Postoperative Non-small Cell Lung Cancer Patients Research Articles

Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients.

There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients. Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed. FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3years post-resection detected significantly more FDG-positive lesions compared to that performed after 4years. FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.

Prognostic value of visceral pleural invasion in the stage pT1-2N2M0 non-small cell lung cancer: A study based on the SEER registry

BackgroundVisceral pleural invasion (VPI) is considered an adverse prognostic factor in non-small cell lung cancer (NSCLC). However, the prognostic roles of VPI in Ⅲ/N2 NSCLC remain controversial. Therefore, this study aims to evaluate the prognostic value of VPI in patients with postoperative stage pT1-2N2M0 NSCLC. MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we screened for patients with stage T1-2N2M0 NSCLC who received surgery from 2010 to 2015. To reduce baseline differences between Non-VPI group and VPI group, two-to-one propensity score matching (PSM) was performed. Cox proportional hazards regression was used to identify factors associated with survival. Overall survival (OS) was between the Non-VPI group and the VPI+ group by the Kaplan-Meier analysis. ResultsWe identified 1374 postoperative NSCLC patients with stage pT1-2N2M0. The majority of cases (N = 1047, 76.8%) are Non-VPI patients. The factors associated with VPI+ group included white race (P < 0.0001), and adenocarcinoma (P < 0.0001).When analyzed in the total study population, VPI status remained a significant independent predictor of worse OS compared with the Non-VPI group (HR, 1.343; 95% CI, 1.083–1.665 [P=0.007]). Besides, in a subgroup analysis by VPI status, the results showed that patients without treatment exhibited a higher risk level in the Non-VPI group (P<0.0001). However, we did not find statistically significant differences among treatments in the VPI+ group (P=0.199). Mean survival time was 49.5 months (95% CI: 45.7–53.3 months) for chemotherapy alone in the Non-VPI group, compared with 41.2 months (95% CI: 35.8–46.6 months) in VPI+ groups. In both the VPI group and the non-VPI group, there is no statistical difference between adjuvant chemotherapy combined with PORT and chemotherapy alone. ConclusionThis study emphasizes that the presence of VPI is a poor prognostic factor, even in patients with Ⅲ/N2 NSCLC. As the study shows, chemotherapy significantly improved overall survival of patients with postoperative stage pT1-2N2M0 NSCLC, especially for Non-VPI patients. However, the significance of PORT is still worth further exploration.

Combined neat model for the prognosis of postoperative stage III-N2 non-small cell lung cancer.

BackgroundLung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III‐N2 non‐small cell lung cancer (NSCLC).MethodsWe enrolled 1011 patients with pathologically confirmed stage III‐N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low‐, medium‐, and high‐risk groups. Overall survival (OS), progression‐free survival (PFS), local regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log‐rank test.ResultsAbnormal CEA levels were associated with worse five‐year OS, PFS and DMFS; abnormal CYFRA21‐1 levels were associated with worse five‐year OS and LRFS; and abnormal CA125 levels were associated with worse five‐year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five‐year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001–0.004) among the three risk groups.ConclusionsThe combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes.Key pointsSignificant findings of the studySerum CEA, CYFRA21‐1, and CA125 levels can be used as prognostic factors of postoperative N2 non‐small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable.What this study addsOur model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists.

The effect of comprehensive rehabilitation program plus chemotherapy on quality of life in patients with postoperative non-small-cell lung cancer: study protocol of a multicenter randomized clinical trial

