RESUMEN
Malignant tumor represents a major reason for death in the world and its incidence is growing rapidly. Developing the tools for early diagnosis is possibly a promising way to offer diverse therapeutic options and promote the survival chance. Secreted phosphoprotein 1 (SPP1), also called Osteopontin (OPN), has been demonstrated overexpressed in many cancers. However, the specific role of SPP1 in prognosis, gene mutations, and changes in gene and miRNA expression in human cancers is unclear. In this report, we found SPP1 expression was higher in most of the human cancers. Based on Kaplan-Meier plotter and the PrognoScan database, we found high SPP1 expression was significantly correlated with poor survival in various cancers. Using a large dataset of colon adenocarcinoma (COAD), head and neck cancer (HNSC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, this study identified 22 common genes and 2 common miRNAs. GO, and KEGG paths analyses suggested that SPP1 correlated genes were mainly involved in positive regulation of immune cell activation and infiltration. SPP1-associated genes and miRNAs regulatory networks suggested that their interactions may play a role in the progression of four selected cancers. SPP1 showed significant positive correlation with the immunocyte and immune marker sets infiltrating degrees. All of these data provide strong evidence that SPP1 may promote tumor progress through interacting with carcinogenic genes and facilitating immune cells' infiltration in COAD, HNSC, LUAD, and LUSC.
RESUMEN
The application of cancer chronotherapy is to treat cancers based on at specific times during circadian rhythms. Previous studies have characterized the impact of circadian clock on tumorigenesis and specific immune cells. Here, by using multi-omics computation techniques, we systematically characterized the distinct roles of core circadian clock genes in thoracic cancers including lung adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. Strikingly, a wide range of core clock genes are epigenetically altered in lung adenocarcinomas and lung squamous cell carcinomas but not esophageal carcinomas. Further cancer hallmark analysis reveals that several core clock genes highly correlate with apoptosis and cell cycle such as RORA and PER2. Interestingly, our results reveal that CD4 and CD8 T cells are correlated with core clock molecules especially in lung adenocarcinomas and lung squamous cell carcinomas, indicating that chrono-immunotherapy may serve as a candidate option for future cancer management.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Relojes Circadianos/genética , Neoplasias Esofágicas/genética , Neoplasias Pulmonares/genética , Microambiente Tumoral/fisiología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Metilación de ADN , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Transcriptoma/genéticaRESUMEN
Circulating tumor cells (CTCs) are an independent prognostic marker in non-small cell lung cancer (NSCLC). CTC numbers are closely related to early diagnosis, clinical stage, therapy surveillance, and prognosis of NSCLC. We used a more efficient nano-enrichment method to detect CTCs in NSCLC patients and explored the clinical value of CTCs. The results showed that CTC numbers in stage IV cases were significantly higher than those in stage I, II or III cases. The number of CTCs in poorly-differentiated cases was significantly higher than that in well-differentiated cases. During six chemotherapy cycles, the average CTC number decreased from 5.8/7.5 ml in cycle #1 to 2.4/7.5 ml in cycle #4 and remained at almost the same level from 4 to 6 cycles. CTC numbers in patients with EGFR mutations was significantly higher than those in patients with no mutations. The average progression free survival (PFS) in the favorable group (CTC ≤ 5/7.5 ml) was 11.3 months, which was longer than that in the unfavorable group (CTC > 5/7.5 ml, 7.2 months). In conclusion, the assessment of NSCLC cannot be performed using a single CTC analysis. The clinical value is more significant in the continuous analysis of CTC data, as well as the cross-validation of other indexes and imaging results.