Extracellular vesicle-encapsulated microRNA-425-derived from drug-resistant cells promotes non-small-cell lung cancer progression through DAPK1-medicated PI3K/AKT pathway.

Investigations in the area of tumor-derived extracellular vesicles (EVs) open a new horizon in developing cancer biology and its potential as cancer biomarkers. Following this prospect, we aimed to identify that the role of successfully isolated EVs from drug-resistance cells in the progression of non-small-cell lung cancer (NSCLC). P-EVs and R-EVs secreted by A549 cells and drug-resistant A549-R cells respectively were extracted and characterized. The targeting relationship between miR-425 and MED1 was verified. Cell proliferation, invasion, migration and apoptosis after treatment of P-EVs, R-EVs, miR-425 inhibitor, miR-425 mimic, pcDNA-MED1, or phosphatidylinositol-3-kinase (PI3K)/AKT inhibitor LY294002 were detected. Furthermore, xenograft tumor in nude mice was established for further confirming our in vitro findings. P-EVs and R-EVs were successfully extracted and could be internalized by A549 cells. A549-R cells and R-EVs showed higher miR-425 expression compared with A549 cells and P-EVs, respectively. miR-425 delivered by R-EVs could promote the proliferation, migration, and invasion, while inhibit apoptosis of NSCLC cells. MED1 was the target gene of miR-425. EVs-encapsulated miR-425-derived from A549-R cells could promote the progression of NSCLC in vivo through regulating DAPK1-medicated PI3K/AKT pathway. Moreover, miR-425 delivered by R-EVs promoted tumorigenesis in vivo. Taken together, the result suggested that EVs-delivered miR-425-derived from A549-R cells promoted the progression of NSCLC through regulating DAPK1-medicated PI3K/AKT signaling pathway.

Association between certain non-small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death-ligand 1 inhibition.

This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and ß-tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild-type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild-type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower ß-tubulin III expression. In addition, wild-type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD-L1 high expression. As a pilot validation, 21 wild-type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo-regimen where targeted therapy has not been a routine option. Further validation is warranted.

Metastatic EML4-ALK fusion detected by circulating DNA genotyping in an EGFR-mutated NSCLC patient and successful management by adding ALK inhibitors: a case report.

BACKGROUND: Rebiopsy is highly recommended to identify the mechanism of acquired resistance to EGFR-TKIs in advanced lung cancer. Recent advances in multiplex genotyping based on circulating tumor DNA (ctDNA) provide a strong and non-invasive alternative for detection of the resistance mechanism. CASE PRESENTATION: Here we report a multiple metastatic NSCLC patient who was detected to have pure EGFR 19 exon deletion (negative for EML4-ALK and ROS1 in both IHC-based and sequencing assay) in the primary lesion and responded to first-line and second-line EGFR-TKI treatments (erlotinib then HY-15772). At 8 months, most lesions remained well controlled except for the liver metastases which presented dramatic progression. Considering the high risk of bleeding in rebiopsy of hepatic lesions, we conducted a multiplex genomic profiling with ctDNA. Results reported coexistence of EGFR mutation and EML4-ALK gene translocation in plasma which heavily indicated that ALK was the primary reason for progression of the liver lesions. This deduction was supported by the repeated response to ALK inhibitors (crizotinib then AP26113) of the hepatic metastases. CONCLUSIONS: This is the first report of the existence of ALK rearrangement in metastatic lesions in an EGFR mutated patient. It highlighted the feasibility and advantages of using ctDNA multiplex genotyping in identifying the heterogeneity across lesions and the resistance mechanism of targeted treatments.

Nonintubated video-assisted thoracoscopic surgery under epidural anesthesia compared with conventional anesthetic option: a randomized control study.