BackgroundComprehensive rehabilitation therapy based on traditional Chinese medicine (TCM) has been widely applied in various cancer treatments in China. Thus far, Chinese herbal medicine (CHM) has been shown effective in reducing the adverse effects of chemotherapy and improving the quality of life (QoL) during chemotherapy. The purpose of the present study is to compare the effects of CHM plus Liu Zi Jue (LZJ) exercises with CHM plus rehabilitation education and with placebo plus rehabilitation education in patients who have undergone complete resection for nonsmall-cell lung cancer (NSCLC) followed by postoperative adjuvant chemotherapy.Methods and designA multicenter, randomized clinical trial will be performed with 354 stage Ib–IIIa NSCLC patients in five centers in China. Patients satisfying the inclusion criteria will be randomly divided into three groups according to a 1:1:1 ratio: intervention group A (IGA), intervention group B (IGB), and control group (CG). Each group will receive adjuvant platinum-based doublet chemotherapy for a total of four cycles. IGA participants will receive chemotherapy combined with CHM and LZJ exercises, IGB participants will receive chemotherapy combined with CHM and rehabilitation education, and CG participants will receive chemotherapy combined with placebo and rehabilitation education. The herbal treatment patients will be given granules daily and LZJ exercises will be performed four times per week during chemotherapy. The primary outcome is QoL, which will be assessed with the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C43 scale in each cycle. The secondary outcomes include the 2-year disease-free survival rate, disease-free survival, TCM symptoms, tumor markers, safety, and adverse events. After treatment, the patients will be followed up every 3 months within 2 years and every 6 months after 2 years until disease recurrence and/or metastasis.DiscussionOur previous study reported that CHM in combination with chemotherapy could lower the overall incidence of adverse events but increased digestive and gastrointestinal side effects compared with chemotherapy alone in postoperative NSCLC patients. This study will lay a foundation for the effectiveness of chemotherapy with or without a comprehensive rehabilitation program for QoL in patients with postoperative NSCLC.Trial registrationClinicalTrials.gov, NCT03372694. Retrospectively registered on 17 December 2018.

Clinical significance of high expression of proliferating cell nuclear antigen in non-small cell lung cancer.

Although proliferating cell nuclear antigen (PCNA) plays an important role in tumor proliferation and its expression level is closely related to the biological activity of tumor cells, PCNA expression in non-small cell lung cancer (NSCLC) has been seldom reported. In this study, we aimed to investigate the significance of PCNA expression in NSCLC tissues. PCNA expression in NSCLC and adjacent tissues were assessed by immunohistochemistry (IHC), western blotting, and reverse transcription polymerase chain reaction. Single factor analysis was used to study the relationship between the expression of PCNA and clinicopathological features of NSCLC. Multi-factor Cox survival analysis was used to evaluate the relationship between the expression of PCNA and overall survival of postoperative NSCLC patients. The areas under the receiver operating characteristics were calculated to evaluate the value of PCNA expression level in predicting the 3-year survival of NSCLC patients. IHC analysis showed that the positive expression rates of PCNA protein in NSCLC and adjacent tissues were 91.79% (257/280) and 25.83% (31/120), respectively. Western blotting confirmed that PCNA protein level was significantly higher in NSCLC tissues than in the adjacent tissues (P < .05). Reverse transcription polymerase chain reaction showed that the positive rate of PCNA mRNA in NSCLC was 88.93% (249/280), which was significantly higher than that in adjacent tissues 29.17% (35/120) (P < .05). Both PCNA mRNA and protein levels were correlated with tumor differentiation, size, metastasis, and stage in NSCLC. Patients exhibiting higher PCNA protein expression had a significantly shorter disease-specific survival rate than the other patients. PCNA protein level and tumor pathological type, metastasis, differentiation degree, and stage were independent factors affecting the overall survival of postoperative patients. The areas under the receiver operating characteristics of PCNA mRNA for predicting the 3-year survival of NSCLC patients was 0.89 (0.79–0.98), with a sensitivity and specificity of 0.84 and 0.76, respectively. In conclusion, high PCNA protein and mRNA levels may be associated with the occurrence, development, and prognosis of NSCLC.

Weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer complicated by idiopathic interstitial pneumonias: a single-arm phase II study

