Abstract
Indolethylamine-N-methyltransferase (INMT) is a methyltransferase downregulated in lung cancer, meningioma, and prostate cancer; however, its role and mechanism in prostate cancer remain unclear. By analyzing The Cancer Genome Atlas (TCGA)-PRAD, we found that the expression of INMT in prostate cancer was lower than that of adjacent non-cancerous prostate tissues and was significantly correlated with lymph node metastasis Gleason score, PSA expression, and survival. Combined with the GSE46602 cohorts for pathway enrichment analysis, we found that INMT was involved in regulating the MAPK, TGFβ, and Wnt signaling pathways. After overexpression of INMT in prostate cancer cell lines 22Rv1 and PC-3, we found an effect of INMT on these tumor signal pathways; overexpression of INMT inhibited the proliferation of prostate cancer cells and promoted apoptosis. Using the ESTIMATE algorithm, we found that with the increase of INMT expression, immune and stromal scores in the tumor microenvironment increased, immune response intensity increased, and tumor purity decreased. The difference in INMT expression affected the proportion of several immune cells. According to PRISM and CTRP2.0, the potential therapeutic agents associated with the INMT expression subgroup in TCGA were predicted. The area under the curve (AUC) values of 26 compounds positively correlated with the expression of INMT, while the AUC values of 14 compounds were negatively correlated with the expression of INMT. These findings suggest that INMT may affect prostate cancer’s occurrence, development, and drug sensitivity via various tumor signaling pathways and tumor microenvironments.
Highlights
Prostate cancer is the most common cancer in men; there are 1.1 million newly diagnosed cases of prostate cancer in the world every year
By analyzing The Cancer Genome Atlas (TCGA)-PRAD, we found that the RNA expression of INMT was remarkably lower in diverse stages of prostate cancer in contrast with the adjacent non-cancerous prostate tissues (Figure 1A, p < 0.001)
To confirm the difference in the transcription level of INMT in prostate cancer and adjacent non-cancerous prostate tissues analyzed in TCGA, we used western blotting to assess the levels of INMT protein in 30 pairs of prostate cancer and adjacent non-cancerous prostate tissues
Summary
Prostate cancer is the most common cancer in men; there are 1.1 million newly diagnosed cases of prostate cancer in the world every year. About 10% (307,000 cases) of male cancer-related deaths are caused by prostate cancer (Flores-Fraile et al, 2020; Woodcock et al, 2020). Between 2003 and 2017, the overall incidence rate of prostate cancer decreased; the proportion of patients diagnosed. The outcomes of prostate cancer, especially localized prostate cancer, have improved; the 5-years relative survival rate of patients with metastatic prostate cancer remained low (Liu et al, 2012; Ihle et al, 2019). The research and development of biomarkers associated with prostate cancer metastasis, including prostate-specific antigen (PSA), androgen receptor splice variant 7 (ARV7), and transforming growth factor-beta (TGFβ), might guide the early treatment decision of tumor metastasis and significantly improve outcomes (Kretschmer and Tilki, 2017; Manca et al, 2017; Bastos and Antonarakis, 2018)
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