Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial.

BACKGROUND: Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRASG12C inhibitor, has shown promising antitumour activity in patients with KRASG12C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG12C-mutated NSCLC. METHODS: This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRASG12C-mutated NSCLC who had previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors from 43 hospitals in China. Participants received 600 mg garsorasib orally twice per day. Tumour assessments were performed at baseline, at the end of every two cycles (of 21 days) for the first eight cycles, and at the end of every three cycles thereafter. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC) following the guidelines in Response Evaluation Criteria in Solid Tumours, version 1.1. Efficacy and safety were assessed in all patients who received at least one dose of garsorasib. This trial is registered at ClinicalTrials.gov, NCT05383898, and is active but no longer recruiting. FINDINGS: From June 17, 2022, to May 17, 2023, of 225 patients screened for eligibility, 123 patients were enrolled and treated with garsorasib. Of these 123 participants, the median age was 64 years (IQR 59-68), 108 (88%) were male and 15 (12%) were female. At data cutoff (Nov 17, 2023), the median follow-up duration was 7·9 months (IQR 6·3-10·4), and 82 (67%) of 123 patients had discontinued treatment. The IRC-confirmed ORR was 50% (61 of 123 patients; 95% CI 41-59). 117 (95%) of 123 patients reported treatment-related adverse events, with 61 (50%) experiencing grade 3 or higher events. The most common types of adverse events of grade 3 or higher associated with garsorasib were hepatic and gastrointestinal events, including increased liver enzymes, such as aspartate aminotransferase (21 [17%] of 123 participants), alanine aminotransferase (19 [15%] of 123 participants), and gamma-glutamyltransferase (28 [23%] of 123 participants); nausea (2 [2%] of 123 participants); and vomiting (2 [2%] of 123 participants). No new safety signals were identified, and most of the adverse events were well managed. INTERPRETATION: The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population. FUNDING: InventisBio.

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.

Importance: Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. Objective: To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. Design, Setting, and Participants: This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Interventions: Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. Main Outcomes and Measures: The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Results: Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Conclusions and Relevance: Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT04063163.

Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter, Single-Arm, Open-Label Study.

INTRODUCTION: Befotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy. METHODS: This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156. RESULTS: A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data cutoff (August 15, 2021), independent review committee-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median independent review committee-assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0-not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%-78.2%) and 55.9% (95% CI: 37.9%-72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6-NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively. CONCLUSIONS: Befotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

[Pre-Transfusion Testing and Transfusion Strategy in Patients with Multiple Myeloma after Daratumumab Treatment].

OBJECTIVE: To investigate the procedure of pre-transfusion testing and transfusion strategy of patients with multiple myeloma (MM) treated by daratumumab (DarA). METHODS: The blood samples of MM patients before and after DarA treatment from the Fifth Affiliated Hospital of Sun Yat-sen University were collected, and the ABO/Rh blood group antigen identification and DAT test results were compared. The results of antibody screening and cross matching of the patients before and after inactivation of red blood cells with 0.2 mol/L dithiothreitol (DTT) were compared and analyzed. RESULTS: ABO/Rh blood group antigen typing showed no affecting in patients after treated by DarA; the result of DAT test showed negative. Irregular antibody screening showed that all the three cells(Ⅰ, Ⅱ and Ⅲ) were positive(1+~2+) and the self-control was negative. By microcolumn agglutination method, the main side of the multi-bag of blood showed no matched, while the secondary side showed all identical. After treated by DTT solution, the cross matching results in reagent red blood cells and the red blood cells of blood donors were both consistent, and the irregular antibody screening was negative. The K(+)O type erythrocytes used in parallel control were transformed into K(-)O type erythrocytes after DTT treatment. However, there was no significant changes in E(+) O type erythrocytes before and after DTT treatment. There was no condensation on the primary and secondary side of the condensed amine method. The primary and secondary sides of blood matching by saline method showed negative. CONCLUSION: After treated by DarA, cross matching results from microcolumn agglutination method can be interfered by the residual drug antibody in MM patients, while the interference was eliminated in the presence of 0.2 mol/L DTT solution. However, no disturbance was observed when using condensed amine method or saline method. Therefore, corresponding transfusion procedures should be selected according to the emergency degree of blood transfusion to ensure the safety and timeliness of blood transfusion.

Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial.

BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

Role of HPV status and PD-L1 expression in prognosis of laryngeal squamous cell carcinoma.

PURPOSE: Human papillomavirus (HPV) infection has been recognized as a cause of head and neck squamous cell carcinomas (HNSCC). Laryngeal squamous cell carcinoma (LSCC) is one of the most common pathologic types of HNSCC. Clinical trials show that there are differences in response to immunotherapy according to HPV status. It was reported that a high level of programmed cell death-ligand 1 (PD-L1) is correlated with better survival in HPV-positive head and neck cancer. In this study, we investigated the expression of PD-L1 in HPV-positive and HPV-negative LSCC to determine its prevalence and prognostic value. METHODS: 52 cases of LSCC were collected from Tangshan Head and Neck Disease Pathology Research Base. PCR-reverse dot blot hybridization and RNAscope in situ hybridization were used to detect HPV status. PD-L1 expression was evaluated by immunohistochemistry and all cases were followed up for survival. SPSS24.0 was used for data entry and statistical analysis. Kaplan-Meier method and Log-rank time series analysis were used for single factor analysis. Multivariate analysis was performed using Cox proportional hazard regression model, and HR and 95% CI were calculated. RESULTS: Of the 52 LSCC patients, 32.7% (17/52) were HPV-positive by RNAscope in situ hybridization, and 51.9% (27/52) of patients were positive for PD-L1 expression by immunohistochemistry. Regression analysis showed that with a median follow-up period of 69 months, smoking and late stage were associated with poor overall survival (OS), whereas HPV positivity and PD-L1 expression showed a better overall survival outcome. CONCLUSION: Smoking status, tumor stage, HPV status, and PD-L1 expression in tumor cells may represent useful prognostic biomarkers in patients with LSCC.

High risk HPV detection by RNAscope in situ hybridization combined with Cdc2 protein expression by immunohistochemistry for prognosis of oropharyngeal squamous cell carcinoma.

High risk human papillomavirus (HPV) infection is related to the development of head and neck squamous cell carcinoma (HNSCC). Oropharyngeal squamous cell carcinoma (OPSCC) is a common type of HNSCC, and its incidence has increased significantly in recent years. In this study, high risk HPV, the expression of P53, P21, and Cdc2 in OPSCC tissues was detected and the prognostic factors and clinical value of OPSCC were discussed. According to the WHO classification and diagnosis standard for head and neck tumors (2017 Edition), 49 OPSCC cases with complete clinical data were collected from Tangshan Head and Neck Disease Pathology Research Base from January 1, 2012 to December 31, 2018. The E6 and E7 mRNA of HPV 16 and HPV 18 were detected by RNAscope in situ hybridization. The expression of P53, P21, and Cdc2 protein was observed by SP immunohistochemical method and all cases were followed up for survival. Median survival time was analyzed by Kaplan-Meier method. The Log-rank test was used for single factor analysis and Cox regression model was used to analyze multiple prognostic factors. In 49 OPSCC cases the median age was 53 years; 14 were HPV-DNA positive (14/49, 28.6%) while 35 were negative (35/49, 71.4%). E6, E7 mRNA test showed that 20 cases (20/49, 40.8%) were positive for HPV-16. Among them 11 cases were positive for HPV-16 DNA. 2 cases were positive for HPV-18 mRNA (2/49, 4.08%). 27 cases were negative for mRNA16 and 18 (27/49, 55.1%). The prevalence of HPV was 68.8% (11/16) in the non-smoking group, which was higher than that of the smoking group (10/33, 33.3%), (χ2=5.463, P=0.019). There was no significant correlation between HPV detection and gender, age, drinking, tumor differentiation degree, and clinical stage (P > 0.05). The expression rates of P53, P21, and Cdc2 in OPSCC tissues were 63.3% (31/49), 65.3% (32/49), and 67.3% (33/49), respectively. There was no significant correlation between expression of all the three proteins and gender, age, HPV, smoking, drinking, tumor differentiation, and clinical stage (P > 0.05). Cox multifactor regression analysis showed that HPV (HR=0.275, 95% CI: 0.146-0.517), tumor differentiation (HR=1.751, 95% CI: 1.231-2.492), stage (HR=3.268, 95% CI: 1.758-6.074) and expression of Cdc2 protein (HR=1.804, 95% CI: 0.990-3.286) were related to the survival time of patients (P < 0.05). Our findings support that most of the HPV-positive OPSSC patients were non-smokers. The patients with negative HPV, low differentiation, late stage, and Cdc2 positive expression have poor prognosis and need to be followed up.

