Expression of KLF5 is a prognostic factor for disease-free survival and overall survival in patients with breast cancer.

PURPOSE: Kruppel-like factor (KLF5) is a cell growth mediator in various epithelial cells. Higher KLF5 increases cell growth rate and leads to transformed phenotypes. Because tumor cell proliferation is tightly associated with tumor progression, and consequently, with survival of cancer patients, we wanted to examine the prognostic value of KLF5 gene expression for patients with breast cancer. EXPERIMENTAL DESIGN: The gene expression levels of KLF5, ER, PR, HER2, and MKI67 were quantified in the tumor tissues of 90 patients with breast cancer and correlated with disease-free survival and overall survival of the patients. The correlations of gene expression between KLF5 and ER, PR, HER2, and MKI67 were analyzed. In addition, KLF5 expression was also compared with clinical data and age of patients. RESULTS: Statistically significant correlations were found between gene expression of KLF5 and both disease-free survival (univariate analysis) and overall survival (univariate and multivariate analysis). Patients with higher KLF5 expression had shorter disease-free survival and overall survival time, whereas patients with lower KLF5 expression had better survival. Moreover, KLF5 was also found to be positively correlated with HER2 and MKI67, and negatively correlated with age of the patients at diagnosis. CONCLUSION: The gene expression of KLF5 is directly correlated with cell proliferation in vivo and is a prognostic factor for patients with breast cancer. Patients with higher KLF5 expression have shorter disease-free survival and overall survival than patients with lower KLF5 expression. In addition, KLF5 has higher expression in patients ages 50 years old.     

Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival

PURPOSE: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. METHODS AND MATERIALS: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV(1)], diffusion capacity [T(lcoc)], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. RESULTS: At 3, 18, and 36 months, a significant decrease was observed for the T(lcoc) (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV(1) was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV(1) and T(lcoc) decreases were dependent on the mean lung dose. CONCLUSION: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.     

Expression of telomere-associated genes as prognostic markers for overall survival in patients with non-small cell lung cancer.

PURPOSE: Human telomeres, which are composed of long, repetitive sequences of TTAGGG and a variety of proteins, function as a protective structure capping the ends of chromosomes. Telomere dysfunction plays important roles in cancer initiation and progression. TRF1, TRF2, POT1, and RAP1 are four major telomere proteins that regulate telomere stability and telomere length. We hypothesized that the expression of these genes would have significant predictive value for cancer development and prognosis. EXPERIMENTAL DESIGN: We compared the mRNA expression level of TRF1, TRF2, POT1, and RAP1 between tumor and adjacent normal tissues from 148 patients with non-small cell lung cancer using real-time quantitative PCR. We then estimated the prognostic value of the mRNA expression of these genes in tumors. RESULTS: The expression level of TRF1 was significantly lower in tumor tissues than in adjacent normal tissues (P < 0.0001); no significant difference was found for TRF2, POT1, and RAP1. The expression of RAP1 gene in tumors was highly predictive of overall survival. In the Cox proportional hazards model, patients with higher RAP1 expression were associated with a significantly better survival [hazard ratio (HR), 0.47; 95% confidence interval (95% CI), 0.24-0.91]. This improved survival was more prominent in men (HR, 0.45; 95% CI, 0.22-0.996) and in ever smokers (HR, 0.50; 95% CI, 0.24-1.02). Kaplan-Meier survival curves showed that patients with higher RAP1 expression had significantly longer median survival than patients with lower expression (median = 51.21 versus 15.34 months, P < 0.0009). The expressions of TRF2 in tumor tissues were significantly correlated with tumor grades (P = 0.0114). CONCLUSIONS: RAP1 expression may be a useful biomarker of tumor progression and survival.     

EFR-like peptides and their receptors as prognostic factors for the survival of patients with non-small-cell lung cancer

The levels of EGFR and its ligands have been assayed in tumor and adjacent lung tissues in NSCLC patients. Both EGFR and EGF-like peptides were found in tumor more frequently than in unaltered tissue. It was shown (Kaplan-Meyer) that simultaneous expression of EGFR and its ligands in tumor and adjacent lung tissues was associated with lower overall and relapse-free survival in NSCLC patients.     