OBJECTIVE: The purposes of this study were to evaluate the feasibility, safety, and advantages of nonintubated video-assisted thoracoscopic surgery (VATS) under epidural anesthesia, by comparing with the performance of conventional approaches. PATIENTS AND METHODS: A total of 354 patients (245 men and 109 women) were recruited in this study. The surgical procedures included bullae resection, pulmonary wedge resection, and lobectomy. The anesthetic technique (epidural vs general) was selected randomly. Patients who underwent nonintubated VATS under epidural anesthesia comprised the intervention group, and patients who received VATS under general anesthesia with double lumen tube comprised the control group. RESULTS: In total, 167 patients were included in the intervention group, and 180 patients were included in the control group. The 2 treatment groups of bullae resection showed significant differences in postoperative fasting time, duration of postoperative antibiotic use depending on the time when the white blood cells decreased to normal levels, and duration of postoperative hospital stay (P < .05). Nonintubated VATS is associated with a decreased level of inflammatory cytokines (P < .05). CONCLUSION: VATS under anesthesia with nontracheal intubation is safe and feasible, and has demonstrated advantages, including shorter postoperative fasting time, shorter duration of antibiotic use, and shorter hospital stay, compared with VATS under general anesthesia with double lumen tube.

Nonintubated uniportal video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.

OBJECTIVE: The objective of the current study was to evaluate the feasibility and safety of nonintubated uniportal video-assisted thoracoscopic surgery (VATS) for the management of primary spontaneous pneumothorax (PSP). METHODS: From November 2011 to June 2013, 32 consecutive patients with PSP were treated by nonintubated uniportal thoracoscopic bullectomy using epidural anaesthesia and sedation without endotracheal intubation. An incision 2 cm in length was made at the 6(th) intercostal space in the median axillary line. The pleural space was entered by blunt dissection for placement of a soft incision protector. Instruments were then inserted through the incision protector to perform thoracoscopic bullectomy. Data were collected within a minimum follow-up period of 10 months. RESULTS: The average time of surgery was 49.0 min (range, 33-65 min). No complications were recorded. The postoperative feeding time was 6 h. The mean postoperative chest tube drainage and hospital stay were 19.3 h and 41.6 h, respectively. The postoperative pain was mild for 30 patients (93.75%) and moderate for two patients (6.25%). No recurrences of pneumothorax were observed at follow-up. CONCLUSIONS: The initial results indicated that nonintubated uniportal video-assisted thoracoscopic operations are not only technically feasible, but may also be a safe and less invasive alternative for select patients in the management of PSP. This is the first report to include the use of a nonintubated uniportal technique in VATS for such a large number of PSP cases. Further work and development of instruments are needed to define the applications and advantages of this technique.

Thoracoscopic half carina resection and bronchial sleeve resection for central lung cancer.

BACKGROUND: The objectives of this study were to report the surgical techniques and clinical outcome of thoracoscopic half carina resection and thoracoscopic bronchial sleeve resection for central lung cancer. METHODS: Between January 2011 and November 2012, 675 patients with lung cancer underwent radical surgery by thoracoscopy, and 49 (7.3%) underwent bronchial sleeve resection. Among 49 patients, 20 (41%) received thoracoscopic bronchial sleeve lobectomy. Perioperative variables and postoperative outcomes of these cases were analyzed to evaluate the technical feasibility and safety of this operation. RESULTS: In one patient, right upper lung sleeve resection was combined with half-carinal resection and reconstruction. In another, right medial lung sleeve resection was combined with lower right dorsal segment resection. The average time of surgery was 239 ± 51 minutes (range = 142-330 minutes), and the average time of airway reconstruction was 44 ± 17 minutes (range = 22-75 minutes). The intraoperative blood loss averaged 207 ± 96 mL (range = 80-550 mL). The median postoperative hospital stay was 10 days (interquartile range = 8-12 days). Postoperatively, extubation was achieved in the recovery room without further need for mechanical ventilation. None of the patients developed anastomotic leak. Perioperative mortality was not observed. CONCLUSION: Thoracoscopic bronchial sleeve resection can be considered a feasible and safe operation for selected patients with central lung cancer. The complicated anastomosis technique of half carina resection was feasible.

Safety and feasibility of video-assisted thoracoscopic surgery for stage IIIA lung cancer.

