Objective To explore whether blood exosome carrying miR-140-3p can regulate the malignant progression of small cell lung cancer (SCLC) through targeting ubiquitin-conjugating enzyme E2C (UBE2C). MethodsThis study was consisted of bioinformatics analysis, clinical research, cell analysis, and animal experiments. We searched GEO database for data of SCLC related microRNA (miRNA) dataset GSE19945, mRNA dataset GSE40275, and GSE60052. T-test was used to detect the differential expression of miR-140-3p in normal tissues and SCLC tissues in the dataset, and the expression of miR-140-3p in different tissues and extracellular vesicles was analyzed through a database. SCLC tissue and paired cancerous tissues excised at Yongzhou Central Hospital were collected between December 2021 and December 2022, and healthy volunteers 7 days before the start of the study was selected. Quantitative real-time polymerase chain reaction was used to detect the expression level distribution of miR-140-3p and UBE2C in tissue samples of SCLC patients and healthy volunteers. SCLC patients were divided into low expression and high expression groups based on the median expression level, and the correlation between the expression levels of miR-140-3p and UBE2C and patient pathological parameters was analyzed. 20 male nude mice was selected. The nude mice were randomly divided into 4 groups: miR-140-3p, UBE2C analog negative control group, and analog control group, with 5 mice in each group. Immunohistochemical detection system was used to detect tumor tissue sections in nude mice. Results A total of 45 patients and 30 healthy volunteers were included. SCLC malignant progression was significantly associated with the expression of miR-140-3p and UBE2C. The expression of miR-140-3p was low in blood-derived exosomes from SCLC patients. Overexpression of miR-140-3p inhibited the proliferation (47.33±2.52 vs. 107.67±10.69, P<0.05), migration [(11.63±2.62)% vs. (31.77±4.30)%, P<0.05] and invasion (44.33±3.06 vs. 102.67±8.50, P <0.05) and promoted their apoptosis [(14.48±1.20)% vs. (10.14±1.21)%, P<0.05]. Bioinformatics analysis yielded the target gene UBE2C of miR-140-3p. In vitro experiments further demonstrated that miR-140-3p directly targetd UBE2C to inhibit SCLC cell proliferation, migration, invasion, epithelial mesenchymal transition, and promote apoptosis. Mouse xenotransplantation experiments showed that miR-140-3p mimic significantly inhibited tumor growth. ConclusionTherefore, the miR-140-3p extracellular vesicle and the oncogenic gene UBE2C may be potential targets for inhibiting the malignant progression of SCLC.
Objective To evaluate the survival outcomes of segmentectomy versus lobectomy for T1c non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI (China National Knowledge Infrastructure), and Wanfang Data, with the search time limit set from the inception of the databases to February 2024. Three researchers independently screened the literature, extracted relevant information, and evaluated the risk of bias of the included literature according to the Newcastle-Ottawa Scale (NOS). Meta-analysis was conducted using STATA 15.1. Results A total of 8 retrospective cohort studies were included, involving 7 433 patients. The NOS scores of the included studies were all ≥7 points. Patients who underwent lobectomy had significantly higher five-year overall survival (OS) rates compared to those who underwent segmentectomy (adjusted HR=1.11, 95%CI 0.99-1.24, P=0.042). Compared with lobectomy, segmentectomy showed no significant difference in adjusted three-year OS rate (adjusted HR=0.88, 95%CI 0.62-1.24) and adjusted five-year lung cancer-specific survival (adjusted HR=1.10, 95%CI 0.80-1.51, P=0.556) of patients with T1c NSCLC. Moreover, there were no differences in the five-year adjusted relapse-free survival (adjusted HR=1.23, 95%CI 0.82-1.85, P=0.319), and adverse events (OR=0.57, 95%CI 0.37-0.90, P=0.015) in the segmentectomy group were significantly less than those in the lobectomy group. Subgroup analysis based on whether patients received neoadjuvant therapy showed that among studies that excluded patients who received neoadjuvant therapy, no significant difference in 5-year adjusted OS rate was observed between the segmentectomy group and lobectomy group (adjusted HR=1.02, 95%CI 0.81-1.28, P=0.870). Conclusion Segmentectomy and lobectomy show no significant difference in long-term survival in stage T1c NSCLC patients, with segmentectomy associated with fewer postoperative complications. Further high-quality research is needed to con?rm the comparative ef?cacy and safety of lobectomy and segmentectomy for T1c NSCLC patients.
