Transcriptome and pan-cancer system analysis identify PM2.5-induced stanniocalcin 2 as a potential prognostic and immunological biomarker for cancers.
Transcriptome and pan-cancer system analysis identify PM2.5-induced stanniocalcin 2 as a potential prognostic and immunological biomarker for cancers.
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DOI：
10.3389/fgene.2022.1077615
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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流行病学研究表明，空气污染和颗粒物（PM）与癌症的发生密切相关。然而，空气污染相关癌症的潜在预后和免疫学生物标志物缺乏。在本研究中，我们通过转录组分析证明PM2.5暴露与肺癌相关。重要的是，我们发现STC2是PM2.5调控的关键基因，PM2.5处理后，STC2在上皮细胞中的表达显著增加，并通过RT-qPCR和免疫荧光验证。Kaplan-Meier OS曲线提示STC2高表达与肺癌预后不良呈正相关。此外，我们发现STC2与多种癌症和癌症通路相关。接下来，STC2的泛癌表达图谱显示，STC2在26种人类癌症中表达不一致，癌症中的KIRP低于邻近正常组织，而在其他癌症中则显著升高。Cox回归结果显示，STC2表达与不同肿瘤的预后呈正相关或负相关。此外，STC2的表达与临床表型相关，包括年龄、性别、分期和分级。分析了STC2的突变特征，其中STC2在KIRC中变异频率最高，且扩增。同时，研究了拷贝数变异（copy number variation， CNV）对不同肿瘤类型STC2表达的影响，表明肿瘤中STC2表达与拷贝数变异（copy number variation， CNV）显著相关。此外，STC2与肿瘤异质性、肿瘤干性以及免疫细胞浸润等肿瘤免疫微环境密切相关。同时，我们分析了STC2的甲基化修饰和免疫学相关性。结果表明，STC2表达与大多数RNA甲基化基因和免疫调节剂在肿瘤中的表达呈正相关。综上所述，研究结果表明，pm2.5诱导的STC2可能是与空气污染相关的癌症的潜在预后和免疫生物标志物。
Epidemiological studies have shown that air pollution and particulate matter (PM) are closely related to the occurrence of cancer. However, the potential prognostic and immunological biomarkers for air pollution related cancers are lacking. In this study, we proved PM2.5 exposure was correlated with lung cancer through transcriptome analysis. Importantly, we identified STC2 as a key gene regulated by PM2.5, whose expression in epithelial cells was significantly increased after PM2.5 treatment and validated by using RT-qPCR and immunofluorescence. Kaplan-Meier OS curves suggested that high STC2 expression positively correlated with a poor prognosis in lung cancer. Furthermore, we discovered that STC2 was associated with multiple cancers and pathways in cancer. Next, Pan-Cancer Expression Landscape of STC2 showed that STC2 exhibited inconsistent expression across 26 types of human cancer, lower in KIRP in cancer versus adjacent normal tissues, and significantly higher in another cancers. Cox regression results suggested that STC2 expression was positively or negatively associated with prognosis in different cancers. Moreover, STC2 expression was associated with clinical phenotypes including age, gender, stage and grade. Mutation features of STC2 were also analyzed, in which the highest alteration frequency of STC2 was presented in KIRC with amplification. Meanwhile, the effects of copy number variation (CNV) on STC2 expression were investigated across various tumor types, suggesting that STC2 expression was significantly correlated with CNV in tumors. Additionally, STC2 was closely related to tumor heterogeneity, tumor stemness and tumor immune microenvironment like immune cell infiltration. In the meantime, we analyzed methylation modifications and immunological correlation of STC2. The results demonstrated that STC2 expression positively correlated with most RNA methylation genes and immunomodulators across tumors. Taken together, the findings revealed that PM2.5-induced STC2 might be a potential prognostic and immunological biomarker for cancers related to air pollution.
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影响因子：
50.3
作者：
Lin H;Kryczek I;Li S;Green MD;Ali A;Hamasha R;Wei S;Vatan L;Szeliga W;Grove S;Li X;Li J;Wang W;Yan Y;Choi JE;Li G;Bian Y;Xu Y;Zhou J;Yu J;Xia H;Wang W;Alva A;Chinnaiyan AM;Cieslik M;Zou W
通讯作者：
Zou W
影响因子：
3.8
作者：
Kong J;Yu G;Si W;Li G;Chai J;Liu Y;Liu J
通讯作者：
Liu J
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
4.6
作者：
Bonneville R;Krook MA;Kautto EA;Miya J;Wing MR;Chen HZ;Reeser JW;Yu L;Roychowdhury S
通讯作者：
Roychowdhury S
影响因子：
4.9
作者：
Li S;Huang Q;Li D;Lv L;Li Y;Wu Z
通讯作者：
Wu Z