Idiopathic interstitial pneumonias (IIPs) are associated with increased risk of lung cancer. In Japan, acute exaberation of IIPs induced by anticancer treatment is a critical issue. For this reason, there is limited available evidence regarding the optimal treatment approach for lung cancer patients complicated with IIPs. Our previous prospective pilot study demonstrated the safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer (NSCLC) with IIPs. The current study was conducted to confirm the results of the same combination therapy used in a larger patient population. Chemotherapy-naïve patients with advanced stage or post-operative recurrent NSCLC patients complicated by IIPs were enrolled. Patients received paclitaxel (100mg/m2) on days 1, 8, and 15, and carboplatin (AUC 5.0) once every 4weeks. Thirty-three of 35 enrolled patients were evaluable for analysis and received a median of four treatment cycles (range 1-6). Four patients (12.1%; 95% confidence interval 3.4-28.2%) had acute exacerbation (AEx)-related IIPs to the study treatment. However, no fatalities due to AEx were observed. The overall response was 69.7%. The median progression-free survival, median survival time, and 1-year survival were 6.3months, 19.8months, and 55.4%, respectively. The efficacy of carboplatin plus weekly paclitaxel treatment for advanced NSCLC patients with IIPs was comparable to that of conventional chemotherapy in advanced NSCLC patients without IIPs. Moreover, the primary endpoint was set to the frequency of treatment-related acute exacerbation, and the primary endpoint was met. These results suggest that patients with advanced NSCLC complicated by IIPs may benefit from this combination chemotherapy.

Prognostic effect of a risk index model in postoperative non-small-cell lung cancer patients.

Aim: Predicting the prognostic outcome of a single case among postoperative non-small-cell lung cancer (NSCLC) patients is difficult. We created a precise prognostic model to assess the condition and prognosis of postoperative NSCLC patients. Methods: We combined eight prognostic indicators (age, prothrombin time, international normalized ratio, globulin, albumin-to-globulin ratio, tumor diameter, number of positive lymph nodes and number of dissected lymph nodes) to construct a new risk index (RI) model. Results: The best cut-off value was -1.86 (area under the curve: 0.719). The overall survival of postoperative NSCLC patients decreased as the RI increased (p<0.001). Conclusion: This RI model can assist clinicians in screening high-risk groups and developing treatment and follow-up plans for postoperative NSCLC patients.

The prognostic effects of hyponatremia and hyperchloremia on postoperative NSCLC patients

Electrolytic disorders are common in lung cancer patients. But the association between serum electrolytes levels and survival in patients undergoing lung cancer resections for non–small-cell lung cancer (NSCLC) has been poorly investigated. A retrospective study was conducted on consecutive postoperative NSCLC patients. Pearson's test was used to determine the association between serum sodium and chlorine levels and clinical characteristics, and cox regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. We found that hyponatremia was an independent prognostic factor associated with poor prognosis in NSCLC patients undergoing complete resection (log-rank test, P = 0.004). In addition, we found that hyperchloremia predicted a poor clinical outcome in patients with non-anion-gap (log-rank test, P = 0.011), whereas it predicted a favorable clinical outcome in patients with high-anion-gap (log-rank test, P = 0.002). The serum electrolytes levels may reflect the prognosis of NSCLC patients who receive complete resection. Early detection, monitoring, and management of hyperchloremia and hyponatremia might improve patients’ prognosis.

Tai Chi Chuan in postsurgical non-small cell lung cancer patients: study protocol for a randomized controlled trial

BackgroundImpairment of exercise capacity remains a common adverse effect of non-small cell lung cancer (NSCLC) survivors after surgery. Previous research has suggested that Tai Chi Chuan (TCC) offers an exercise capacity benefit in several types of cancers. This is a randomized trial to investigate the efficacy and safety of TCC in postoperative NSCLC patients over an observation period of 3 months and a 9-month follow-up.Methods/designUsing a prospective, one center and randomized design, 120 subjects with histologically confirmed stage I–IIIA NSCLC following complete surgical resection will potentially be eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of two conditions: (1) TCC training, or (2) placebo control. The training sessions for both groups will last 60 min and take place three times a week for 3 months. The sessions will be supervised with target intensity of 60–80% of work capacity, dyspnea, and heart rate management. The primary study endpoint is peak oxygen consumption (VO2peak), and the secondary endpoints include: 6-min walk distance (6MWD), health-related quality of life (HRQoL), lung function, immunity function, and the state of depression and anxiety. All endpoints will be assessed at the baseline and postintervention (3 months). A follow-up period of 9 months will be included. The main time points for the evaluation of clinical efficacy and safety will be months 3, 6, 9, and 12 after enrollment.DiscussionThis study will assess the effect of group TCC in postsurgery NSCLC survivors on VO2peak, lung function, and other aspects. The results of this study will eventually provide clinical proof of the application of TCC as one kind of exercise training for patients across the entire NSCLC continuum, as well as information on the safety and feasibility of exercise.Trial RegistrationChinese Clinical Trial Registry: ChiCTR-IOR-15006548. Registered on 12 June 2015.