OBJECTIVE: The current study was prospectively designed to explore the application of video-assisted thoracoscopic surgery (VATS) radical treatment for patients with stage IIIA lung cancer, with the primary endpoints being the safety and feasibility of this operation and the second endpoints being the survival and complications after the surgery. METHODS: A total of 51 patients with radiologically or mediastinoscopically confirmed stage IIIA lung cancer underwent VATS radical treatment, during which the standard pulmonary lobectomy and mediastinal lymph node dissection were performed after pre-operative assessment. The operative time, intraoperative blood loss/complications, postoperative recovery, postoperative complications, and lymph node dissection were recorded and analyzed. This study was regarded as successful if the surgical success rate reached 90% or higher. RESULTS: A total of 51 patients with non-small cell lung cancer (NSCLC) were enrolled in this study from March 2009 to February 2010. The median post-operative follow-up duration was 50.5 months. Of these 51 patients, 41 (80.4%) had N2 lymph node metastases. All patients underwent the thoracoscopic surgeries, among whom 50 (98%) received pulmonary lobectomy and mediastinal lymph node dissection completely under the thoracoscope, 6 had their incisions extended to about 6 cm due to larger tumor sizes, and 1 had his surgery performed using a 12 cm small incision for handling the adhesions between lymph nodes and blood vessels. No patient was converted to conventional open thoracotomy. No perioperative death was noted. One patient received a second surgery on the second post-operative day due to large drainage (>1,000 mL), and the postoperative recovery was satisfactory. Up to 45 patients (88.2%) did not suffer from any perioperative complication, and 6 (11.8%) experienced one or more complications. CONCLUSIONS: VATS radical treatment is a safe and feasible treatment for stage IIIA lung cancer.

Long-term survival outcomes of video-assisted thoracic surgery for patients with non-small cell lung cancer.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival. METHODS: Consecutive patients diagnosed with NSCLC referred to one institution for VATS were identified from a central database. Patients were treated by either complete-VATS or assisted-VATS, as described in previous studies. A number of baseline patient characteristics, clinicopathologic data and treatment-related factors were analyzed as potential prognostic factors on overall survival. RESULTS: Between January 2000 and December 2007, 1,139 patients with NSCLC who underwent VATS and fulfilled a set of predetermined inclusion criteria were included for analysis. The median age of the entire group was 60 years, with 791 male patients (69%). The median 5-year overall survival for Stage I, II, III and IV disease according to the recently updated TNM classification system were 72.2%, 47.5%, 29.8% and 28.6%, respectively. Female gender, TNM stage, pT status, and type of resection were found to be significant prognostic factors on multivariate analysis. CONCLUSIONS: VATS offers a viable alternative to conventional open thoracotomy for selected patients with clinically resectable NSCLC.

[18F]FAPI adds value to [18F]FDG PET/CT for diagnosing lymph node metastases in stage I-IIIA non-small cell lung cancer: a prospective study.

BACKGROUND: This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC). METHODS: From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated. RESULTS: In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients. CONCLUSION: In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions. TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).

Deciphering two decades of cellular reprogramming in cancer: A bibliometric analysis of evolving trends and research frontiers.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002-2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled "Hallmarks of Cancer: The Next Generation". A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to "extracellular vesicles," "cancer therapy," and "cellular plasticity". Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

Video-assisted thoracoscopic surgery for stage I non-small cell lung cancer: long-term survival and prognostic factors.

The purpose of this study was to evaluate the long-term outcomes of video-assisted thoracoscopic surgery (VATS) major pulmonary resection in patients with stage I non-small cell lung cancer (NSCLC). Of the 411 stage I patients, 318 (77.4 %) underwent complete VATS (c-VATS), while 89 (21.7 %) underwent assisted VATS (a-VATS). There were no intraoperative deaths. There were three deaths (0.7 %) within 30 postoperative days. The 1-, 3-, and 5-year survival rates were 95.1 % (95 % CI, 92.9­97.3 %), 83.1 % (95 % CI, 79.2­87.0 %), and 73.4 % (95 % CI, 68.1­78.7 %), respectively. Univariate analysis by log-rank test revealed that tumor-node-metastasis (TNM) stage, primary tumor (pT) status, and type of resection were statistically significant factors affecting overall survival (OS; P = 0.029, P = 0.025, and P = 0.005, respectively). Less acute TNM stage and less extensive resection were significantly predictive for longer OS by multivariate analysis as well (P = 0.024 and P = 0.006, respectively). In experienced hands, c-VATS or a-VATS can be considered as an alternative to traditional incision in patients with stage I NSCLC. Lower TNM stage and less extensive resection were significantly predictive for better OS. A prospective randomized controlled study on a larger scale is required to reach definitive conclusions regarding the efficacy of VATS relative to other techniques.

