Alotaibi Amal, Gadekar Veerendra P, Gundla Pranav Swaroop, Mandarthi Sumana, Jayendra Nidhi, Tungekar Asna, Lavanya B V, Bhagavath Ashok Kumar, Cordero Mary Anne Wong, Pitkaniemi Janne, Niazi Shaik Kalimulla, Upadhya Raghavendra, Bepari Asmatanzeem, Hebbar Prashantha
Basic Science Department, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Mbiomics LLC, 16192 Coastal Highway, Lewes, DE, 19958, USA.
Infect Agent Cancer. 2023 Aug 28;18(1):47. doi: 10.1186/s13027-023-00525-8.
Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored.
This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis. In addition, this study deciphers population specific microbial and chemical risk factors in ESCC.
We compared the gene expression patterns of ESCC samples from six different global populations by analyzing microarray datasets. To identify DEGs, we conducted stringent quality control and employed linear modeling. We cross-compared the resulting DEG lists of each populations along with ESCC ATLAS to identify known and novel DEGs. We performed a survival analysis using The Cancer Genome Atlas Program (TCGA) data to identify potential biomarkers for ESCC diagnosis and prognosis among the novel DEGs. Finally, we performed comparative functional enrichment and toxicogenomic analysis.
Here we report 19 genes with distinct expression patterns among populations, indicating population-specific variations in ESCC. Additionally, we discovered 166 novel DEGs, such as ENDOU, SLCO1B3, KCNS3, IFI35, among others. The survival analysis identified three novel genes (CHRM3, CREG2, H2AC6) critical for ESCC survival. Notably, our findings showed that ECM-related gene ontology terms and pathways were significantly enriched among the DEGs in ESCC. We also found population-specific variations in immune response and microbial infection-related pathways which included genes enriched for HPV, Ameobiosis, Leishmaniosis, and Human Cytomegaloviruses. Our toxicogenomic analysis identified tobacco smoking as the primary risk factor and cisplatin as the main drug chemical interacting with the maximum number of DEGs across populations.
This study provides new insights into population-specific differences in gene expression patterns and their associated pathways in ESCC. Our findings suggest that changes in extracellular matrix (ECM) organization may be crucial to the development and progression of this cancer, and that environmental and genetic factors play important roles in the disease. The novel DEGs identified may serve as potential biomarkers for diagnosis, prognosis and treatment.
食管鳞状细胞癌（ESCC）预后较差，是最致命的胃肠道恶性肿瘤之一。尽管有大量转录组学研究来了解其分子基础，但人群特异性差异对该疾病的影响仍未得到探索。
本研究旨在调查从六个不同全球人群获得的ESCC样本中基因表达模式的人群特异性差异，鉴定差异表达基因（DEG）及其相关途径，并确定ESCC诊断和预后的潜在生物标志物。此外，本研究还解读了ESCC中人群特异性的微生物和化学风险因素。
我们通过分析微阵列数据集比较了来自六个不同全球人群的ESCC样本的基因表达模式。为了鉴定DEG，我们进行了严格的质量控制并采用了线性建模。我们将每个群体的所得DEG列表与ESCC ATLAS进行交叉比较，以鉴定已知和新的DEG。我们使用癌症基因组图谱计划（TCGA）数据进行生存分析，以在新的DEG中鉴定ESCC诊断和预后的潜在生物标志物。最后，我们进行了比较功能富集和毒理基因组学分析。
在此我们报告了19个在人群中具有不同表达模式的基因，表明ESCC存在人群特异性变异。此外，我们发现了166个新的DEG，如ENDOU、SLCO1B3、KCNS3、IFI35等。生存分析确定了三个对ESCC生存至关重要的新基因（CHRM3、CREG2、H2AC6）。值得注意的是，我们的研究结果表明，ESCC的DEG中与细胞外基质（ECM）相关的基因本体术语和途径显著富集。我们还发现了免疫反应和微生物感染相关途径中的人群特异性变异，其中包括富含人乳头瘤病毒、阿米巴病、利什曼病和人类巨细胞病毒的基因。我们的毒理基因组学分析确定吸烟是主要风险因素，顺铂是与各人群中最多数量的DEG相互作用的主要药物化学物质。
本研究为ESCC中基因表达模式及其相关途径的人群特异性差异提供了新见解。我们的研究结果表明，细胞外基质（ECM）组织的变化可能对这种癌症的发生和发展至关重要，并且环境和遗传因素在该疾病中起重要作用。鉴定出的新DEG可能作为诊断、预后和治疗的潜在生物标志物。