Diagnostic performance of different imaging modalities in the assessment of distant metastasis and local recurrence of tumor in patients with non-small cell lung cancer.

To compare the diagnostic performance of positron emission tomography with [18F] fluoro-2-deoxy-glucose (FDG-PET) coregistered with magnetic resonance imaging (FDG-PET/MRI), MRI with and without diffusion-weighted imaging (DWI), FDG-PET fused with computed tomography (FDG-PET/CT) with brain contrast-enhanced (CE-) MRI, and routine radiological examination for assessment of postoperative recurrence in nonsmall-cell lung cancer (NSCLC) patients. 96 consecutive postoperative NSCLC patients (52 men, 44 women; mean age 72 years) prospectively underwent whole-body 3T MRI with and without DWI; PET/CTs and routine radiological examinations consisted of CE-brain MRI, whole-body CE-CT, and bone scintigraphy. The patients were divided into a recurrence (n = 17) and a nonrecurrence (n = 79) group based on pathological and follow-up examinations. All coregistered PET/MRIs were generated by proprietary software. The probability of recurrence was visually assessed on a per-patient basis. Receiver operating characteristic analyses were used to compare the diagnostic performance of all methods. Finally, diagnostic capabilities were compared by means of McNemar's test. Areas under the curves (Azs) were significantly larger for PET/MRI and whole-body MRI with DWI (Az = 0.99) than for PET/CT (Az = 0.92, P < 0.05) and conventional radiological examination (Az = 0.91, P < 0.05). Specificity and accuracy of PET/MRI and MRI with and without DWI were significantly higher than those of PET/CT (P < 0.05) and routine radiological examination (P < 0.05). Whole-body FDG-PET/MRI and MRI with DWI were found to be more specific and accurate than FDG-PET/CT and routine radiological examinations for assessment of recurrence in NSCLC patients, although MRI with and without DWI demonstrated slightly lower sensitivity than PET/CT. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1707-1717.

Adoptive Immunotherapy in Postoperative Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BackgroundAdoptive immunotherapy (AI) has been applied in the treatment of non-small-cell lung cancer (NSCLC) patients, but the value of postoperative AI has been inconclusive largely as a result of the small number of patients included in each study. We performed a systematic review and meta-analysis to address this issue for patients with postoperative NSCLC.MethodsPubmed, Embase, Cochrane Library were searched for randomized controlled trials comparing adoptive immunotherapy with control therapies in postoperative NSCLC patients. The primary endpoint was overall survival. Hazard ratio (HR) was estimated and 95% confidence intervals (CI) were calculated using a fixed-effect model.ResultsCompared with control therapies, analyses of 4 randomized controlled trials (472 patients) showed a significant benefit of adoptive immunotherapy on survival (hazard ratio [HR] 0.61, 95% CI 0.45–0.84, p = 0.002), and a 39% reduction in the relative risk of death (no evidence of a difference between trials; p = 0.16, I² = 42%). In subgroup analyses by treatment cycles and treatment regimen, significant OS benefit was found in combination therapy of AI with chemotherapy, regardless of whether or not the treatment cycles were more than 10 cycles.ConclusionAdoptive immunotherapy has the potential to improve overall survival in postoperative NSCLC. The findings suggest this is a valid treatment option for these patients. Further randomized clinical trials are urgently needed.

Topoisomerase I expression is associated with prognosis in postoperative non-small cell lung cancer patients.

