Transcriptome and pan-cancer system analysis identify PM2.5-induced stanniocalcin 2 as a potential prognostic and immunological biomarker for cancers

Abstract

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.

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

“…Mechanistically, long-term exposure of lung cancer cells to PM 2.5 may promote lung cancer progression through activation of the Aryl hydrocarbon receptor (AhR) and epidermal growth factor receptor (EGFR), which boosts the Serine protease pathway transmembrane 2 (TMPRSS2)-IL8 pathway. STC2 induced by PM 2.5 could be a potential immunological biomarker not only for the prognosis of lung cancer but also additional cancers related to air pollution ( Zhu et al, 2023 ). It has also been shown that human epithelial cells exposed to PM 2.5 are more susceptible to hypomethylation and transcriptional activation of several coding genes as well as microRNA, which induces modified signaling pathways related to cancer ( Heßelbach et al, 2017 ).…”

“…Renal, cardiac, liver and pulmonary fibrosis are the major causes of death, but several studies have identified common altered epigenetic regulation that could be a potential approach to target multi-organ fibrosis ( Rubio et al, 2023b ). Particularly, pulmonary fibrosis (PF) is the irreversible phenotype of all interstitial lung diseases (ILDs), characterized by progressive thickening of lung tissue that reduces gas exchange and ultimately leads to progressive hypoxemia, respiratory failure, and mortality ( Zhu et al, 2023 ). PF is an age-related ILD characterized by a failure in lung alveolar epithelial regeneration and an abnormal wound-healing response ( Chanda et al, 2019 ).…”

Pollution Characteristics of Different Components of PM2.5 in Taiyuan during 2017–2020 Wintertime and Their Toxicity Effects on HepG2 Cells

“…The liver can metabolize and decompose endogenous and exogenous substances, and lipid metabolism disorders can cause fatty liver, hepatitis and other liver diseases. Epidemiological studies have shown that PM 2.5 is not only closely related to cardiopulmonary diseases, the immune system and the nervous system [14][15][16], but also related to the incidence of liver cancer. Studies have shown that PM 2.5 and its binding compounds are deposited and metabolized in the liver, which may eventually cause liver damage [17].…”