CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients.
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ABSTRACT: Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)- and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P=0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P=0.025) together with tumour stage (P=0.006) and grade (P=0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.
Project description:BackgroundLung cancer is the leading cause of death among cancers in the world. The annual death toll due to this disease exceeds the combined deaths caused by colon, breast, prostate, and pancreatic cancers. As a result, there has been a tremendous effort to identify new biomarkers for early detection and diagnosis of lung cancer.MethodsIn this study we report the results of screening a panel of eight non-small cell lung cancer (NSCLC) cell lines originating from different subtypes of lung cancer in an attempt to identify potential biomarkers unique to this disease. We used real-time polymerase chain reaction and flow cytometry techniques to analyze the expression of ALDHA1, EpCAM, CD133, CD24, and CD38 in this panel.ResultsWe demonstrate for the first time that the majority of NSCLC cells do not express levels of CD38 that would qualify it as a new biomarker for the disease. In contrast, we found that CD24 is over-expressed in 6 out of 8 of the cell lines. The combined CD24+/CD38-/low phenotype was detected in 50% of the cell lines that are also positive for CD133 and EpCAM.ConclusionsWe report that CD24+/CD38-/low signature could potentially be used as a new biomarker for the early detection of NSCLC.
Project description:The purpose of this study was to characterize insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) expression in patients with nonsmall cell lung cancer (NSCLC).A total of 459 patients who underwent curative resection of NSCLC were studied (median follow-up duration, 4.01 years). Expression of the IR and IGF-1R protein in tumor specimens was assessed immunohistochemically using tissue microarrays.The cytoplasmic IR score was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas cytoplasmic IGF-1R score was higher in patients with SCC than those with ADC. Neither IR nor IGF-1R expression was associated with sex, smoking history, or clinical stage. Patients with positive IR or IGF-1R expression levels had poor recurrence-free (RFS) (3.8 vs 3.3 years; 3.8 vs 2.0 years, respectively), but similar overall survival (OS). Patients with high expression levels of IR and IGF-1R had shorter RFS and OS compared with those with low levels of IR and/or IGF-1R expression. Finally, a multivariate analysis revealed the impact of IR, but not of IGF-1R, as an independent predictive marker of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI], 1.001-1.010], HR for RFS, 1.005 (95% CI, 1.001-1.009), when IR score was tested as a continuous variable.Overexpression of IR predicts a poor survival among patients with NSCLC, especially those with SCC. These results might serve as future guidance to the clinical trials involving IR or IGR-1R targeting agents.
Project description:CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p=0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p=0.08). On multivariate analysis, the use of chemotherapy (p=0.0014, hazard ratio 0.069) and the CD24 overexpression (p=0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy.
Project description:We studied the rate of incidental detection of lung carcinomas and its effect on long-term survival in a nationwide cohort of patients operated for nonsmall cell lung cancer (NSCLC). All patients operated for NSCLC in Iceland during 1991-2010 were included. Demographic and clinicopathological features were compared in patients diagnosed incidentally using chest radiography or computed tomography (CT), and in those with symptomatic presentation. Multivariate analysis was used to evaluate prognostic factors. Out of 508 patients, 174 (34%) were diagnosed incidentally; in 26% of cases by chest radiography and in 8% by CT. The CT-detected tumours were significantly smaller than symptomatic tumours, diagnosed at earlier TNM (tumour, node and metastasis) stages and more often of adenocarcinoma histology. 5-year cancer-specific survival for symptomatic versus incidentally diagnosed patients detected by chest radiography and CT was 41%, 57% and 68%, respectively (p=0.003). After adjusting for stage, the hazard ratio (HR) for NSCLC mortality was significantly lower for incidental diagnosis by CT (HR 0.55, 95% CI 0.31?0.98; p=0.04) compared to incidental diagnosis by chest radiography (HR 0.95, 95% CI 0.70?1.27; p=0.71) or symptomatic diagnosis (HR 1.0). One-third of surgically treated NSCLCs were detected incidentally, with an increasing rate of incidental CT diagnosis. NSCLC patients diagnosed incidentally by CT appear to have better survival than those diagnosed incidentally by chest radiography, and particularly those who present with symptoms.
