Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Abstract

Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells’ infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

Identification of a two metastasis-related prognostic signature in the process of predicting the survival of laryngeal squamous cell carcinoma

“…Some studies have found that POLR2J is overexpressed in rectal tumor organoids 20 . In addition, POLR2J is strongly positively correlated with pentapeptide-repeat domain 1 ( PTCD1 ) 21 , a mitochondrial matrix protein containing eight PPR domains 22 that regulate mitochondrial metabolism and oxidative phosphorylation. PTCD1 may be involved in immune function and immune cell infiltration, and may play a role in tumor progression and metastasis 21 .…”

“…In addition, POLR2J is strongly positively correlated with pentapeptide-repeat domain 1 ( PTCD1 ) 21 , a mitochondrial matrix protein containing eight PPR domains 22 that regulate mitochondrial metabolism and oxidative phosphorylation. PTCD1 may be involved in immune function and immune cell infiltration, and may play a role in tumor progression and metastasis 21 . Cancer elicits an immune response that solid tumors can evade, in part by establishing an immunosuppressive microenvironment.…”

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma

“…This study was conducted according to the method of Dr. Zhou et al [ 21 ]. The TCGA database was used to collect clinical data (containing 539 KIRC cases), including gender, age, grade, TNM stage, pathological stage, survival status, and survival time.…”