Reconstruction of the thoracic tracheal defects with portions of deepithelialized myocutaneous flaps after resection of a large tumor.

OBJECTIVE: To study the possibility of using portions of deepithelialized myocutaneous flaps to the reconstruction of thoracic tracheal defects after resection of a large tumor. METHODS: From June 2007 to June 2012, five cases of defects of the thoracic trachea were reconstructed by applying portions of deepithelialized myocutaneous flaps. The patients were 27-61 years old with 4 male cases and 1 female. The cervical trachea ranged in diameter from 4-8.5 cm with circumferences of approximately 1/3-2/5 of the bronchial circumference. RESULTS: All five patients with thoracic tracheal defects after resection of a large tumor were cured of portions of deepithelialized myocutaneous flaps, with no tracheal stricture remaining and vomica successfully eliminated. During the first 1 to 3 months after the operation, bronchoscopy showed that the tracheal lumens were smooth, and the visible skin of the musculocutaneous flaps became gray and exhibited a small amount of white discharge. CONCLUSIONS: Despite this being a small series and short follow-up, this thoracic tracheal reconstruction with portions of deepithelialized myocutaneous flaps shows encouraging preliminary results and could be an alternative to other methods for the treatment of carefully selected patients with thoracic tracheal defects.

A locally advanced colon cancer patient with Muir-Torre syndrome obtains durable response to neoadjuvant and adjuvant immunotherapy.

INTRODUCTION: Muir-Torre syndrome, presenting with cutaneous tumors and visceral malignancies, is a variant of Lynch syndrome. The development of immune checkpoint inhibitors provided novel effective treatment options for metastatic colorectal cancer patients with microsatellite instability and deficient mismatch repair. However, the use of immune checkpoint inhibitors in neoadjuvant and adjuvant settings for patients with locally advanced colorectal cancer remains undefined because of limited follow-ups in current studies. CASE PRESENTATION: In the present study, we reported a 33-year-old Muri-Torre syndrome patient with stage ⅢC (c.T4N2M0) colorectal cancer and keratoacanthoma. Microsatellite instability / deficient mismatch repair, high tumor mutation burden, and MSH2 germline mutation were identified by next-generation sequencing. Pembrolizumab monotherapy was used as neoadjuvant treatment and the patient achieved a major pathological response. After surgical resection, pembrolizumab was continuously used in an adjuvant setting for 12 months. The patient remained disease-free with a durable disease-free survival for 44 months. To our knowledge, this is the first and longest follow-up study reporting pembrolizumab as a single-agent neoadjuvant therapy for locally advanced colon cancer. CONCLUSIONS: The results demonstrate promising performance in neoadjuvant and adjuvant settings. Further studies are needed to confirm its potential usefulness as an outcome measure in clinical practice.

Efficacy of preemptive intercostal nerve block on recovery in patients undergoing video-assisted thoracic lobectomy.

BACKGROUND: Preemptive intercostal nerve block (pre-ICNB) achieves the same analgesic effects as postoperative ICNB (post-ICNB) remains unclear. This study aimed to evaluate the efficacy of preemptive ICNB on perioperative outcomes for patients undergoing video-assisted thoracic surgery (VATS). METHODS: This was a randomized, open-label study (ChiCTR2200055667) from August 1, 2021, to December 30, 2021. Eligible patients scheduled for lobectomy for lung cancer were allocated into the pre-ICNB group and the post-ICNB group. The postoperative pain evaluation, patient rehabilitation, and opioid consumption were observed. RESULTS: A total of 81 patients were included. When compared with the post-ICNB group, the pre-ICNB group had a lower proportion of hypertension comorbidity (P = 0.023), significantly lower total consumption of morphine milligram equivalents (MMEs) (P = 0.016), shorter extubation time (P = 0.019). The pre-ICNB group has similar Numeric Rating Scales (NRS) scores of dynamic pain in the post-anesthesia care unit (PACU), postoperative 6 h, 12 h, 24 h, and 48 h (P > 0.05), and had simialr scores of Bruggrmann Comfort Scale (BCS) in postoperative 6 h, 12 h, 24 and 48 h (P > 0.05). The scores of the Mini-mental state examination (MMSE) and Ramsay in the pre-ICNB group were comparable to those in the post-ICNB group, except the scores of MMSE and Ramsay in postoperative 6 h were lower (P = 0.048 and P = 0.019). The pain evaluation in the 1-month follow-up was comparable with that in the post-ICBN group (P > 0.05). CONCLUSIONS: Pre- ICNB is equally efficacious in perioperative pain management as post-ICNB, and pre-ICNB significantly reduces intra-operative opioid consumption, providing faster recovery in PACU. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Register (ChiCTR2200055667).