Overexpression of NUAK1 is associated with disease-free survival and overall survival in patients with gastric cancer

Transient receptor potential vanilloid 2 (TRPV2) was proved to play a crucial role in the tumor progression of various cancers. The association between the expression of TRPV2 and clinical outcome in cancer patients has not been studied yet. We aim to elucidate the role of TRPV2 in predicting prognosis of patients with esophageal squamous cell carcinoma (ESCC). Fresh frozen samples were collected immediately from 170 patients with ESCC after surgical resection from 2003 to 2008, including 45 pairs of tumor tissues and non-tumor tissues. TRPV2 expression was measured by quantitative real-time PCR. TRPV2 mRNA was over-expressed in ESCC tissues and cell lines. High expression of TRPV2 was observed more frequently in patients with advanced pT stage (P < 0.001), lymph node metastasis (P = 0.010) and advanced pathological stage (P = 0.001). Patients with high expression of TRPV2 (>44.40, n = 83) had worse 5-year disease-specific survival (40.0 vs 62.6 %, P < 0.001) and disease-free survival (38.4 vs 61.5 %, P < 0.001) than that with low expression (≤44.40, n = 87). Multivariate analysis found that the expression of TRPV2 mRNA (HR 2.19, 95 % CI 1.39–3.46, P = 0.031) and pN category (HR 2.13, 95 % CI 1.36–3.33, P = 0.001) were independent prognostic factors. Overexpression of TRPV2 mRNA was associated with poor prognosis and might serve as a novel prognostic biomarker for resected ESCC patients in early stage.     

Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer

Matrix metalloproteinase-9 is a member of the Matrix metalloproteinases (MMP) family, which is overexpressed in some solid tumor and thought to enhance the tumor invasion and metastasis ability. Our study is to investigate the association of MMP-9 expression with disease-free survival and overall survival of patients with gastric cancer. Clinical gastric cancer specimens and adjacent normal tissues from 286 patients who had not received neoadjuvant chemotherapy were investigated by immunohistochemistry assay. Staining evaluation results were analyzed statistically in relation to various clinicopathological characters, disease-free survival and overall survival. High level of MMP-9 expression was detected in gastric cancer, significantly more than in adjacent normal epithelial cells. In gastric cancer, MMP-9 was significantly positively correlated with depth of invasion, lymph node metastasis and distant metastasis. However, no correlations between MMP-9 expression and patients' age, sex, tumor location or differentiation status were detected. The disease-free survival and overall survival were significantly shorter for patients with MMP-9 positive than those with MMP-9 negative tumors. Multivariate analysis identified MMP-9 was an independent prognostic factor for both disease-free survival and overall survival. Our findings provided convincing evidence for MMP-9 as an important role in human gastric cancer recurrence and prognosis. It might also serve as a novel target for both prognostic prediction and therapeutics.     

Comparison of prognostic factors and survival among black patients and white patients treated with irradiation for non-small-cell lung cancer.

BACKGROUND: Many studies have reported differences in cancer incidence and survival between populations of Blacks and Whites. A 45% higher death rate from lung cancer for Black men and a survival duration for Black patients with lung cancer that is generally shorter than that for White patients have also been reported. PURPOSE: The purpose of this study was to evaluate whether race affects known prognostic factors for non-small-cell lung cancer in Black versus White patients. This analysis attempts to determine which prognostic factors may contribute to the reported differences in disease outcome. METHODS: We used data from 1565 patients with non-small-cell lung cancer treated in four randomized prospective trials conducted by the Radiation Therapy Oncology Group (RTOG). The data were pooled for a retrospective analysis of survival and prognostic factors by race. RESULTS: Univariate analysis showed significant differences between Blacks and Whites with regard to sex, weight loss, histology, and RTOG T stage (P < .05), but the only clinically significant difference (P < or = .01) was weight loss. Despite these findings, overall survival for Blacks and Whites did not differ significantly (P = .67). Median survival for Blacks and Whites with a Karnofsky performance status (KPS) of 90 or more was 12.1 and 11.3 months, respectively (P = .45). Survival for Blacks and Whites with a KPS of less than 90 was 7.8 and 6.8 months, respectively. Cause of death did not differ between the two races. For both races, KPS, age, sex, weight loss, and RTOG T and N stages were significant prognostic factors for survival (P < .01), but race was not a significant prognostic factor. CONCLUSION: Further studies of the differential in cancer survival for Blacks and Whites may be indicated, but greater impact may be achieved by addressing socioeconomic factors, lifestyle and occupational risk factors, health education, and access to adequate health care.     

