Objective To explore the association between the preoperative systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients. Methods A comprehensive literature survey was performed on PubMed, Web of Science, EMbase, The Cochrane Library, Wanfang, and CNKI databases to search the related studies from inception to December 2021. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the preoperative SII with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) in NSCLC patients. Results A total of 11 studies involving 9 180 patients were eventually included. The combined analysis showed that high SII levels were significantly associated with worse OS (HR=1.61, 95%CI 1.36-1.90, P<0.001), DFS (HR=1.50, 95%CI 1.34-1.68, P<0.001), and RFS (HR=1.17, 95%CI 1.04-1.33, P<0.001). Subgroup analyses also further verified the above results. Conclusion Preoperative SII is a powerful prognostic biomarker for predicting outcome in patients with operable NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed and prospective studies are warranted to verify our findings.
Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.
ObjectiveTo explore the effects of silencing the expression of ubiquitin-conjugating enzyme E2T (UBE2T) gene on proliferation, apoptosis, migration and invasion abilities of A549 cells.MethodsA549 cells were cultured in vitro. Three sets of shRNA-UBE2T plasmid vectors (UBE2T-shRNA1 group, UBE2T-shRNA2 group, UBE2T-shRNA3 group) and shRNA-NC (shRNA-NC group) were constructed, respectively. A549 cells were transfected with lipofection transfection. The cells transfected with empty vector were enrolled as control (control group). The transfection efficiency was detected by RT-PCR. The effects of silencing the expression of UBE2T gene on biological behaviors (proliferation, apoptosis, migration, and invasion) of lung cancer A549 cells were detected by clone formation assay, flow cytometry, Transwell assay and scratch test. The expression of proliferation and apoptosis related proteins, and expression of PI3K/AKT signaling pathway proteins were detected by Western blot. ResultsAfter transfection, expression level of UBE2T mRNA in UBE2T-shRNA1 group, UBE2T-shRNA2 group and UBE2T-shRNA3 group was significantly down-regulated (all P<0.05), whose down-regulation was the most significant in UBE2T-shRNA3 group (P<0.05). Compared with control group and shRNA-NC group, clone formation rate, number of invasion A549 cells, scratch healing rate, Ki67 expression, PCNA expression, p-PI3K/PI3K ratio and p-AKT/AKT ratio were significantly decreased in UBE2T-shRNA3 group (P<0.05), while A549 apoptosis rate, Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio were significantly increased (P<0.05). There were no significant differences in the above indexes between control group and shRNA-NC group (P>0.05). ConclusionsThe shRNA interfering with UBE2T is reliable to construct the model of A549 cells with stable low-expression UBE2T. Down-regulation of UBE2T expression can promote apoptosis of A549 cells, inhibit their proliferation, invasion and migration abilities. The mechanism may be related to inhibiting the activation of PI3K/AKT signaling pathway.
ObjectiveTo explore the suppression of Wnt-1 pathway on non-small cell lung cancer (NSCLC) by establishing a NSCLC nude mice model of transplanting tumor in Xuanwei county.
MethodsThere were 21 mice with tumor weight from 16-18 g and we divided them into a blank group (n=7), a control group (n=7), and an experiment group (n=7). The blank group were injected with saline, the control group were injected with docetaxel, and the experimental group were injected with Wnt-1 antibody. The mice were executed and the tumor specimens were obtained after six injections. We compared the volumes of the specimens and the inhibition rates of tumor among the three groups.
ResultsThere was a statistical difference in volume between the blank group and the experiment group as well as the control group on the 21th and 27th day (P=0.002,P=0.000). The experiment within mice's body showed that both docetaxel and Wnt-1 antibody could inhibit NSCLC from growing, and the inhibition effect of docetaxel was stronger.
ConclusionThe interdiction of Wnt-1 pathway is functional to restrain the growth of tumor. The docetaxel and Wnt-1 antibody have a positive effect on the treatment of 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.
