The platelet-to-albumin ratio (PAR) was developed to evaluate inflammatory and nutritional status among patients. The primary goal of the current study was to gain insight into the prognostic role of PAR in critically ill patients with colorectal cancer (CRC). The secondary aim was to develop and verify a clinical model including PAR for the prediction of 28-day mortality. This observational, multicenter study used data from the Medical Information Mart for Intensive Care (MIMIC) IV, e-ICU databases, and Union cohort. Data from 776 critically ill patients with CRC were from the e-ICU database, 219 from the MIMC-IV database, and 135 from the Wuhan Union Hospital. Propensity score matching (PSM) analysis, along with inverse probability treatment weighting, was used to control the influence of confounding factors. Support vector machine (SVM) and LASSO Cox models were then applied to identify significant metrics associated with 28-day mortality in the test cohort. Receiver operating curve (ROC) analysis, along with sensitivity and specificity, was measured to assess the predictive performances of PAR and the survival nomogram. The threshold value for PAR was 8.6, and patients with high PAR (≥8.6) experienced higher 28-day mortality compared to those with low PAR (<8.6). ROC curve analyses revealed that the discriminative ability of PAR was better than platelet count and albumin alone. LASSO Cox regression along with SVM identified six significant metrics associated with 28-day mortality in critically ill patients with CRC, including PAR. The C-index of the critically ill CRC nomogram was 0.802 (0.744–0.859) in the e-ICU training cohort, 0.839 (0.779–0.899) in the e-ICU validation cohort, 0.787 (0.695–0.879) in the MIMIC-IV cohort, and 0.767 (0.703–0.831) in the Union cohort. PAR is a simple score that combines inflammatory and nutritional status. PAR was a reliable index to predict short-term survival outcome of critically ill patients with CRC. Moreover, a clinical nomogram incorporating PAR exhibited satisfactory performance for predicting 28-day mortality of critically ill patients with CRC.

PTOV1 is recognized to have a significant role in various human cancers, including prostate cancer. However, it remains unclear what its clinical significance and biological role are in colorectal cancer (CRC). TCGA, NCBI/GEO, and Kaplan–Meier plot database mining provided important clues into the function and clinical importance of PTOV1 in CRC. Western blotting, immunohistochemistry, and immunofluorescence were utilized to discover PTOV1 protein levels in CRC cell lines and tissues. To explore the involvement of PTOV1 in the development of CRC and the underlying mechanisms, several in-vitro and in-vivo studies were executed, such as CCK-8 assays, colony formation, transwell assays, qRT-PCR, Co-IP, GST pull-down, immunostaining, and mouse xenograft assays. It was shown that PTOV1 expression level was upregulated in the tissues and cells of human CRC. PTOV1 high-expression level was associated with short survival. ZNF449 interacted with PTOV1 and accelerated CRC development in vitro and in vivo. Through Co-IP and GST pull-down studies, the physical interaction of PTOV1/ZNF449 was demonstrated. Furthermore, PTOV1 directly bound ZNF449, and this complex synergistically promoted the transcription of MYC. In addition, the PTOV1/ZNF449 interaction was disrupted by the TAT- PTOV1 (125–283 aa) protein leading to inhibit the CRC development in a xenografted mouse model. According to these findings, PTOV1 has an essential role in CRC progression, and PTOV1/ZNF449 interaction could be a possible therapeutic target for CRC.