Elevated SLC2A1 Expression Correlates with Poor Prognosis in Patients with Surgically Resected Lung Adenocarcinoma: A Study Based on Immunohistochemical Analysis and Bioinformatics

Guo, Wei; Sun, Sijin; Guo, Lei; Song, Peng; Xue, Xuemin; Zhang, Hao; Zhang, Guochao; Li, Renda; Gao, Yibo; Qiu, Bin; Tan, Fengwei; Xue, Qi; Gao, Shugeng

doi:10.1089/dna.2019.5291

Cited by 18 publications

(18 citation statements)

References 34 publications

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“…Many SLCs have been reported to be aberrantly expressed in LUAD and might serve as prognostic biomarkers ( Ikeda et al, 2015 ; Lehrer and Rheinstein, 2018 ). For example, elevated expression of SLC2A1 was associated with a poorer prognosis in LUAD patients ( Guo et al, 2020 ), while increased SLC18A1 expression was associated with significantly increased survival in LUAD patients ( Lehrer and Rheinstein, 2018 ). Additionally, aberrant SLC expression contributes to accelerated cell proliferation and invasion through diverse mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, many therapeutic approaches that target SLC family members such as SLC3A2 have been examined in cancer clinical trials ( Lin et al, 2015 ). In LUAD, aberrant expression of SLC family genes has been reported to be associated with cellular proliferation and survival, and they may be useful diagnostic and prognostic biomarkers ( Ikeda et al, 2015 ; Guo et al, 2020 ; Hu et al, 2020 ; Zhou et al, 2021 ). Nevertheless, the expression profiles and clinical value of SLC family members in LUAD remain largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Zhu

Mou

et al. 2021

Front. Cell Dev. Biol.

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Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Zhu

Mou

et al. 2021

Front. Cell Dev. Biol.

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“…According to the authors, the effect of GLUT1 on the malignant phenotype of NSCLC was related to integrin β1/Src/focal adhesion kinase signaling. Guo et al 17 conducted gene set enrichment analysis and found significant enrichment of 11 hallmark pathways (including, glycolysis, G2M checkpoint, mTORC1 signaling, and hypoxia) in lung adenocarcinoma with high GLUT1 expression. Therefore, it is plausible that functional polymorphisms in GLUT1 gene may modulate the effect of GLUT1 on the prognosis of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…The following evidence supports that GLUT1 polymorphisms could be a predictive marker for adenocarcinoma as well as squamous cell carcinoma in stage III NSCLC treated with RT. Guo et al 17 found that GLUT1 was significantly overexpressed in lung adenocarcinoma tissues compared with paired normal tissues, with a higher frequency in stage III patients than in stage I or II patients (27.9% for stage I vs. 33.3% for stage II vs. 46.5% for stage III, p = 0.002); in addition, overexpression of GLUT1 was associated with worse OS in the cohort sourced from public databases and in patients who underwent R0 resection at the authors’ institution. Koh et al 23 also reported GLUT1 overexpression in 50% of surgically resected lung adenocarcinoma; GLUT1 overexpression was related to worse OS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

et al. 2021

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Background To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) who received radiotherapy. Methods Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression‐free survival (PFS) was analyzed. Results Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39–0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47–0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22–0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31–0.85, p = 0.009) compared to those with other diplotypes. Conclusions These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.

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“…Lung cancer also has high expression profile of GCNT3 (a gene regulating mucin synthesis), GOLM1(a gene coding for a Golgi transmembrane protein) and IGF2BP3 (a gene coding for a RNA binding protein), which are all positively correlated with malignant progression of lung cancer [ 50 – 53 ]. Nutrient transporter SLC2A1 and SLC7A5 both exhibit cancer-promoting potential in lung cancer [ 54 – 56 ]. TIMP1 was originally thought to be a tumor suppressor gene, since it could intensely inhibit matrix metalloproteinases (MMPs), canonical oncoproteins [ 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

A gene-based survival score for lung adenocarcinoma by multiple transcriptional datasets analysis

et al. 2020

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Background Lung adenocarcinoma (LUAD) remains a crucial factor endangering human health. Gene-based clinical predictions could be of great help for cancer intervention strategies. Here, we tried to build a gene-based survival score (SS) for LUAD via analyzing multiple transcriptional datasets. Methods We first acquired differentially expressed genes between tumors and normal tissues from intersections of four LUAD datasets. Next, survival-related genes were preliminarily unscrambled by univariate Cox regression and further filtrated by LASSO regression. Then, we applied PCA to establish a comprehensive SS based on survival-related genes. Subsequently, we applied four independent LUAD datasets to evaluate prognostic prediction of SS. Moreover, we explored associations between SS and clinicopathological features. Furthermore, we assessed independent predictive value of SS by multivariate Cox analysis and then built prognostic models based on clinical stage and SS. Finally, we performed pathway enrichments analysis and investigated immune checkpoints expression underlying SS in four datasets. Results We established a 13 gene-based SS, which could precisely predict OS and PFS of LUAD. Close relations were elicited between SS and canonical malignant indictors. Furthermore, SS could serve as an independent risk factor for OS and PFS. Besides, the predictive efficacies of prognostic models were also reasonable (C-indexes: OS, 0.7; PFS, 0.7). Finally, we demonstrated enhanced cell proliferation and immune escape might account for high clinical risk of SS. Conclusions We built a 13 gene-based SS for prognostic prediction of LUAD, which exhibited wide applicability and could contribute to LUAD management.

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Elevated SLC2A1 Expression Correlates with Poor Prognosis in Patients with Surgically Resected Lung Adenocarcinoma: A Study Based on Immunohistochemical Analysis and Bioinformatics

Cited by 18 publications

References 34 publications

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

A gene-based survival score for lung adenocarcinoma by multiple transcriptional datasets analysis

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