Candidate prognostic biomarkers and prediction models for high-grade serous ovarian cancer from urinary proteomics.

High-grade serous ovarian cancer (HGSOC) is one of the most common histologic types of ovarian cancer. The purpose of this study was to identify potential prognostic biomarkers in urine specimens from patients with HGSOC. First, 56 urine samples with information on relapse-free survival (RFS) months were collected and classified into good prognosis (RFS ≥ 12 months) and poor prognosis (RFS < 12 months) groups. Next, data-independent acquisition (DIA)-based mass spectrometry (MS) analysis was combined with MSFragger-DIA workflow to identify potential prognostic biomarkers in a discovery set (n = 31). With the aid of parallel reaction monitoring (PRM) analysis, four candidate biomarkers (ANXA1, G6PI, SPB3, and SPRR3) were finally validated in both the discovery set and an independent validation set (n = 25). Subsequent RFS and Cox regression analyses confirmed the utility of these candidate biomarkers as independent prognostic factors affecting RFS in patients with HGSOC. Regression models were constructed to predict the 12-month RFS rate, with area under the receiver operating characteristic curve (AUC) values ranging from 0.847 to 0.905. Overall, candidate prognostic biomarkers were identified in urine specimens from patients with HGSOC and prediction models for the 12-month RFS rate constructed. SIGNIFICANCE: OC is one of the leading causes of death due to gynecological malignancies. HGSOC constitutes one of the most common histologic types of OC with aggressive characteristics, accounting for the majority of advanced cases. In cases where patients with advanced HGSOC potentially face high risk of unfavorable prognosis or disease advancement within a 12-month period, intensive medical monitoring is necessary. In the era of precision cancer medicine, accurate prediction of prognosis or 12-month RFS rate is critical for distinguishing patient groups requiring heightened surveillance. Patients could significantly benefit from timely modifications to treatment regimens based on the outcomes of clinical monitoring. Urine is an ideal resource for disease surveillance purposes due to its easy accessibility. Furthermore, molecules excreted in urine are less complex and more stable than those in other liquid samples. In the current study, we identified candidate prognostic biomarkers in urine specimens from patients with HGSOC and constructed prediction models for the 12-month RFS rate.

A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis.

BACKGROUND: Ovarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), which enables cell growth, migration, and cancer stem cell maintenance, is a critical driver of disease progression and a potential intervention target of OC. However, the current OXPHOS intervention strategy mainly suppresses the activity of the electron transport chain directly and cannot effectively distinguish normal tissues from cancer tissues, resulting in serious side effects and limited efficacy. METHODS: We screened natural product libraries to investigate potential anti-OC drugs that target OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch assay, and xenograft model was applied to evaluate the anti-tumor mechanism of small molecules obtained by screening in OC. RESULTS: Gossypol acetic acid (GAA), a widely used gynecological medicine, was screened out from the drug library with the function of suppressing OXPHOS and OC progression by targeting the leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. GAA binds to LRPPRC directly and induces LRPPRC rapid degradation in a ubiquitin-independent manner. LRPPRC was overexpressed in OC, which is highly correlated with the poor outcomes of OC and could promote the malignant phenotype of OC cells in vitro and in vivo. GAA management inhibits cell growth, clonal formation, and cancer stem cell maintenance in vitro, and suppresses subcutaneous graft tumor growth in vivo. CONCLUSIONS: Our study identified a therapeutic target and provided a corresponding inhibitor for OXPHOS-based OC therapy. GAA inhibits OC progression by suppressing OXPHOS complex synthesis via targeting LRPPRC protein, supporting its potential utility as a natural therapeutic agent for ovarian cancer.

Prognostic role of multidrug resistance-associated protein 1 expression and platelet count in operable non-small cell lung cancer.

The overall survival rate of patients with non-small cell lung cancer (NSCLC) following resection remains poor due to the high rates of recurrence and metastasis. The investigation of novel biomarkers is clinically necessary to improve treatment strategies. Multidrug resistance-associated protein 1 (MRP1) and platelet count are linked to a poor prognosis in various types of cancer. However, it is unknown whether MRP1 or platelet count is a suitable prognostic indicator of NSCLC. In the present study, 427 patients with operable NSCLC were enlisted. The association of MRP1 expression and platelet count with clinical pathological factors and patient outcome was evaluated. MRP1 expression was found to be significantly associated with sex, histological type and tumor differentiation, while platelet count was significantly associated with smoking behavior, histological type and clinical stage. Platelet count was significantly higher in patients with negative MRP1 expression than in those with positive MRP1 expression. Survival analysis indicated that there was no association between MRP1 expression and disease-free survival (DFS) or overall survival (OS) time. In the patients with no lymph node metastasis, the OS time was significantly longer in patients with positive MRP1 expression than in those with negative expression. However, in the patients with lymph node metastasis, the DFS time was significantly shorter in patients with positive MRP1 expression than in those with negative expression. There was an association between the platelet count and DFS and OS times, which were significantly longer in patients with a normal platelet count than in those with thrombocytosis. In conclusion, MRP1 expression and platelet count are valuable independent prognostic biomarkers for survival in operable NSCLC.

Correlation of neuroendocrine features with prognosis of non-small cell lung cancer.

The improvement in histological diagnostic tools, including neuroendocrine markers by immunohistochemistry (IHC), has led to increased recognition of non-small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little is known regarding the prevalence and clinical implications of NE feature in patients with NSCLC. In this study, we performed IHC in a tissue microarray containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of neuroendocrine marker with pathological and clinical features of NSCLC. The result showed that NE feature in NSCLC was detectable in almost 30% of studied patients, and tumors with NE feature were significantly correlated with pathological classification, clinical stages and cell differentiation of NSCLC. Our data also revealed that NE feature indicated worse overall survival and disease free survival. Compared with mutant p53, NE markers showed more significance as for prognostic evaluation. Multi-factor COX analysis further suggested a potential clinical impact for NE feature as an independent indicator of poor prognosis for NSCLC patients.