Ginsenoside Rg1 inhibits apoptosis by increasing autophagy via the AMPK/mTOR signaling in serum deprivation macrophages.

Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and cerebral-vascular diseases because of its unique therapeutic properties. However, the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not been fully explored. This study sought to determine the precise molecular mechanisms on how Rg1 might be involved in regulating apoptosis in serum deprivation-induced Raw264.7 macrophages and primary bone marrow-derived macrophages. Results demonstrated that Rg1 treatment effectively suppressed apoptosis and the expression of phosphorylation level of mTOR induced by serum deprivation in Raw264.7 macrophages; the expressions of autophagic flux-related proteins including Atg5, Beclin1, microtubule-associated protein 1 light chain 3 (LC3), p62/SQSMT1, and the phosphorylation level of AMPK were concomitantly up-regulated. 3-Methyl-adennine (3-MA), the most widely used autophagy inhibitor, strongly up-regulated the expression of cleaved caspase-3, and blocked the anti-apoptosis function of Rg1 in macrophages. Importantly, autophagic flux was activated by Rg1, while Beclin1 knockdown partially abolished the anti-apoptosis of Rg1. Moreover, compound C, an AMPK inhibitor, partially decreased the expressions of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1, which were increased by Rg1. AICAR, an AMPK inducer, promoted the protein expressions of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1. In conclusion, Rg1 significantly suppressed apoptosis induced by serum deprivation in macrophages. Furthermore, Rg1 could effectively induce the autophagic flux by attenuating serum deprivation-induced apoptosis in Raw264.7 macrophages through activating the AMPK/mTOR signaling pathway.

Chaperonin containing TCP1 subunit 5 is a tumor associated antigen of non-small cell lung cancer.

Novel tumor antigens and their related autoantibodies have tremendous potential for early diagnosis of non-small cell lung cancer (NSCLC). In this study, we identify antigens from NSCLC tissue and autoantibodies in sera of patients with NSCLC using a modified proteomics-based approach. We seperated and identified four NSCLC-associated proteins extracted from the cytosol in tumor tissues by mini-two-dimensional gel electrophoresis, followed by Western blot and hybridization with individual sera for confirmation of antibody binding. Of the proteins we identified, we selected 58 kDa chaperonin containing TCP1(T-Complex Protein 1) subunit 5 (CCT5) for validation. Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were measured in all serum samples with an immunoluminometric assay and a receiver operating characteristic (ROC) curve was analyzed for autoantibodies against CCT5, CEA and CYFRA 21-1. The results show that CCT5 can induce an autoantibody response in NSCLC sera and show higher expression in NSCLC tissues by immunohistochemistry and Western blot. Anti-CCT5 autoantibody was found in 51% (23/45) of patients with NSCLC, but only 2.5% (1/40) in non-tumor individual controls. A receiver operating characteristic curve constructed with a panel of autoantibodies against CCT5 (AUC=0.749), CEA (AUC=0.6758), and CYFRA 21-1(AUC=0.760) show a sensitivity of 51.1% and 97.5% specificity in discriminating NSCLC from matched controls. These results indicate the potential utility of screening autoantibodies in sera, show that CCT5 could be used as a biomarker in cancer diagnosis.

