Yang Hong, Lu Yao, Lan Weilan, Huang Bin, Lin Jiumao
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
J Cancer. 2020 Mar 26;11(12):3675-3684. doi: 10.7150/jca.36696. eCollection 2020.
: To identify potential key candidate genes, whose expression and clinical significance was further assessed in colorectal cancer (CRC). : Three original microarray datasets (GSE41328, GSE22598, and GSE23878) from NCBI-GEO were used to analyze differentially expressed genes (DEGs) in CRC. Online database analyses through Oncomine and GEIPA were performed to evaluate SLC4A4 expression and explore the prognostic merit of SLC4A4 expression, which was further confirmed by analyses from QPCR based cDNA array and IHC based tissue microarray (TMA). STRING website was used to explore the interaction between SLC4A4 with other DEGs based on the protein-protein interaction (PPI) networks. : Analysis of three original microarray datasets from GEO identified 82 shared, differentially expressed genes (28 upregulated and 54 down-regulated) in CRC tissues. Online analyses from Oncomine and GEIPA revealed lower SLC4A4 mRNA expression in CRC tissues compared to adjacent normal tissues, which were further confirmed by QPCR based cDNA array and IHC based TMA analyses on both mRNA and protein levels. Survival analyses through GEIPA and from TMA demonstrated that low SLC4A4 expression is correlated with worse overall survival among patients with CRC. Survival analysis from Kaplan-meier plotter demonstrated that low SLC4A4 expression is significantly associated with poor progression (including relapse-free survival, overall survival, distant metastasis-free survival, post-progression survival) of patients with breast cancer, lung cancer, gastric cancer, and ovarian cancer. PPI analysis found that SLC4A4 is highly correlated with various genes, including SLC9A3, SLC26A6, ENSG00000214921, SLC26A4, SLC9A3R1, and SLC9A1. : The mRNA and protein levels of SLC4A4 were decreased in CRC tissues, and low expression of SLC4A4 significantly correlated with shorter survival of CRC patients and poorer progression of patients with breast cancer, lung cancer, gastric cancer and ovarian cancer, suggesting potential role of SLC4A4 on tumor suppression and prognostic prediction in multiple malignancies including CRC.
为了鉴定潜在的关键候选基因，进一步评估其在结直肠癌（CRC）中的表达及临床意义。使用来自NCBI-GEO的三个原始微阵列数据集（GSE41328、GSE22598和GSE23878）分析CRC中差异表达基因（DEG）。通过Oncomine和GEIPA进行在线数据库分析，以评估SLC4A4的表达并探索SLC4A4表达的预后价值，基于定量PCR的cDNA阵列分析和基于免疫组化的组织微阵列（TMA）分析进一步证实了这一点。利用STRING网站基于蛋白质-蛋白质相互作用（PPI）网络探索SLC4A4与其他DEG之间的相互作用。对来自GEO的三个原始微阵列数据集进行分析，在CRC组织中鉴定出82个共享的差异表达基因（28个上调和54个下调）。Oncomine和GEIPA的在线分析显示，与相邻正常组织相比，CRC组织中SLC4A4 mRNA表达较低，基于定量PCR的cDNA阵列分析以及基于免疫组化的TMA在mRNA和蛋白质水平上的分析进一步证实了这一点。通过GEIPA和TMA进行的生存分析表明，SLC4A4低表达与CRC患者较差的总生存期相关。来自Kaplan-meier绘图仪的生存分析表明，SLC4A4低表达与乳腺癌、肺癌、胃癌和卵巢癌患者的不良进展（包括无复发生存期、总生存期、无远处转移生存期、进展后生存期）显著相关。PPI分析发现，SLC4A4与多种基因高度相关，包括SLC9A3、SLC26A6、ENSG00000214921、SLC26A,4、SLC9A3R1和SLC9A1。CRC组织中SLC4A4的mRNA和蛋白质水平降低，SLC4A4低表达与CRC患者较短的生存期以及乳腺癌、肺癌、胃癌和卵巢癌患者较差的进展显著相关，提示SLC4A4在包括CRC在内的多种恶性肿瘤的肿瘤抑制和预后预测中具有潜在作用。
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