BackgroundBiomarkers may help to improve non‐small cell lung cancer (NSCLC) prognosis. However, the prognostic effect of topoisomerase I (Topo I) on NSCLC is unknown. We evaluated the clinicopathologic and prognostic significance of tumor Topo I and thymidylate synthase (TS) protein expression in postoperative NSCLC patients.MethodsOne hundred and fifteen patients with postoperative NSCLC were enrolled. Topo I and TS protein were detected in removed tumors by immunohistochemistry. The correlations between Topo I/TS protein expression and clinicopathologic characters and outcomes of patients were analyzed.ResultsIncreased expression of Topo I was found in 57 (49.6%) tumors. The largest diameter of the tumor was significantly different between patients with high and low Topo I expression (P = 0.035). TS staining showed that 35 (30.4%) carcinomas were TS positive. The level of TS expression was correlated with tumor differentiation (P = 0.037). Patients with low Topo I expression had significantly longer overall survival (OS) than those with high expression (P = 0.004). The correlation between Topo I expression and OS was demonstrated among patients with squamous cell carcinoma (P = 0.030) and patients in pathological tumor node metastasis stage I (P = 0.027). Topo I expression was positively correlated with TS expression in tumor tissue (R = 0.251, P = 0.007).ConclusionsLow Topo I expression is an independent favorable prognostic factor for longer OS in postoperative NSCLC patients, especially in squamous cell carcinoma. There is a correlation between the expression of TS and Topo I in removed tumor tissue.

Expression of epidermal growth factor receptor, carbohydrateantigen 125, and carbohydrateantigen 199 in postoperative non-small cell lung cancer patients with bone metastasis

Objective To investigate the expression of epidermal growth factor receptor (EGFR) in the tissue of non-small cell lung cancer (NSCLC), and the expression of carbohydrateantigen 125 (CA125), and carbohydrateantigen 199 (CA199) in postoperative NSCLC patients with bone metastasis and without bone metastasis, and discuss the roles of EGFR, CA125 and CA199 in postoperative NSCLC patients with bone metastasis. Methods Sixteen cases of postoperative NSCLC with bone metastasis served as the experimental group, and 16 cases of postoperative NSCLC without bone metastasis as the control group. The expression of EGFR in the lung cancer, and the serum levels of CA125 and CA199 were determined. Results The strong positive rate of EGFR was 81.2% in the experimental group. The CA125 and CA199 positive rate in the experimental group was 56.3% and 43.8% respectively. Combined detection positive rate was 81.3%. The strong positive rate of EGFR was 6.2% in the control group. The CA125 and CA199 positive rate in the control group was 0. Combined detection positive rate was 0. The serum levels of CA125 and CA199 in the experimental group were (138.05±141.06) Ku/L and (78.06±112.86) U/ml, and those in the control group were (9.94±6.50) Ku/L and (9.40±4.66) U/ml respectively. Conclusion With the high expression of EGFR, combined detection of CA125 and CA199 has certain significance in the early diagnosis of bone metastasis in postoperative NSCLC patients. Key words: Non-small cell lung cancer; Bone metastasis; Epidermal growth factor receptor; Carbohydrateantigen 125; Carbohydrateantigen 199

Adjuvant cellular immunotherapy in patients with resected primary non-small cell lung cancer

Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients ≤60 y old with positive lymph nodes.

Clinical evaluation of postoperative chemotherapy based on genetic testing in patients with stage IIIA non-small cell lung cancer.

We performed a retrospective analysis to evaluate whether a postoperative chemotherapy selection method based on four tumoral gene expression tests would improve prognosis in patients with stage IIIA non-small cell lung cancer (NSCLC) after surgery. Between January 2007 and July 2011, 148 patients with stage IIIA NSCLC underwent radical lobectomy with four cycles of adjuvant postoperative chemotherapy. Forty-five patients had tailored treatment plans based on the results of tumoral gene expression tests. The tests consisted of quantitative real-time polymerase chain reaction analyses to measure the messenger ribonucleic acid levels of the excision repair cross-complementing gene 1, ribonucleotide reductase Ml, type III β-tubulin, and thymidylate synthase genes in tumor tissues. One hundred and three patients received conventional chemotherapy. Disease responses were assessed after two cycles and every three months after the first four cycles of chemotherapy. The one and two-year survival rates and diesease-free survival (DFS) rates were recorded, and the adverse effects documented. The one and two-year DFS rates in the genetically tested group were better than those in the non-tested group, and the differences were statistically significant (P < 0.05). The two-year Kaplan-Meier DFS curve analysis results were significantly better in the genetically tested group (X(2) = 8.228, P = 0.004). The adverse effects during the treatments were not significantly different (P > 0.05) between the two groups. The chemotherapy selection method based on four tumoral gene expression tests demonstrated its feasibility to improve the efficacy of adjuvant postoperative chemotherapy and benefit stage IIIA NSCLC patients by yielding better DFS without increasing the adverse effects of chemotherapy.