Expression of p27 and PTEN and clinical characteristics in early laryngeal squamous cell carcinoma and their correlation with recurrence.

Laryngeal squamous cell carcinoma is a common malignant tumor of otolaryngeal region. At present, effective treatment of laryngeal squamous cell carcinoma still depends on surgery and radiotherapy. In recent years, application of CO2 laser resection in the treatment of stage T1 glottic carcinoma can remove the tumor completely and reduce the injury of laryngeal tissues. But recurrence still happened in some postoperative patients. Here, we selected 131 patients to compare the therapeutic effects of CO2 laser resection and traditional split laryngeal surgery on the early laryngeal cancer, examined the expression of p27 and PTEN by immunohistochemistry in early laryngeal squamous cell carcinoma tissues in correlation to clinical outcome. After two years follow-up 14/85 (16.5%) of CO2 laser treatment group presented with local recurrence (recurrent group), while that of split laryngeal surgery group was 6/46 (13.0%). There was no statistical significance in recurrence rate between the two groups (P>0.05). 10 of all the 111 (9.0%) non-recurrent patients did not follow the doctor's advice to quit smoking after the operation, while 12 in the 20 (60.0%) recurrent patients did not; the difference between the two groups was statistically significant (P<0.01). The positive rates of p27 were 80.2% (105/131) and 43.5% (57/131), and that of PTEN were 83.2% (109/131) and 48.9% (64/131) in the cancer adjacent tissues (negative surgical margin tissues) and in laryngeal carcinoma tissues, respectively (P<0.001). The expression rates of p27 and PTEN in laryngeal carcinoma tissues of the recurrent group were 20.0% (4/20), 10.0% (2/20) and that in non recurrent group were 47.7% (53/111) and 55.9% (62/111), respectively, with a significant difference (P<0.001). In addition, the expression of p27 and PTEN in tumor resected marginal tissues of the recurrence group was 50.0% (10/20), 40.0% (8/20) and that in non recurrence group was 85.6% (95/111) and 91.0% (101/111), respectively; the difference was also statistically significant between both groups (P<0.001). In conclusion, there is no statistically significant difference in tumor recurrence rate between CO2 laser surgery and traditional split laryngeal surgery. Postoperative recurrence is closely related to resume smoking. The recurrence rate of p27 and/or PTEN-negative patients was higher than that of the positive ones,that should be followed up closely after treatment.

Over-expression of p53, p21 and Cdc2 in histologically negative surgical margins is correlated with local recurrence of laryngeal squamous cell carcinoma.

The aim of this study was to explore the relationship between the expression of p53, p21 and Cdc2 in the early laryngeal cancer with negative pathological margins and its local recurrence. During 2004-2010, a total of 85 patients with early laryngeal cancer were selected in Tangshan Union Hospital, Hebei, China, and immunohistochemical method was used to detect the expression of p53, p21 and Cdc2 in the negative pathological margin tissues. All patients were followed up for two years to collect pathological data for evaluating the survival and tumor recurrence. Two years after surgery 14 of 85 patients with laryngeal cancer presented with recurrence (recurrent group), while 71 patients without recurrence (none recurrent group). The positive rate of p53, p21 and Cdc2 protein in laryngeal cancer tissues was 60.0% (51/85), 38.8% (33/85) and 70.6% (60/85), respectively, while that of the three proteins in the cancer adjacent tissues was 36.5% (31/85), 21.2% (18/85) and 29.4% (25/85), respectively. The differentiation and TNM stage of tumor had no correlation with the three proteins. The positive rate of p53 in the surgical margin of the recurrent group and non recurrent group was 71.4% (10/14) and 29.6% (21/71) (P = 0.003), that of p21 was 50.0% (7/14) and 15.5% (11/71), (P = 0.011) and Cdc2 was 57.1% (8/14) and 23.9% (17/71) (P = 0.030), respectively. In conclusion, p53, p21 and Cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma. Overexpression of p53, p21 and Cdc2 in the surgical margin of early laryngeal cancer is closely related to local recurrence of tumor.

Down-regulation of microRNA-181b is a potential prognostic marker of non-small cell lung cancer.