As emerging means of cancer treatment, immunotherapy is the fourth major therapeutic strategy after surgery, chemoradiotherapy, and targeted therapy, which benefits patients a lot. It has been more than 100 years for the medical community exploring how to harness the immune system to fight cancer. Since the advent of ipilimumab in 2011, the first checkpoint inhibitor, cancer immunotherapy represented by checkpoint inhibitors has exploded. Several programmed death protein-1 and programmed cell death ligand-1 inhibitors have successively been approved to treat advanced non-small cell lung cancer in the second-line setting or even the first-line setting. But checkpoint inhibitors therapy has only achieved limited benefit at the present stage. Exploring potential predictive biomarkers and mechanisms of resistance are in need of further consideration to optimize immunotherapy.
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 systematically evaluate the efficacy of neoadjuvant chemoradiotherapy or chemotherapy followed by surgery versus definitive chemoradiation in stage ⅢA-N2 non-small cell lung cancer (NSCLC).MethodsWe searched PubMed, EMbase, Web of Science and The Cochrane Library to collect clinical studies on the efficacy comparison between neoadjuvant chemoradiotherapy or chemotherapy followed by surgery and definitive chemoradiation in stage ⅢA-N2 NSCLC from inception to September 2022. The meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 9 studies (3 randomized controlled trials and 6 retrospective cohort studies) with 12 801 patients were included. The results of meta-analysis showed that there was no statistical difference in the progression-free survival rate between the inductive treatment followed by surgery (including lobectomy and pneumonectomy) and definitive chemoradiation (HR=0.99, 95%CI 0.86-1.15, P=0.91). Compared with definitive chemoradiation, the overall survival (OS) rate in the inductive treatment followed by surgery (including lobectomy and pneumonectomy) was lower (HR=1.24, 95%CI 1.09-1.42, P=0.001), while the OS rate in the inductive treatment followed by lobectomy was higher (HR=0.55, 95%CI 0.51-0.61, P<0.000 01). And the local recurrence rate in the inductive treatment followed by surgery was reduced (OR=0.44, 95%CI 0.36-0.55, P<0.000 01).ConclusionNeoadjuvant chemoradiotherapy or chemotherapy followed by lobectomy is superior to definitive chemoradiation in OS and it has a lower local recurrence rate, so lobectomy should be one of the multidisciplinary treatments for selected ⅢA-N2 NSCLC patients.
ObjectiveTo explore the potential role of tumor spread through air spaces (STAS) as a prognostic indicator of non-small cell lung cancer (NSCLC) through meta-analysis.MethodsPubMed, EMbase and Web of Science, from inception to February 2022 were searched by computer about the research of the 5-year overall survival (OS) and recurrence free survival (RFS) of NSCLC patients with or without STAS. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of each study.ResultsTotally 13 published articles were included with 4 647 patients, and1 424 (30.6%) patients had STAS. The NOS score of all studies≥6 points. The meta-analysis showed that compared with the NSCLC patients without STAS, those with STAS had a worse prognosis of 5-year RFS, and the combined HR was 1.89 (95%CI 1.61-2.23); they had a shorter 5-year OS, and the combined HR was 2.25 (95%CI 1.79-2.84). There was no statistical heterogeneity among studies.ConclusionThe presence of STAS may be a poor prognostic factor for patients with NSCLC, and enough attention should be paid. The STAS should be recorded in the pathological report to guide the comprehensive treatment and evaluate the prognosis of patients.
Objective To evaluate the value of 18 F-fluorodeoxyglucose ( 18 F-FDG) metabolism imaging in evaluating the response of patients with non-small cell lung cancer ( NSCLC) in stable diseaseafter chemotherapy. Methods 28 patients with NSCLC in stable disease after chemotherapy admitted between September 2010 to September 2012 were retrospectively investigated. The reduction ratio of targetto-nontarget ratio ( T/N) before and after chemotherapy was calculated. The patients were followed up 3 to 12 months to measure progression-free survival ( PFS) . The correlation between the reduction ratio of T/N and PFS was analyzed. The patients were divided into a reduction group and a non-reduction group according to the difference of the reduction ratio of T/N and was compared the difference of the PFS.Results The reduction ratio of T/N had positive correlation with PFS( Pearson r = 0. 668, P lt; 0. 01) . The PFS of the reduction group was longer than that in the non-reduction group ( 8. 0 ±2. 5 months vs. 5. 3 ±1. 2 months,P lt;0. 05) . Conclusions The reduction ratio of T/N is positively correlated with PFS in NSCLC patients in stable disease after chemotherapy. It is possible to evaluate the efficacy of the treatment according to the reduction ratio of T/N.