Project description:BackgroundNonsmall cell lung cancer (NSCLC) is the major determinant of overall cancer mortality worldwide. Despite progress in molecular research, current treatments offer limited benefits. Because NSCLC generates early metastasis, and this behavior requires great cell motility, herein the authors assessed the potential value of CFL1 gene (main member of the invasion/metastasis pathway) as a prognostic and predictive NSCLC biomarker.MethodsMetadata analysis of tumor tissue microarray was applied to examine expression of CFL1 in archival lung cancer samples from 111 patients, and its clinicopathologic significance was investigated. The robustness of the finding was validated using another independent data set. Finally, the authors assayed in vitro the role of CFL1 levels in tumor invasiveness and drug resistance using 6 human NSCLC cell lines with different basal degrees of CFL1 gene expression.ResultsCFL1 levels in biopsies discriminate between good and bad prognosis at early tumor stages (IA, IB, and IIA/B), where high CFL1 levels are correlated with lower overall survival rate (P<.0001). Biomarker performance was further analyzed by immunohistochemistry, hazard ratio (P<.001), and receiver-operating characteristic curve (area=0.787; P<.001). High CFL1 mRNA levels and protein content are positively correlated with cellular invasiveness (determined by Matrigel Invasion Chamber System) and resistance (2-fold increase in drug 50% growth inhibition dose) against a list of 22 alkylating agents. Hierarchical clustering analysis of the CFL1 gene network had the same robustness for stratified NSCLC patients.ConclusionsThis study indicates that the CFL1 gene and its functional gene network can be used as prognostic biomarkers for NSCLC and could also guide chemotherapeutic interventions.
Project description:PurposeThe active form of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25-D(3)), exerts antiproliferative effects in cancers, including lung adenocarcinoma (AC). CYP24A1 is overexpressed in many cancers and encodes the enzyme that catabolizes 1,25-D(3). The purpose of our study was to assess CYP24A1 as a prognostic marker and to study its relevance to antiproliferative activity of 1,25-D(3) in lung AC cells.Experimental designTumors and corresponding normal specimens from 86 patients with lung AC (stages I-III) were available. Affymetrix array data and subsequent confirmation by quantitative real time-PCR were used to determine CYP24A1 mRNA expression. A subsequent validation set of 101 lung AC was used to confirm CYP24A1 mRNA expression and its associations with clinical variables. The antiproliferative effects of 1,25-D(3) were examined using lung cancer cell lines with high as well as low expression of CYP24A1 mRNA.ResultsCYP24A1 mRNA was elevated 8- to 50-fold in lung AC (compared to normal nonneoplastic lung) and significantly higher in poorly differentiated cancers. At 5 years of follow-up, the probability of survival was 42% (high CYP24A1, n = 29) versus 81% (low CYP24A1, n = 57) (P = 0.007). The validation set of 101 tumors showed that CYP24A1 was independently prognostic of survival (multivariate Cox model adjusted for age, gender, and stage, P = 0.001). A549 cells (high CYP24A1) were more resistant to antiproliferative effects of 1,25-D(3) compared with SKLU-1 cells (low CYP24A1).ConclusionsCYP24A1 overexpression is associated with poorer survival in lung AC. This may relate to abrogation of antiproliferative effects of 1,25-D(3) in high CYP24A1 expressing lung AC.