Gene expression of PMP22 is an independent prognostic factor for disease-free and overall survival in breast cancer patients

Background  

Gene expression of peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMPs) was found to be differentially expressed in invasive and non-invasive breast cell lines in a previous study. We want to evaluate the prognostic impact of the expression of these genes on breast cancer.     

Elevated preoperative serum ICTP is a prognostic factor for overall and disease-free survival in breast cancer

The aim of this study was to evaluate the prognostic value of preoperative concentrations of the serum markers of type I collagen synthesis (PINP, PICP) and degradation (ICTP) in breast cancer. One hundred and eighty-four breast cancer patients without advanced disease were enrolled. Preoperative serum markers of type I collagen were assessed with specific radioimmunoassays. Elevated preoperative serum concentrations of ICTP (>4.9 microg/l) correlated statistically significantly with a poor prognosis for the breast cancer (P=0.0004) and shorter disease-free survival (P=0.02), and multivariate regression analysis likewise showed an elevated ICTP concentration (P=0.008), high grade (P=0.03) and high pathological stage (P=0.02) to be risk factors for poor survival. Sixty-five out of the 184 patients developed metastatic disease during the follow-up. The median follow-up time was 62 months (range 6-111 months). High ICTP (P=0.02) and large numbers of metastatic nodules (P=0.002) were prognostic factors for shorter disease-free survival in multivariate regression analysis. PINP and PICP had no significant prognostic value with respect to either overall or disease-free survival in this analysis. Our results indicate that preoperatively elevated serum ICTP is a prognostic factor in breast cancer, the measurement of which should improve the accuracy of predictions of the clinical outcome.     

Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis

Purpose

Osteopontin (OPN) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated osteopontin expression has been reported in the lung cancer tissues compared to counterpart normal tissues. This study examined whether genetic variations in the osteopontin gene are associated with survival of lung cancer patients and occurrence rate of bone metastasis.

Experimental design

Three hundred and sixty patients with stages I to IV between 2003 and 2007 were recruited in this study and same number of healthy persons were used as control. Three promoter osteopontin polymorphisms, OPN-66 T/G, -156G/GG, and -443C/T variants were genotyped using DNA from blood lymphocytes. Chi-square test and a Fisher’s exact test were used to analyze the genotype distribution among TNM stages and incidence of bone metastasis and lymph mode metastasis. Kaplan-Meier method and log-rank test were used to compare survival by different genotypes.

Results

For the variant at nt −443 (CC), there was a significant difference between the number of patients with stage IV and those with all other stages of lung cancer (p < 0.01). Patients with −443 (CC) variant had significant higher incidence of bone metastasis development compared to other genotypes. For the variant at nt −443 (CT), there was a significant difference between the number of lung cancer patients with stage III + IV and those with stage I + II (P < 0.01). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T).

Conclusion

OSTEOPONTIN −443C/T polymorphism is a potential predictive marker of survival in lung cancer patients, it is correlated with bone metastasis significantly.     

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

BackgroundWe investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC).MethodsWe included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS.ResultsGlobal health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively).ConclusionThis study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.     

Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy.

PURPOSE: Circulating cell-free DNA is present in increased amounts in the blood of cancer patients, but the clinical relevance of this phenomenon remains unclear. We conducted a clinical study to assess the value of circulating DNA as a prognostic marker in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A standard protocol for the quantification of circulating DNA by real-time polymerase chain reaction was set up and validated at two oncology units. One hundred eighty-five informed patients with NSCLC and 46 healthy controls were included in the study. DNA concentrations were determined in paired plasma and serum samples and analyzed for a relationship with leukocyte counts and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls and in patients were compared, and cutoff levels for plasma and serum DNA were determined. Patient survival was analyzed relative to baseline DNA concentrations, and the relationship between tumor responses and changes in DNA concentrations was assessed in patients receiving chemotherapy. RESULTS: We found a significant correlation between increased plasma DNA concentrations and elevated LDH levels (P = .009), advanced tumor stage (P < .003), and poor survival (P < .001). Tumor progression after chemotherapy was significantly (P = .006) associated with increasing plasma DNA concentrations. Serum DNA concentrations strongly correlated (P < .001) with leukocyte counts. CONCLUSION: Our data demonstrate that quantification of plasma DNA is an accurate technique amenable to standardization, which might complement current methods for the prediction of patient survival. This approach might be considered for evaluation in large prospective studies.     

