagnostic or prognostic markers. The human genome contains both, functional KRT genes and non-functional KRT pseudogenes, arranged in two uninterrupted clusters on chromosomes 12 and 17. This characteristic renders KRTs ideal for evolutionary studies. Herein, comprehensive phylogenetic analyses of KRT homologous proteins in the genomes of major taxonomic divisions were performed, so as to fill a gap in knowledge regarding the functional implications of keratins in cancer biology among tumor-bearing species. The differential expression profiles of KRTs in diverse types of cancers were investigated by analyzing high-throughput data, as well. Several KRT genes, including the phylogenetically conserved ones, were found to be deregulated across several cancer types and to participate in a common protein-protein interaction network. This indicates that, at least in cancer-bearing species, these genes might have been under similar evolutionary pressure, perhaps to support the same important function(s). In addition, semantic relations between KRTs and cancer were detected through extensive text mining. Therefore, by applying an integrative in silico pipeline, the evolutionary history of KRTs was reconstructed in the context of cancer, and the potential of using non-mammalian species as model organisms in functional studies on human cancer-associated KRT genes was uncovered.

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Section: Discussionsupporting

confidence: 92%

“In the light of evolution:” keratins as exceptional tumor biomarkers

Takan

Karakülah

Louka

et al. 2023

PeerJ

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“…8 Upregulation of KRT19 has been reported in various tumor tissues, and KRT19 is associated with tumor proliferation and metastasis, such as lung adenocarcinoma (LUAD), breast cancer (BRCA), hypopharyngeal squamous cell cancer and thyroid cancer (THCA). [9][10][11] However, the expression patterns of KRT19 and its clinical significance in OV remain unclear.…”

Section: Introductionmentioning

confidence: 99%

KRT19 is a Promising Prognostic Biomarker and Associates with Immune Infiltrates in Serous Ovarian Cystadenocarcinoma

Sun,

Zhou,

Dai

et al. 2023

IJGM

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Background Ovarian cancer (OV) is the highest prevalent gynecologic tumor with complicated pathogenesis; high-grade serous ovarian cystadenocarcinoma (HGSOC) is the most epidemiological and malignant subtype of OV. Keratin type I cytoskeleton 19 (KRT19) is an intermediate filament protein which plays essential roles in the maintenance of epithelial cells. However, its role in OV remains largely unknown. Methods Bioinformatic analysis with various databases was conducted in this study. In details, KRT19 expression was assessed using databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA). GO-KEGG and GSEA analysis were performed by R packages. The biological function of KRT19 was analyzed based on the single-cell sequencing information from CancerSEA database. The association of KRT19 expression with immunomodulator and chemokine was predicted via the TISIDB database. Results The expression of KRT19 was significantly upregulated in ovarian samples compared with normal controls. KRT19 expression was negatively associated with prognosis in OV, and further analysis revealed that KRT19 had promising diagnostic significance in distinguishing OV cancer from normal samples. GO-KEGG and GSEA analysis indicated that KRT19 was associated with multiple biological functions and pathways including epidermis development, apical junction, inflammatory response, and epithelial mesenchymal transition. By using different GEO series, we found that KRT19 was differentially expressed in OV-associated tissues. Furthermore, the increased KRT19 expression was positively correlated with the immune infiltration levels of the most immune cells in OV. Conclusion This study demonstrated that KRT19 is a promising prognosis and diagnosis biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in OV, suggesting being a molecular target for immunotherapies.

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“…In addition to MUC1, ELF3, B4GALT1, XBP1 and SLC2A1, 19 other genes (including KRT18, KRT19, KRT8, SFN, CLDN7, FKBP4, CCND1, ELOVL5, RHOD, SLC7A5, MED24, TPBG, AQP3, OVOL2, CISH, STC2, MREG, PMAIP1, and AREG) were screened by us to serve as early diagnostic markers of EC response to estrogen. To date, KRT18 [47], KRT19 [48], KRT8 [49], SFN [50], CLDN7 [51], FKBP4 [52], CCND1 [53], ELOVL5 [54], RHOD [55], SLC7A5 [56], MED24 [57], TPBG [58], AQP3 [59], OVOL2 [60], CISH [61], STC2 [62], PMAIP1 [63], and AREG [64] have been reported to be highly expressed in a variety of cancers and associated with the promotion of cancer cell growth, proliferation, migration and invasion. Only MREG was found to be downregulated in expression in thyroid cancer tissues, and knockdown of MREG promoted cancer cell proliferation and invasion [65].…”

Section: Plos Onementioning

confidence: 99%

Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers

Dong,

Zhao,

Liu

et al. 2024

PLoS ONE

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Background The development of endometrial cancer (EC) is closely related to the abnormal activation of the estrogen signaling pathway. Effective diagnostic markers are important for the early detection and treatment of EC. Method We downloaded single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST) data of EC from public databases. Enrichment scores were calculated for EC cell subpopulations using the “AddModuleScore” function and the AUCell package, respectively. Six predictive models were constructed, including logistic regression (LR), Gaussian naive Bayes (GaussianNB), k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and neural network (NK). Subsequently, receiver-operating characteristics with areas under the curves (AUCs) were used to assess the robustness of the predictive model. Result We classified EC cell coaggregation into six cell clusters, of which the epithelial, fibroblast and endothelial cell clusters had higher estrogen signaling pathway activity. We founded the epithelial cell subtype Epi cluster1, the fibroblast cell subtype Fib cluster3, and the endothelial cell subtype Endo cluster3 all showed early activation levels of estrogen response. Based on EC cell subtypes, estrogen-responsive early genes, and genes encoding Stage I and para-cancer differentially expressed proteins in EC patients, a total of 24 early diagnostic markers were identified. The AUCs values of all six classifiers were higher than 0.95, which indicates that the early diagnostic markers we screened have superior robustness across different classification algorithms. Conclusion Our study elucidates the potential biological mechanism of EC response to estrogen at single-cell resolution, which provides a new direction for early diagnosis of EC.

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Prognostic significance of KRT19 in Lung Squamous Cancer

Cited by 15 publications

References 41 publications

“In the light of evolution:” keratins as exceptional tumor biomarkers

“In the light of evolution:” keratins as exceptional tumor biomarkers

KRT19 is a Promising Prognostic Biomarker and Associates with Immune Infiltrates in Serous Ovarian Cystadenocarcinoma

Single-cell analysis reveals landscape of endometrial cancer response to estrogen and identification of early diagnostic markers

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