Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma

Chen, Xiaoli; Chen, Jianing; Yan, Feng; Guan, Wei

doi:10.12659/msm.925016

Cited by 15 publications

(15 citation statements)

References 53 publications

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“…Moreover, SLC4A4 expression was shown to be higher in chronic myeloid leukemia and mucinous epithelial ovarian cancer than in adjacent normal tissue [ 14 ], suggesting that the biological processes in which SLC4A4 is involved are tumor-specific. Although SLC4A4 can indicate the prognosis of patients with colon adenocarcinoma and some other kinds of tumors [ 15 , 16 ], its significance in PCa has not been revealed.…”

Section: Introductionmentioning

confidence: 99%

SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway

et al. 2022

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Background Prostate cancer (PCa) is the second leading cause of cancer-related male deaths worldwide. The purpose of this study was to investigate the effects of homo sapiens solute carrier family 4 member 4 (SLC4A4), which encodes the electrogenic Na+/HCO3− cotransporter isoform 1 (NBCe1), in the development and progression of PCa. Methods The expression levels of SLC4A4 in PCa and normal prostate tissues were evaluated by immunohistochemistry. The SLC4A4 knockdown cell model was structured by lentiviral infection, and the knockdown efficiency was validated by RT-qPCR and Western blotting. The effects of SLC4A4 knockdown on cell proliferation, apoptosis and cycle, migration, and invasion were detected by Celigo cell counting assay and CCK-8 assay, flow cytometry analysis, wound-healing, and Transwell assay, respectively. Tumor growth in nude mice was surveyed by in vivo imaging and Ki-67 staining. Furthermore, underlying mechanism of SLC4A4 silence induced inhibition of PCa progression was explored by human phospho-kinase array. Results Our results revealed that SLC4A4 expression was up-regulated in PCa tissues and human PCa cell lines. High expression of SLC4A4 in tumor specimens was significantly correlated with disease progression. SLC4A4 knockdown inhibited cell proliferation, migration and invasion, while facilitated apoptosis, which was also confirmed in vivo. Moreover, SLC4A4 promoted PCa progression through the AKT-mediated signalling pathway. Conclusion The results of this study indicated that SLC4A4 overexpression was closely associated with the progression of PCa; SLC4A4 knockdown suppressed PCa development in vitro and in vivo. SLC4A4 acts as a tumor promotor in PCa by regulating key components of the AKT pathway and may therefore act as a potential therapeutic target for PCa treatment.

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Section: Introductionmentioning

confidence: 99%

SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway

et al. 2022

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“…In this respect, eight mRNAs (SLC4A4, MMP1, MMP3, GCG, CXCL1, CXCL3, CLCA1, and CLCA4), three lncRNAs (UCA1, LINC00449, TPT3P1) and four miRNAs (has-miR-1301, has-miR-132, has-miR-339, has-miR-497) were found to be significantly ( p < 0.01) related with poor OS of CRC patients. A majority of these hub genes were recently investigated as potential prognostic biomarkers, bioinformatically and experimentally [ 62 – 65 ]. Moreover, in our multivariate Cox model, our results suggested that out of four final lncRNAs, LINC00974 was the only lncRNA shown as a novel and potential predictor of DFS in patients with CRC, which is also reported by Gao et al in gastric carcinoma [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

An integrative transcriptome analysis reveals potential predictive, prognostic biomarkers and therapeutic targets in colorectal cancer

et al. 2022

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Background A deep understanding of potential molecular biomarkers and therapeutic targets related to the progression of colorectal cancer (CRC) from early stages to metastasis remain mostly undone. Moreover, the regulation and crosstalk among different cancer-driving molecules including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) in the transition from stage I to stage IV remain to be clarified, which is the aim of this study. Methods We carried out two separate differential expression analyses for two different sets of samples (stage-specific samples and tumor/normal samples). Then, by the means of robust dataset analysis we identified distinct lists of differently expressed genes (DEGs) for Robust Rank Aggregation (RRA) and weighted gene co-expression network analysis (WGCNA). Then, comprehensive computational systems biology analyses including mRNA-miRNA-lncRNA regulatory network, survival analysis and machine learning algorithms were also employed to achieve the aim of this study. Finally, we used clinical samples to carry out validation of a potential and novel target in CRC. Results We have identified the most significant stage-specific DEGs by combining distinct results from RRA and WGCNA. After finding stage-specific DEGs, a total number of 37 DEGs were identified to be conserved across all stages of CRC (conserved DEGs). We also found DE-miRNAs and DE-lncRNAs highly associated to these conserved DEGs. Our systems biology approach led to the identification of several potential therapeutic targets, predictive and prognostic biomarkers, of which lncRNA LINC00974 shown as an important and novel biomarker. Conclusions Findings of the present study provide new insight into CRC pathogenesis across all stages, and suggests future assessment of the functional role of lncRNA LINC00974 in the development of CRC.

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“…SLC4A4 could reverse the promoting function of Mir-222-3p on the proliferation, invasion, and migration of PTC cells ( 63 ). SLC4A4 had a lower expression in CRC than normal tissue, indicating that SLC4A4 was associated with poor prognosis ( 64 ). This study revealed that SLC4A4 may be an individual prognostic factor for CC patients and may exert a protective function in the tumorigenesis and progression of CC, which aligned well with the proposals from existing studies.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis

Yang

Lu²,

Peng³

et al. 2022

Front. Immunol.

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BackgroundColon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC.MethodsThe Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated.ResultsCALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC.ConclusionOur NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

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Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma

Cited by 15 publications

References 53 publications

SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway

SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway

An integrative transcriptome analysis reveals potential predictive, prognostic biomarkers and therapeutic targets in colorectal cancer

Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis

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