The tumor suppressor miR-124 inhibits cell proliferation by targeting STAT3 and functions as a prognostic marker for postoperative NSCLC patients.

The aim of the present study was to investigate the role of miR-124 in lung cancer and identify the potential predictive value of miR-124 in postoperative non-small cell lung cancer (NSCLC) patients. We detected miR-124 expression in A549, NCL-H460 and normal lung epithelial BEAS-2E cells and showed a significantly lower expression level of miR-124 in NSCLC cells than in BEAS-2E cells. Upregulation of miR-124 expression levels in both A549 and NCL-H460 cells by transfection with miR-124 mimics suppressed cell proliferation and induced apoptosis. Further investigation revealed that miR-124 bound directly to the 3' UTR region of STAT3, thereby inhibiting STAT3 expression. In addition, miR-124 levels detected in NSCLC tissues were lower than those in adjacent normal lung tissues, while the opposite was observed for STAT3. In NSCLC, the expression levels of miR-124 and STAT3 correlated significantly with the tumor node metastases (TNM) stage, differentiation grade and lymph node metastasis, while the levels of these molecules did not differ significantly by gender, age, location, smoking index, pleural invasion or pathological type. The expression level of miR-124 was significantly associated with disease-free survival (DFS) in both positive and negative lymph node groups. Furthermore, patients with low miR-124 or high STAT3 expression generally received a worse prognosis in terms of both overall survival (OS) and DFS. In conclusion, our findings suggest that miR-124 functions as a tumor suppressor by targeting STAT3, and that miR-124 may potentially serve as a useful biomarker for the prognosis of NSCLC patients.

Relationship between the efficacy of gemcitabine/cisplatin adjuvant chemotherapy and RRM1 protein expression in postoperative NSCLC patients

The purpose of this study was to investigate the relationship between the expression of ribonucleotide reductase subunit M1 (RRM1) protein and the efficacy of gemcitabine/cisplatin (GP) adjuvant chemotherapy in postoperative non-small cell lung cancer (NSCLC) patients. A total of 68 patients with NSCLC after radical surgery were included in this study. The expression of RRM1 protein in tumor specimens was assayed by streptavidin-peroxidase (SP) immunohistochemistry retrospectively. Correlation between the expression of RRM1 protein and the efficacy of GP chemotherapy was analyzed. Disease-free survival rate was taken as the main outcome measure. Among the 68 patients, 31 cases had recurrence or metastasis. The expression rate of RRM1 was 54.4%. The 1-year and 3-year disease-free survival rates were 82.7% and 61.5% for patients with RRM1-negative expression, and 78.1% and 36.8% for patients with RRM1-posivive expression, respectively (P = 0.044). In the subgroup analysis of stage IB cases, the 1-year and 3-year disease-free survival rates were 100% and 82.3% for patients with RRM1-negative expression, and 84.5% and 24.6% for patients with RRM1-positive expression, respectively (P = 0.047). In the analysis of squamous cell carcinoma subgroup, the 1-year and 3-year disease-free survival rates were 92.3% and 83.7% for patients with RRM1-negative expression, and 83.1% and 43.9% for patients with RRM1-posivive expression, respectively (P = 0.005). Univariate analysis and multivariate analysis indicated that smoking history, pathological type, clinical stage and expression of RRM1 significantly influenced the therapeutic efficacy (P < 0.05). RRM1 protein may be a valuable predictive factor for gemcitabine/cisplatin adjuvant chemotherapy in NSCLC patients.

Combined immunophenotyping of tumor-infiltrating lymphocytes as a prognostic factor in resected patients with non-small cell lung cancer.

