Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis.

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

Clinical Value of Surgery and Establishment a Predictive Model for Breast Cancer Patients with Bone-Only Metastasis.

BACKGROUND: Whether to perform surgery on breast cancer with initial bone metastasis is heatedly debated. The aim of this study was to assess the efficacy of surgery to prolong survival time towards breast cancer patients with bone-only metastasis, and create a prognostic nomogram to predict long-term survival. METHODS: Patients diagnosed with bone-only metastatic breast cancer from 2010 to 2015 were included in this study. National Cancer Database (NCDB) was used to obtain patients' data. RESULTS: A total of 7751 patients were included for final analysis, among which 3114 (40.2%) patients had received specialized breast surgery and 4637 (59.8%) had not. Patients who had undergone surgery showed a superior overall survival (OS) compared to patients without surgery (multivariate: HR (hazard ratios) = 0.58; 95% CI (confidence interval) [0.54-0.62]; p < 0.001). Moreover, survival benefit from surgery was also true in almost all subgroups. Prognostic nomogram to individually predict patients' long-term survival rate exhibited an acceptable predictive capability, with a C-index around 0.7 both in training and validation cohorts. Clinicopathological factors included in the nomogram could discriminate patients into subgroup with different prognoses. CONCLUSIONS: Our data suggests that surgery may enhance OS in patients with initial bone-only metastatic breast cancer. Additionally, the created nomogram showed an acceptable could predict patients' long term survival.

Lipin-1 determines lung cancer cell survival and chemotherapy sensitivity by regulation of endoplasmic reticulum homeostasis and autophagy.

Cancer cells undergo comprehensive metabolic reprogramming to meet the increased requirements of energy and building blocks for proliferation. Lipin-1, a phosphatidic acid phosphatase converting phosphatidic acid (PA) to diacylglycerol (DAG), is upregulated in lung adenocarcinoma (LUAD) cell lines and tumor tissues. In this study, we reveal high lipin-1 expression is correlated with poor prognosis of patients with LUAD. Knockdown of lipin-1 decreases cell viability and proliferation in LUAD cells, whereas it has less effect on nontumorigenic lung cells. Autophagy and ER stress play important roles in tumor initiation and progression. Lipin-1 knockdown induces the initiation of autophagy while disrupts formation of autolysosome. Lipin-1 silencing induces the activation of ER stress through the IRE1α pathway. Furthermore, we demonstrate disrupted ER homeostasis contributes to the cell phenotype, and the elevated autophagy initiation is due to the ER stress in part. For the first time, we show lack of lipin-1 enhances the sensitivity of LUAD cells to cisplatin treatment. Our results suggest that lipin-1 is a potential target, alone or combined with other treatment, for lung cancer therapy.