[Value of endobronchial ultrasound-transbronchial needle aspiration biopsy for diagnosis of PET-CT positive mediastinal lymph nodes].

OBJECTIVE: To evaluate the clinical value of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) biopsy for diagnosis of PET-CT positive mediastinal lymph nodes. METHODS: One hundred and twenty-six patients with lung cancer undergoing both PET-CT scanning and EBUS-TBNA biopsy in the First Affiliated Hospital of Guanzhou Medical College from July 2008 to August 2010 were included in this study. There were 89 male and 37 female patients with a mean age of 56.3 years (range 34 to 81 years). (18)FDG-PET was considered positive in mediastinal nodes if the PET-CT reported hypermetabolic activity consistent with malignant disease (standardized uptake value > 2.5). All of the patients were clinically followed up. RESULTS: Among the 126 patients, 185 stations of lymph nodes were punctured. The mean diameter of the nodes was 13.6 mm and the range was 6 - 23 mm. There were no procedural complications. The diagnostic accuracy, sensitivity, and specificity of EBUS-TBNA were 95.7%, 95.7%, and 100%, respectively. CONCLUSIONS: EBUS-TBNA is a minimally invasive, highly effective and accurate, practical and safe procedure for diagnosis of PET-CT positive mediastinal lymph nodes.

Pan-cancer analyses reveal the immunotherapeutic value of klotho.

Klotho (KL) was initially thought to be a typical "ageing suppressor" gene, but recent studies have suggested that KL is involved in the progression of several types of human cancer. This study aims to analyse whether the expression level of KL could impact patient prognosis, clinical parameters, and tumour immunity in different tumour patients. KL activity was utilized to determine differences between the KL transcript and KL protein. Expression levels were detected by single-sample gene enrichment analysis (GSEA). To explore the inherent mechanisms of KL in tumour immunotherapy, we investigated the possible impact of KL on the tumour microenvironment, immune processes and immune components. GO and KEGG analysis showed that KL was significantly involved in immune response, Inflammation, and calcium signaling pathway. We also found that KL was significantly correlated with multiple immunotherapeutic biomarkers (TMB, MSI, CD274, PDCD1, CTLA4 and TIGIT) in a variety of tumours. Furthermore, increased KL expression was closely associated with the non-response of anti-PD-1 immunotherapy, indicating that KL might affect the response sensitivity of tumour patients to anti-PD-1 immunotherapy. This study will provide a basis for further research on how KL regulates tumour immune cells and may lead to the development of more effective target tumour immunotherapy.

The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma.

The purpose of this research was to study the roles of chloride intracellular channel protein 1 (CLIC1) and heat shock protein 27 (HSP27) in the clinical pathology of lung adenocarcinoma and to explore whether the expression of CLIC1 and HSP27 can be used as independent factors for the prediction of recurrence and prognosis after radical resection of lung adenocarcinoma. One hundred and three paraffin sections of lung adenocarcinoma tissues were collected, and the expression of CLIC1 and HSP27 was detected in these tumors using immunohistochemistry. The correlation of the expression of these two proteins with clinicopathological parameters and prognosis was statistically analyzed. In the 103 samples, the expression of HSP27 and CLIC1 was strongly positive in 61 (59.2%) and 49 cases (47.6%), respectively. Statistical analysis showed that the expression level of HSP27 did not significantly correlate with the patient's age, sex, degree of tumor differentiation, T staging of tumors, and TNM staging of tumors (p > 0.05), whereas the expression of CLIC1 did significantly correlate with T staging of tumors (p = 0.029). Univariate analysis indicated that the patient's ECOG score, T staging, N staging, TNM staging, and CLIC1 expression correlated with prognosis (p = 0.031, 0.001, 0.011, 0.013, and <0.001, respectively). Multivariate statistical analysis showed that age, T staging, and CLIC1 expression were independent associated factors for predicting the 5-year survival rate of patients (p = 0.026, 0.004, and <0.001, respectively). Age, T staging, and CLIC1 expression significantly correlated with the overall survival of post-operative lung adenocarcinoma patients. CLIC1 may be closely associated with the occurrence and development of lung adenocarcinoma and may be used as an effective marker for predicting the prognosis of this disease.

Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the role of heat shock protein 60 (HSP60) in the clinical pathology of lung adenocarcinoma, and to explore whether the expression of HSP60 can act as an independent predictor for tumor relapse and prognosis after radical resection of lung adenocarcinoma. METHODS: Paraffin sections of lung adenocarcinoma tumor tissues were collected from 103 patients. Using immunohistochemistry, the expression levels of HSP60 in lung adenocarcinoma were detected. The correlations between HSP60 expression and clinicopathological parameters as well as prognosis were statistically analyzed. RESULTS: Of the 103 specimens, 70 cases (68.0%) showed a strongly positive expression of HSP60, five cases (4.8%) showed a negative expression, and 28 cases (27.2%) showed a weakly positive expression. The level of HSP60 expression was significantly correlated with TNM stage of the tumor (P = 0.015), and Eastern Cooperative Oncology Group (ECOG) performance status (P = 0.027). Multivariate statistical analysis showed that patient age, pathological T stage, N stage, and HSP60 expression were independent prognostic influence on disease-free survival (P = 0.008, 0.011, 0.010, and <0.001, respectively). CONCLUSIONS: HSP60 may be a good biomarker to be applied in clinic to predict the prognosis of patients with lung adenocarcinoma.

Prognostic impact of MMP-2 and MMP-9 expression in pathologic stage IA non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to assess the value of matrix metalloproteinase (MMP)-2 and MMP-9 expression and other potential prognostic factors in predicting the clinical outcome of patients after definitive surgery for pathologic stage IA non-small cell lung cancer (NSCLC). METHODS: One hundred and forty-six consecutive and non-selected patients who underwent definitive surgery for stage IA NSCLC were included in this study. Formalin-fixed paraffin-embedded specimens were stained for MMP-2 and MMP-9, which were statistically evaluated for their prognostic value and other clinicopathological parameters. RESULTS: Of the 146 patients studied, 102 (69.9%) cases were classified as having high expression for MMP-2. A total of 89 carcinomas (61.0%) had high expression for MMP-9. MMP-9 expression correlated with Eastern Cooperative Oncology Group (ECOG) performance status, pT stage, and differentiation (P = 0.005, <0.001, and <0.001, respectively). Vessel invasion, pT stage, and MMP-9 expression maintained their independent prognostic influence on overall survival (P = 0.037, <0.001, and <0.001, respectively). CONCLUSIONS: From results of our relatively large database, MMP-9 may be considered as a viable biomarker that can be used in conjunction with other prognostic factors such as vessel invasion and pT stage to predict the prognosis of patients with completely resected pathologic stage IA NSCLC.

Long-term outcome and cost-effectiveness of complete versus assisted video-assisted thoracic surgery for non-small cell lung cancer.

BACKGROUND: To compare the outcomes and costs of two methods of video-assisted thoracoscopic surgery (VATS) major pulmonary resection in patients with clinically resectable non-small cell lung cancer (NSCLC). METHODS: Between January 2000 and December 2007, 1,058 patients with proven stages I-IIIA NSCLC underwent complete VATS (c-VATS) or assisted VATS (a-VATS) major pulmonary resection together with a systematic nodal dissection. RESULTS: The study cohort consisted of 736 men and 322 women. Mean operative time was shorter for the a-VATS cohort compared with the c-VATS group (P = 0.038). Overall survival (OS) at 5 years based on Kaplan-Meier analysis was 55.3% (95%CI, 50.6-60.0%) for those who underwent c-VATS and 47.7% (95%CI, 41.2-54.2%) for those who underwent a-VATS (P = 0.404). Gender, final pathology, TNM stage, and pT status were significant predictive factors for OS according to multivariate analysis. The total cost of a-VATS lobectomy was lower than that of c-VATS lobectomy. CONCLUSIONS: c-VATS and a-VATS yield similar results in patients with clinically resectable NSCLC. a-VATS, however, may be less expensive and easier to adopt, making it a particularly attractive option for thoracic surgeons in developing countries.