11125 Background: Current evidence has highlighted the potential role for tumor infiltrating lymphocytes (TILs) in determining the survival of non-small cell lung cancer (NSCLC) patients. Whilst multiple studies have investigated the prognostic role of various subtypes of TILs, data is limited on the co-expression of TILs subpopulations and its clinical relevance. Identifying immune prognostic markers may help select postoperative NSCLC patients with a poorer prognosis for treatment with immunotherapy. We aim to identify NSCLC subgroups according to combined immunophenotypes and investigate their clinical relevance. Methods: A tissue microarray was constructed from 105 cases of resected NSCLC. Immunohistochemistry for TILs with CD3, CD8, FoxP3 and Granzyme B (GZMB) Ab was performed with an autostainer. TILs were quantified using the Vectra Automated Multispectral Imaging System. Low (-) and high (+) densities of TILs were dichotomised by the medians. EGFR and KRAS mutations were determined with Sanger seq...

Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients.

The aim of the present study was to investigate the effects of a gemcitabine plus platinum (GP) regimen combined with dendritic cell-cytokine induced killer (DC-CIK) immunotherapy on the recurrence and survival rate in patients with non-small cell lung cancer (NSCLC). Patients (n=157) with stage III NSCLC that had received surgery were randomly divided into a control group and an observation group. The control group was administered with a GP regimen and the observation group received GP chemotherapy that was based on DC-CIK cell immunotherapy in addition to SC-CIK cell immunotherapy here. The two groups were followed up for 36 months and their postoperative cellular immune function, disease-free survival time, cumulative recurrence rate and cumulative survival rate was analyzed. The percentages of CD3+CD4+ T lymphocytes, natural killer cells and the CD4/CD8 ratio were identified to be significantly increased following treatment compared with those observed prior to treatment in the control and observation groups; conversely, the CD3+CD8+ T lymphocyte percentage decreased significantly (P<0.05). Furthermore, the results of the patients in the observation group were significantly better compared with the control group based on these indicators (P<0.05). The median disease-free survival time of patients in the observation group (28 months) was identified to be significantly longer than that of the control group (22 months; P<0.05), the three-year cumulative recurrence rate in the observation group (47.37%) was significantly lower than that of the control group (76.92%; P<0.05) and the three-year cumulative survival rate of the patients in the observation group (58.23%) was significantly higher than that of the control group patients (37.14%; P<0.05). In conclusion, the GP regimen combined with DC-CIK immunotherapy significantly improved the immune cell function in the postoperative NSCLC patients, in addition to reducing postoperative tumor recurrence and prolonging the survival time of patients with NSCLC.

Prognostic Significance of the Combined Score of Endothelial Expression of Nucleolin and CD31 in Surgically Resected Non-Small Cell Lung Cancer

Nucleolin is implicated to play a role in angiogenesis, a vital process in tumor growth and metastasis. However, the presence and clinical relevance of nucleolin in human non small cell lung cancer (NSCLC) remains largely unknown. In this study, we explored the expression and prognostic implication of nucleolin in surgically resected NSCLC patients. A cohort of 146 NSCLC patients who underwent surgical resection was selected for tissue microarray. In this tissue microarray, nucleolin expression was measured by immunofluorescence. Staining for CD31, a marker of endothelial cells, was performed to mark blood vessels. A Cox proportional hazards model was used to assess the prognostic significance of nucleolin. Nucleolin expression was observed in 34.2% of all patients, and 64.1% in high CD31 expression patients. The disease-free survival (DFS) was significantly shorter in patients with high nucleolin (CD31hiNCLhi) compared to patients with low tumor blood vessels (CD31loNCLlo) (5 ys of DFS 24% vs 64%, p = 0.002). Such a difference was demonstrated in the following stratified analyses: stage I (p<0.001), squamous cell carcinoma and adenosquamous cell carcinoma (p = 0.028), small tumor (<5 cm, p = 0.008), and surgery alone (p = 0.015). Multivariate analysis further revealed that nucleolin expression independently predicted for worse survival (p = 0.003). This study demonstrates that nucleolin is associated with the clinical outcomes in postoperative NSCLC patients. Thus, the expression levels of nucleolin may provide a new prognostic marker to identify patients at higher risk for treatment failure, especially in some subgroups.