Objective To systematically evaluate the benefits and safety of anti-PD-1/PD-L1 antibody in the treatment of advanced non-small cell lung cancer (NSCLC). Methods Randomized controlled trials (RCTs) about anti-PD-1/PD-L1 antibody versus conventional-dose chemotherapy in the treatment of advanced NSCLC were searched in PubMed, EMbase, The Cochrane Library (Issue 8, 2016), Web of Science, CBM, CNKI, and VIP databases from inception to September 2016. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of eligible studies, then meta-analysis was conducted by using RevMan 5.3 software. Results A total of five RCTs involving 2 580 patients were included. The results of meta-analysis showed that: the objective response rate (ORR) and one year overall survival rate (OSR1y) in anti PD-1/PD-L1 monoclonal antibody group were higher than that of the conventional chemotherapy group (RR=1.86, 95%CI 1.37 to 2.52,P<0.001; RR=1.37, 95%CI 1.23 to 1.52,P<0.001, respectively). However, there were no significant differences between two groups in one-year progression-free survival rate (PFSR1y) (RR=1.85, 95%CI 0.61 to 5.59,P=0.28) and disease control rate (DCR) (RR=1.13, 95%CI 0.76 to 1.68,P=0.55). With regard to untoward effect, rate of adverse effects (AEs) and AEs of 3-5 grade in anti PD-1/PD-L1 monoclonal antibody group were higher than those of the conventional chemotherapy group (RR=0.85, 95%CI 0.76 to 0.95,P=0.004; RR=0.28, 95%CI 0.18 to 0.43,P<0.001), the difference was statistically significant. But there was no significant difference in AEs to discontinuation between the two groups (RR=0.60, 95%CI 0.26 to 1.39,P=0.23). Conclusion Compared with conventional-dose chemotherapy, anti-PD-1/PD-L1 antibody has considerable current effect and safety in the treatment of advanced NSCLC.
ObjectiveTo explore the relationship between Beclin 1 level and lymph node metastasis in patients with non-small cell lung cancer.MethodA total of 204 surgical specimens of patients with non-small cell lung cancer from September 2011 to September 2016 were collected in our hospital. There were 116 males and 88 females . Beclin 1 levels were detected by Western blotting. There were 116 males and 88 females at average age of 55.3±11.2 years. The patients were divided into three groups including a group N0 (no lymph node metastasis), a group N1(intralobar and interlobar lymph node metastases, and no mediastinal lymph node metastasis), and a group N2 (mediastinal lymph node metastasis). The differences of Beclin 1 levels in tumor tissues and lymph nodes of patients with N0, N1 and N2 were statistically analyzed.ResultsAmong 204 patients of lung cancer, 36 patients were squamous cell carcinoma and 168 patients were adenocarcinoma. The levels of Beclin 1 in tumor tissues of N0, N1 and N2 groups decreased gradually with a statistical difference (P<0.05). In the three groups, the levels of Beclin 1 in the lung hilum and intrapulmonary lymph nodes (N1 Beclin 1) of N1 and N2 groups were less than that of N0 group with a statistical difference (P<0.01). In the three groups, the level of Beclin 1 in the mediastinal lymph nodes (N2 Beclin 1) of N2 group was less than that of the N0 and N1 groups with a statistical difference (P<0.01). In the N1 group, the level of N1 Beclin 1 was less than that of N2 group (P<0.01). In the N2 group, though the level of N1 Beclin 1 was less than N2 Beclin 1, there was no statistical difference (P>0.05). ConclusionBeclin 1 level can be used as a reference index to judge the benign and malignant lung masses, and lymph node Beclin 1 level can be used as an important reference index to help determine whether there is lymph node metastasis in lung cancer.
