Expression characteristic, immune signature, and prognosis value of EFNA family identified by multi-omics integrative analysis in pan-cancer.

BACKGROUND: EphrinA (EFNA) are Eph receptor ligands that regulate various disease processes. Nonetheless, the expression characteristics of EFNAs in pan-cancer, their relationship with tumor immune microenvironment, and prognostic value landscape remain unknown. METHODS: A comprehensive landscape of EFNAs was created using various statistical data extracted from 33 cancers. Subsequently, we identified differential expression, genetic variations, potential function enrichment, tumor immune-related analysis, and drug sensitivity. Further, we investigated the clinical features and diagnostic prognostic value of EFNAs. RT-qPCR, western blot and immunohistochemistry (IHC) were used to validate the expression level and significant clinical value of EFNA5 in lung adenocarcinoma cell lines and tissues. RESULTS: EFNAs were highly mutated in various cancers. Genomic and epigenetic alterations of EFNAs were observed in various tumors, where an oncogenic mutation in specific cancer types potentially affected EFNA expression. Moreover, tumor-derived EFNAs were significantly related to the tumor immune microenvironment, suggesting that they are promising therapeutic targets. The majority of EFNA family genes were significantly linked to patient prognosis. Eventually, EFNA5 was an independent prognostic factor in lung adenocarcinoma. CONCLUSION: In summary, EFNAs are crucial in tumor immune regulation, and EFNA5 is a prognostic marker in lung adenocarcinoma. Our findings provide new insights into EFNAs from a bioinformatics standpoint and highlight the significance of EFNAs in cancer diagnosis and treatment.

Characterization of the prognostic and diagnostic values of ALKBH family members in non-small cell lung cancer.

BACKGROUND: AlkB homolog (ALKBH) family genes have been known to play a crucial role in the development of several types of cancers. Nevertheless, the prognostic and diagnostic values of ALKBH family members have not been systematically investigated in non-small cell lung cancer (NSCLC). METHODS: The mRNA expression, genomic mutations, and biological functions of ALKBH family genes in NSCLC were evaluated using ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioPortal, Metascape, and SurvivalMeth. ALKBH2 expression and associated clinicopathological features were analyzed in LUAD tissues using immunohistochemistry (IHC). RESULTS: The mRNA levels of ALKBH1/2/4/6 were significantly upregulated in NSCLC patients, while those of ALKBH7 and FTO were downregulated. Also, a higher expression of ALKBH2/4/6 correlated with poor overall survival (OS), first-progression survival (FPS), and post-progression survival (PPS). ALKBH3/8 and FTO were upregulated and related to better OS, FPS, and PPS. ALKBH2/4/6 and FTO showed a higher diagnostic value in differentiating NSCLC patients from healthy individuals. Furthermore, the ALKBH family mutation rate was as high as 57% in lung adenocarcinoma (LUAD) patients and mutations in ALKBHs were related to poor OS. ALKBH family genes were also involved in universal DNA methylation in NSCLC. Finally, it was confirmed using tissues microarray that ALKBH2 shows a high expression and has a great diagnosis value in LUAD. CONCLUSIONS: Firstly, our results provided prognostic and diagnostic values of ALKBH family genes in NSCLC at both the DNA and RNA levels. Secondly, ALKBH2 is a potential novel diagnostic biomarker for LUAD.

Clinical Associations of Preoperative and Postoperative Serum CEA and Lung Cancer Outcome.

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis. Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression. Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p < 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p < 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p < 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5-2.7, p < 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9-1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4-2.7, p < 0.001). Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.