Surgical resection of brain metastases prolongs overall survival in non-small-cell lung cancer

It remains unclear whether surgical resection of brain metastases prolongs overall survival in patients with non-small-cell lung cancer (NSCLC). A retrospective study was designed to evaluate the benefits of surgical resection for 296 patients with NSCLC and brain metastases. Patients were grouped into those who underwent craniotomy (brain surgery group) and those who did not (non-surgery group). Characteristics, survival, and EGFR mutation status were compared between the two groups. We found that the clinical characteristics were similar between the two groups. However, patients in the brain surgery group had metastases of larger diameters (3.67 cm vs. 2.06 cm, P<0.001) and a lower rate of extracranial metastasis (8.7% vs. 45.5%, P=0.001). Overall survival was significantly longer for those who underwent brain surgery (40.3 months vs. 8.4 months, P<0.001). The adjusted hazard ratio of craniotomy was 0.30 (95% confidence interval [CI], 0.15-0.62). The survival benefit of brain surgery was observed in both EGFR mutation-positive and EGFR mutation-negative sub-populations; the adjusted hazard ratios [aHRs] were 0.34 [95% CI, 0.11-1.00] and 0.26 [95% CI, 0.09-0.73] for EGFR mutation-positive and mutation-negative sub-populations, respectively. We concluded that for patients with NSCLC and brain metastases, surgical resection of brain metastases improved overall survival. This survival benefit was particularly evident in cases with large-sized metastases limited to the brain.     

Prognostic factors for disease-free and overall survival of patients with uterine carcinosarcoma

Background

Uterine carcinosarcoma (UCS) is a relatively rare and very aggressive tumor. The predictors of survival for patients with UCS have not been determined clearly yet. The aim of the present study was to investigate the possible predictors of disease-free survival (DFS) and overall survival (OS) for patients with UCS.

Methods and materials

All patients with UCS who were treated surgically at a university-based Gynecology Oncology Clinic between January 2008 and December 2014 were recruited into this retrospective cohort study. Data regarding clinical, pathologic and treatment information were obtained retrospectively from hospital records. The Kaplan–Meier method was used to calculate DFS and OS, and Cox regression analysis was performed to define the effects of risk factors on survival.

Results

A total of 88 UCS patients with a median age of 64.5 years were included in the study. Forty-seven (53.4%) patients were diagnosed with stage III disease and seven (7.9%) with stage IV disease. The median follow-up time was 16 months. Among all patients, 60 (68.1%) underwent lymphadenectomy. Optimal cytoreductive surgery was achieved in 67 (76.1%) patients. Stepwise variable selection Cox regression analysis showed that lymph node metastasis was associated with poor DFS (hazard ratio 6.524; 95% CI 2.625–16.211; P < 0.001) and OS (hazard ratio 6.993; 95% CI 2.631–18.587; P < 0.001). Subgroup analysis in both early and advanced-stage diseases revealed no significant impact of risk factors on survival.

Conclusions

Lymph node metastasis is the most significant prognostic factor associated with poor DFS and OS in UCS patients.

     

A systems pathology model for predicting overall survival in patients with refractory,advanced non-small-cell lung cancer treated with gefitinib

PurposeTo identify clinical and biometric features associated with overall survival of patients with advanced refractory non-small-cell lung cancer (NSCLC) treated with gefitinib.Experimental designOne hundred and nine diagnostic NSCLC samples were analysed for EGFR mutation status, EGFR immunohistochemistry, histologic morphometry and quantitative immunofluorescence of 15 markers. Support vector regression modelling using the concordance index was employed to predict overall survival.ResultsTumours from 4 of 87 patients (5%) contained EGFR tyrosine kinase domain mutations. A multivariate model identified ECOG performance status, and tumour morphometry, along with cyclin D1, caspase-3 activated, and phosphorylated KDR to be associated with overall survival, concordance index of 0.74 (hazard ratio (HR) 5.26, p-value 0.0002).ConclusionsSystem-based models can be used to identify a set of baseline features that are associated with reduced overall survival in patients with NSCLC treated with gefitinib. This is a preliminary study, and further analyses are required to validate the model in a randomised, controlled treatment setting.