Objective To systematically review the efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer(NSCLC). Methods An electronically search was conducted in The Cochrane Library, PubMed and EMbase databases from inception to December 2016 to collect randomized controlled trials (RCTs) about tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy for NSCLC. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 RCTs involving 6 559 patients were finally included. The results of meta-analysis showed that: The median progression free survival (PFS) (HR=0.86, 95%CI 0.81 to 0.91, P<0.001) and objective response rate (ORR) (HR=1.43, 95%CI 1.20 to 1.70,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy were significantly longer than those of the chemotherapy group. There were no significant differences between two groups in incidence of median overrall survival (OS) (HR=0.91, 95%CI 0.82 to 1.00,P=0.06), fatigue (RR=1.03, 95%CI 0.97 to 1.11, P=0.33), dyspnea (RR=1.01, 95%CI 0.91 to 1.13, P=0.82) and cough (RR=1.01, 95%CI 0.89 to 1.15, P=0.91). However, the incidence of neutrocytopenia (RR=1.16, 95%CI 1.05 to 1.28, P=0.003), thrombocytopenia (RR=1.46, 95%CI 1.23 to 1.73, P<0.001), diarrhea and hypertension (RR=2.91, 95%CI 2.28 to 3.71,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy group were significantly higher than those of the chemotherapy group. The tyrosine kinase inhibitors combined with chemotherapy group had lower rate of anemia (RR=0.86, 95%CI 0.75 to 0.98,P=0.03). Conclusion Compared with chemotherapy alone, tyrosine kinase inhibitors combined with chemotherapy can improve the median PFS and ORR while it can be used as a treatment for advanced non-small cell lung cancer patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
Objctive To explore the effect of positive lymph nodes ratio (LNR) on prognosis of patients with non-small cell lung cancer (NSCLC). Methods Clinical data of 432 NSCLC patients undergoing radical surgery for lung cancer and systemic lymph node dissection in our hospital from January 2010-2013 were retrospectively analyzed. There were 316 males and 116 females with age of 39-84 (57.59±9.16) years. Among 432 patients, 229 (53.0%) were classified as N0 based on pathological staging of lymph nodes, 104 (24.1%) as N1 and 99 (22.9%) as N2. Kaplan-Meier curve and COX multi-factor regression model were used to evaluate the correlation between the clinical data and patients' survival. Results Five lymph nodes on average (range, 1-52) were removed in each patient. Kaplan-Meier survival curves showed that the higher the staging of positive lymph nodes was, the shorter the patients' overall survival and disease-free survival were (P<0.001). Survival analysis showed that the LNR was closely associated with disease-free survival and overall survival (P<0.001). COX multivariate analysis revealed that the LNR staging was an independent risk factor of prognosis of NSCLC. Conclusion LNR is an independent prognostic factor of NSCLC, and can be used to improve lymph node staging in standards for NSCLC staging in the future.
ObjectiveTo elucidate the clinical pattern of pulmonary lymph node metastasis and the significance of station No.12 and No. 13 lymph nodes biopsy in patients with non-small cell lung cancer (NSCLC). MethodsThirty-eight NSCLC patients underwent standard radical resection of pulmonary carcinoma and systemic lymphadenectomy between January 2015 and June 2015. There were 29 males and 9 females with a mean age of 61.1±15.4 years (ranged from 44 to 73 years). There were 20 patients of squamous carcinoma, 17 patients of adenocarcinoma and 1 patient of sarcomatoid carcinoma. All patients didn't receive radioor chemotherapy before the operation. All the lymph nodes in the surgical specimens were marked and sampled for pathology examination. ResultsWe obtained 652 lymph nodes in total (17.2 per patient). Seventy-eight lymph nodes of 24 patients showed lymphatic metastasis with a metastasis degree of 12.0% (78/652) and a metastasis rate of 63.2% (24/38). Among which there were 22 patients of N1 metastasis, 10 of N1+N2 and 2 of N2 skipping metastasis. Routine pathological examination of N1 metastasis demonstrated 12 patients of positive station No.12 and No.13 lymph nodes with the metastasis rate of 31.6%. The total amount of dissected lymph nodes was 95, among which there were 14 lymphatic metastasis with the metastasis rate of 14.7%. Four patients with nodal involvement in lymph node stations No.12 or No.13 were identified from 18 patients without mediastinal and intrapulmonary lymph node metastases confirmed by routine pathological examination. The detection rate was 22.2% (4/18) and the rate of N1 missed diagnosis was 33.3% (4/12). Univariate and multivariate analysis suggested that the metastasis degree of pulmonary lymph nodes of station No.12 and No.13 was associated with tumor differentiation grade (χ2=6.453,P=0.011), while it didn't show any significant differences as to pathology subtype (χ2=0.118, P=0.732), tumor size (χ2=0.930, P=0.759), or tumor classification (χ2=1.648, P=0.199). ConclusionPulmonary lymph node metastasis occupies an important place in the process of lung cancer metastasis. Patients with NSCLC especially those of poorly differentiated should be pathologically examined regularly in order to improve the accuracy of staging.