The aim of this study was to investigate the clinical significance of microRNA-181b (miR-181b) expression in non-small cell lung cancer (NSCLC). MiR-181b expression in 126 pairs of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by real-time quantitative RT-PCR assay. Additionally, the correlation of miR-181b expression with clinicopathological factors or prognosis of patients was analyzed. At first, miR-181b expression was significantly down-regulated in NSCLC tissues as compared with their normal counterparts (P<0.001). Then, the low miR-181b expression was found to be closely correlated with larger tumor size (P=0.02), higher p-TNM stage (P=0.008) and positive lymph node metastasis (P=0.03) of NSCLC patients. After that, survival analysis found that the overall survival (P=0.001) and disease-free survival (P=0.008) of NSCLC patients with low miR-181b expression were both significantly poorer compared to those patients with high miR-181b expression. Finally, both univariate and multivariate analyses demonstrated that low miR-181b expression may be a poor prognostic marker of NSCLC patients. This is the first study to indicate that down-regulation of miR-181b may be correlated with aggressive disease progression and poor prognosis of NSCLC patients, suggesting that miR-181b might be involved in lung carcinogenesis and become a potential prognostic marker for NSCLC.

[Relationship between expression of caveolin-1 and pERK1/2 and prognosis in non-small cell lung cancer].

OBJECTIVE: To study the relationship between expression of caveolin-1 (Cav-1) and pERK1/2 and prognosis in non-small cell lung cancer (NSCLC). METHODS: Cav-1 and pERK1/2 protein expression was assessed by immunohistochemistry in samples obtained from 160 patients with NSCLC and 20 patients with normal lung tissue. RESULTS: Normal bronchial and alveolar epithelial cells were positive for Cav-1 (membranous and cytoplasmic staining patterns). The expression rate of Cav-1 in NSCLC was 65.6% (105/160), which was significantly lower than that in normal lung tissue (P = 0.002). The Cav-1-positive rates in well to moderately differentiated tumors and poorly differentiated tumors were 56.8% (46/81) and 75.7% (53/70), respectively (P = 0.015). The expression of Cav-1 was much higher in patients with lymph node metastasis (77.8%, compared with 55.7% in lymph node-negative group, P = 0.003). The expression was also higher in stage III to IV than in stage I to II disease (75.4%, compared with 58.2%, P = 0.024). The overall survival of patients with Cav-1-positive tumors (71.4%, 37.1% and 17.1% 1-, 3- and 5-year survival, respectively) was lower than those with Cav-1-negative tumors (89.1%, 69.1% and 43.6% 1-, 3- and 5-year survival, respectively, P = 0.000). On the other hand, normal bronchial and alveolar epithelial cells were negative for pERK1/2. The expression rate of pERK1/2 in NSCLC was 61.3%, which was significantly higher than that in normal lung tissues (P = 0.000). The pERK1/2-positive rates in well to moderately differentiated tumors and poorly differentiated tumors was 53.1% and 71.4%, respectively (P = 0.021). The expression of pERK1/2 was much higher in patients with lymph node metastasis (80.6%, compared with 45.5% in lymph node-negative group, P = 0.000). The expression of pERK1/2 was also higher in stage III to IV than in stage I to II disease (76.8%, compared with 49.5%, P = 0.426). The overall survival of patients with pERK1/2-positive tumors (74.5%, 42.9% and 19.4% 1-, 3- and 5-year survival, respectively) was lower than those with pERK1/2-negative tumors (82.3%, 56.5% and 37.1% 1-, 3- and 5-year survival, respectively, P = 0.002). Cav-1 and pERK1/2 expression showed negative correlation (P = 0.000). CONCLUSIONS: Cav-1 expression is lower in NSCLC than in normal lung tissue, whereas pERK1/2 expression is higher in NSCLC. Positive expression of Cav-1 and overexpression of pERK1/2 correlates with tumorigenesis and tumor progression of NSCLC. Cav-1 and pERK1/2 may serve as potential markers for predicting prognosis in NSCLC.