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. 2024 Sep 28;10(22):e38702.
doi: 10.1016/j.heliyon.2024.e38702. eCollection 2024 Nov 30.

SSB expression is associated with metabolic parameters of 18F-FDG PET/CT in lung adenocarcinoma and can improve diagnostic efficiency

Zi-Yue Liu  1   2   3 , Ling-Ling Yuan  4 , Yan Gao  1 , Yu Zhang  1 , Yao-Hua Zhang  1 , Yi Yang  1 , Yu-Xuan Chen  1 , Xu-Sheng Liu  1   2   3 , Zhi-Jun Pei  5
Affiliations

SSB expression is associated with metabolic parameters of 18F-FDG PET/CT in lung adenocarcinoma and can improve diagnostic efficiency

Zi-Yue Liu et al. Heliyon. .

Abstract

Purpose: The study evaluates the expression and functional significance of the Small RNA Binding Exonuclease Protection Factor La (SSB) gene in lung adenocarcinoma (LUAD). By utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) machines, we correlated SSB gene expression with PET/CT parameters, as well as its value in LUAD diagnosis.

Methods: Fifty-five patients with LUAD underwent 18F-FDG PET/CT imaging prior to pulmonary surgery. Metabolic parameters such as maximum standardized uptake values (SUVmax) were quantitatively calculated from the 18F-FDG PET/CT imaging data. The diagnostic value was compared with that of thyroid transcription factor 1 (TTF1, the current standard-of-care). Publicly procurable datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to establish SSB gene expression patterns across diverse cancer types and specifically in LUAD, along with its associations with glycolysis and N6-methyladenosine (m6A) modification.

Results: SSB was highly expressed in LUAD compared to adjacent non-cancerous tissues. SSB additionally demonstrated superior diagnostic utility for LUAD compared to TTF1. The correlation between SSB and SUVmax as well as average standardized uptake values (SUVmean) was positive (P < 0.001), while TTF1 displayed a negative correlation with metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (P < 0.05).

Conclusion: In LUAD, SSB expression correlated with high metabolic activity (SUV) on 18F-FDG PET/CT imaging. SSB is not only an important prognostic marker for lung cancer metastases, but may also represent a novel therapeutic target.

Keywords: 18F-FDG PET/CT; Glucose; LUAD; Metabolic parameter; SSB.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Overexpression of SSB was observed in both LUAD and various types of cancer. (A) SSB expression is upregulated in various types of cancers. (B–C) Compared to normal tissues, there was upregulation of SSB expression in LUAD cancer tissues. (D) In the GSE40791 dataset, SSB was highly expressed in LUAD. (E) Differential expression of SSB mRNA was detected in the HBE normal lung cells and H1299 lung cancer cells using qPCR experiments. (F) The IHC scoring of SSB and TTF1 in both para-cancerous and cancerous tissues from patients diagnosed with LUAD were assessed using IHC. (G) IHC staining of SSB in LUAD. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
Fig. 2
Fig. 2
The correlation between the expression of SSB and clinicopathological parameters in LUAD patients. (A) The KM curves presented the survival outcomes of LUAD according to SSB expression levels. (B) LUAD ROC curve for SSB diagnosis. The SSB expression level was analyzed in relation to (C)gender, (D)smoker, (E)Pathologic stage, (F)OS event, (G–I) Pathologic T.M.N stage. ∗P < 0.05, ∗∗∗P < 0.001.
Fig. 3
Fig. 3
Diagnostic efficacy of SSB and TTF1 in LUAD. (A)The ROC curve of SSB and TTF1.
Fig. 4
Fig. 4
The expression of TTF1 and SSB in LUAD patients. (A) Two PET/CT images of patients with different SUVmax. The left image displayed an SUVmax of 19.11, while the right image showed an SUVmax of 3.13. (B) The expression of SSB and TTF1 differed between SUVmax high and low. (C) IHC staining of SSB and TTF1 in LUAD. ∗P < 0.05.
Fig. 5
Fig. 5
SSB (A) and TTF1(B) IHC scores and PET/CT metabolic parameters: SUVmax, SUVmean, TLG, and MTV were correlated.
Fig. 6
Fig. 6
SSB gene was co-expression and enriched in LUAD. (A) The volcano plot depicted genes co-expressed with SSB in the TCGA LUAD datasets. (B) The heat map showed a significant positive and negative correlation between the first 35 co-expressed genes and the expression levels of SSB in the LUAD dataset. (C–F) Enrichment analysis was conducted to elucidate the functional significance of GO terms associated with SSB co-expression genes. Furthermore, KEGG terms enrichment analyses were conducted to gain insights into the molecular pathways linked to SSB co-expression genes.
Fig. 7
Fig. 7
Correlation of SSB expression levels with m6A-related genes in LUAD. (A) m6A-gene-SSB correlation was derived from TCGA and GSE40791 dataset analysis. (B) Graph showed the correlation between four highly correlated genes with SSB. (C) SSB participated in pathways related to m6A. (D) High and low SSB groups expressed m6A-related genes differently in LUAD. (E) The Venn plot showed the expression association and differential expression of RBM15, IGF2BP3 and HNRNPA2B1 genes. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
Fig. 8
Fig. 8
Glycolysis-related genes in LUAD were correlated with SSB expression. (A) Correlation between glycolysis-related genes and SSB in TCGA and GSE40791. (B) SSB and pathways associated with glycolysis. (C) LUAD displayed differential expression of glycolytic related genes between normal and tumor groups, as well as between SSB high and low expression groups. (D) The Venn plot showed the expression association and differential expression of PGAM1. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
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