ObjectiveTo investigate the expression of autophagy-related genes and proteins in the lung tissues of patients with non-small cell lung cancer (NSCLC).MethodsPulmonary tissues were obtained from the surgically resected lung tissues of patients with NSCLC who were clinical diagnosed. The lung cancer tissues were derived from the pathologically diagnosed NSCLC and the normal tissues were from lung tissues 5 cm away from the lung lesions (29 cases in the lung cancer group and 32 cases in the normal group). The expression of autophagy-related proteins ATG5, LC3B, and p62 in lung tissues were measured by Western blot, and mRNA expression of ATG5 and p62 in the lung tissues were measured by real-time PCR.ResultsWestern blot analysis showed that the expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). However, the expression of LC3B in lung cancer group was significantly lower than that in normal group (P<0.05). Real-time PCR analysis found that the mRNA expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). The expression of ATG5, LC3B and p62 had no relationship with gender, age, smoking history, tumor location, tumor size, clinicopathological classification, differentiation or TNM stage. The expression of ATG5 had statistical significance in lymph node metastasis (P<0.05), but there was no difference for LC3B or p62 in lymph node metastasis (P>0.05).ConclusionsAutophagy plays a role in the tumorigenesis of lung cancer. If it’s possible to regulate and control autophagy-related genes and proteins effectively, it may supply new insights or targets into treatment for lung cancer patients.
ObjectiveTo investigate the clinical value of prophylactic high-flow nasal cannula oxygen therapy (HFNC) in reducing postoperative pulmonary complication (PPC) in elderly patients with non-small cell lung cancer (NSCLC). Methods The clinical data of elderly patients (over 60 years) with NSCLC who underwent video-assisted thoracoscopic lobectomy or segmental resection at the Department of Thoracic Surgery, Fujian Provincial Hospital from January 2021 to March 2022 were retrospectively analyzed. According to whether receiving HFNC after surgery, they were divided into a conventional oxygen therapy (CO) group and a HFNC group. The CO group were matched with the HFNC group by the propensity score matching method at a ratio of 1 : 1. We compared PPC incidence, white blood cell (WBC) count, procalcitonin and C-reactive protein on postoperative day (POD) 1, 3 and 5 and postoperative hospital stay between the two groups. ResultsA total of 343 patients (165 males, 178 females, average age of 67.25±4.79 years) were enrolled, with 53 (15.45%) receiving HFNC. Before matching, there were statistical differences in gender, rate of combined chronic obstructive pulmonary disease, pathology type and TNM stage between the two groups (all P<0.05). There were 42 patients successfully matched in each of the two groups, with no statistical difference in baseline characteristics (P>0.05). After propensity score matching, the results showed that the PPC incidence in the HFNC group was lower than that in the CO group (23.81% vs. 45.23%, P=0.039). WBC count on POD 3 and 5 and procalcitonin level on POD 3 were less or lower in the HFNC group than those in the CO group [ (8.92±2.91)×109/L vs. (10.62±2.67)×109/L; (7.68±1.58)×109/L vs. (8.86±1.76)×109/L; 0.26 (0.25, 0.44) μg/L vs. 0.31 (0.25, 0.86) μg/L; all P<0.05]. There was no statistical difference in the other inflammatory indexes or the postoperative hospital stay between the two groups (P>0.05). Conclusion Prophylactic HFNC can reduce the PPC incidence and postoperative inflammatory indexes in elderly patients with NSCLC, but does not shorten the postoperative hospital stay.
Objective To investigate the prognostic value of sarcopenia in patients with early non-small cell lung cancer (NSCLC) after surgery and chemotherapy. Methods This study included 592 patients with early non-small cell lung cancer who received lung cancer resection from January 2014 to December 2015, and they were divided into two groups: 473 patients received surgery alone (the surgery group), 119 patients received chemotherapy after surgery (the postoperative chemotherapy group), and the two groups were divided into sarcopenia group and non-sarcopenia group. General clinical data, laboratory data, and imaging data of these patients were compared. Results The median follow-up time of 592 patients was 69.1 months [95% confidential interval (CI) 64.9 - 78.2], and 110 patients were with sarcopenia (18.6%). Multivariate analysis showed that sarcopenia was an independent adverse prognostic factor in the surgery group [hazard ratio (HR) 6.56; 95%CI 1.86 to 14.78; P=0.01]. For patients undergoing postoperative chemotherapy, skeletal muscle mass index was reduced after chemotherapy, and sarcopenia was an independent predictor of poor prognosis (HR 5.77; 95%CI 0.96 to 20.60; P<0.05). Conclusions Sarcopenia is an independent poor prognostic factor for patients with early NSCLC undergoing surgery and postoperative chemotherapy. Assessment of sarcopenia before surgery and postoperative chemotherapy is helpful to improve the prognosis of patients with early NSCLC.