Abstract
Paired-like homeodomain transcription factor 1 (PITX1) is involved in numerous biological processes, including cell growth, progression, and invasion in various malignant tumors. Nevertheless, the relationship between PITX1 and kidney renal clear cell carcinoma (KIRC) remains unclear. The clinical role and functions of PITX1 were analyzed by integrating multiple open-access online datasets. Further experimental verification was performed via quantitative real-time PCR (qRT-PCR) to detect the expression of PITX1 in 10 pairs of KIRC tissues. Our results revealed that PITX1 mRNA was overexpressed in tumor tissues compared with normal tissues in the TCGA-KIRC database (p < 0.001) and numerous independent cohorts (p < 0.05). Further, high expression of PITX1 mRNA was detected in KIRC tissues compared with adjacent normal tissues in our center by qRT-PCR (N = 10, p < 0.05). Logistic regression analysis demonstrated that the PITX1 level was positively associated with KIRC patients, T and M stages, histologic grade, and pathologic stage (all p < 0.05). Survival analysis showed that upregulation of PITX1 mRNA was associated with poor overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) (all p < 0.05). Univariate/multivariate Cox hazard regression analysis revealed that PITX1 was an independent risk factor for OS in patients with KIRC (HR = 1.998, p = 0.003). Accordingly, the time-independent receiver operating characteristic (ROC) curve confirmed that PITX1 had good predictive efficacy for OS and DSS. Meanwhile, a prediction model constructed by nomogram was used to predict the OS of KIRC patients, and the calibration plot indicated this model shows high accuracy. We also revealed some downstream target genes of PITX1-related signaling pathways. Our finding suggested that high PITX1 mRNA expression may act as an independent predictive factor of poor prognosis in patients with KIRC. The prognostic model based on the nomogram would be instrumental in evaluating the survival rate in KIRC patients.
Highlights
Renal cell carcinoma (RCC) is one of the most lethal urological malignancies
A total of 539 patients from the TCGA-Kidney renal clear cell carcinoma (KIRC) cohort who presented with the required clinical characteristics were included
Previous research has reported that PITX1 expression is decreased in numerous malignant tumors, which may be attributed to enrichment of binding gene promoters and regulation gene expression as a transcription factor
Summary
Renal cell carcinoma (RCC) is one of the most lethal urological malignancies. Novel cases of RCC have skyrocketed worldwide with approximately 400,000 cases emerging each year [1]. Kidney renal clear cell carcinoma (KIRC) is considered the most aggressive histological type, accounting for 70–80% of all RCC cases [2]. Following curative treatment for localized KIRC, up to 30% of patients may experience tumor recurrence or metastasis after being considered disease-free, leading to an unsatisfactory prognosis [3]. The current conventional prognostic assessment for KIRC mainly depends on the clinical TNM stage and pathological staging. Tumor heterogeneity and complex pathogenesis often affect the predictive efficacy for the overall survival of patients with KIRC. There is an urgent need to develop sensitive and reliable prognostic models to complement the predictive outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