Project description:BackgroundExpression of transglutaminase 2 (TGase 2) is related to invasion and resistance to chemotherapeutic agents in several cancer cells. However, there has been only limited clinical validation of TGase 2 as an independent prognostic marker in cancer.MethodsThe significance of TGase 2 expression as an invasive/migratory factor was addressed by in vitro assays employing down-regulation of TGase 2. TGase 2 expression as a prognostic indicator was assessed in 429 Korean patients with early-stage non-small cell lung cancer (NSCLC) by immunohistochemical staining.ResultsTGase 2 expression increased the invasive and migratory properties of NSCLC cells in vitro, which might be related to the induction of MMP-9. In the analysis of the immunohistochemical staining, TGase 2 expression in tumors was significantly correlated with recurrence in NSCLC (p = 0.005) or in the non-adenocarcinoma subtype (p = 0.031). Additionally, a multivariate analysis also showed a significant correlation between strong TGase 2 expression and shorter disease-free survival (DFS) in NSCLC (p = 0.029 and HR = 1.554) and in the non-adenocarcinoma subtype (p = 0.030 and HR = 2.184). However, the correlation in the adenocarcinoma subtype was not significant.ConclusionsTGase 2 expression was significantly correlated with recurrence and shorter DFS in NSCLC, especially in the non-adenocarcinoma subtype including squamous cell carcinoma.
Project description:Accumulating papers have demonstrated that microRNAs play an important role in the progression of lung cancer, mainly as oncogenic and tumor suppressive. Therefore, microRNAs may influence the survival of lung cancer patients. In this meta-analysis, we evaluated the role of microRNAs in affecting the overall survival in nonsmall cell lung cancer (NSCLC) patients, which may provide valuable information for the treatment of nonsmall cell lung cancer. We used keywords to retrieve literatures from online databases PUBMED, EMBASE and Web of Science and included 12 studies into our investigation according to pre-set criteria. Then, we analyzed the data with stata13.1 to evaluate the microRNAs role on the prognosis of NSCLC patients. NSCLC patients with higher microRNAs expression levels tend to show lower overall survival. HR (hazard ratio): 2.49, 95% CI (confidence interval): 1.84-3.37. Besides, both oncogenic and tumor suppressive microRNAs have an evident influence on prognosis with HR values of 2.60 (95% CI: 2.12-3.19) and 0.41 (95% CI: 0.05-0.34), respectively. microRNAs, especially from tissue, have an influence on overall survival of NSCLC patients, which indicates that microRNAs could serve as potential prognostic markers for NSCLC and may provide a treatment strategy for advanced NSCLC patients.
Project description:ObjectivesPeroxiredoxin 4 (Prx 4) is a newly emerging antioxidant protein that has been studied in several human cancers. Recently, it was revealed that Prx 4 is highly expressed in human lung cancer and is needed for the promotion of lung cancer progression in vitro. However, there are no clinical data regarding the association of Prx 4 and prognosis in lung cancer.Materials and methodsThe Prx 4 expression state as a prognostic indicator was assessed by immunohistochemical staining in 142 patients with stage II non-small cell lung cancer (NSCLC) who had undergone curative surgery between 2006 and 2010. The association between the degree of Prx 4 expression and several clinicopathologic parameters was then evaluated by statistical analyses.ResultsThe degree of Prx 4 expression was associated with histology and recurrence in the overall NSCLC patient group, with the proportion of patients with positive Prx 4 expression significantly higher for the adenocarcinoma subtype (39/70, 56%) than the squamous cell carcinoma subtype (23/72, 32%) (P = 0.004). However, when subgroup analyses according to histopathology were performed in terms of recurrence, positive Prx 4 expression was significantly correlated with higher recurrence rates (P = 0.003) and shorter disease-free survival (DFS) (P = 0.003, hazard ratio = 3.910) in patients with squamous cell carcinoma. In contrast, no meaningful relationship was observed between the level of Prx 4 expression and DFS in the adenocarcinoma subgroup.ConclusionPositive Prx 4 expression is significantly correlated with recurrence and shorter DFS in patients with early-stage lung squamous cell carcinoma.
Project description:PurposeAlthough the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM.MethodsData of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined.ResultsFifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8-68.5), 19 (3.0-62.0), and 13 (1.2-24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20-0.94)] remained significant for predicting overall survival in the multivariate analysis.ConclusionEven in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.