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.
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.
Objective To compare the perioperative results between uniportal and three-portal thoracoscopic lobectomy for non-small cell lung cancer (NSCLC). Methods Electronic databases including PubMed, Web of Science, EMbase, CNKI, Wanfang were systematically searched from the establishment of each database until April 2022. Literature screening, data extraction and bias risk assessment were independently conducted by two researchers. All combined results were performed by RevMan 5.3 and Stata 16.0. The quality of the literature and the risk of bias were evaluated using the Cochrane Bias Risk Assessment Tool. Results Eighteen eligible randomized controlled trials (1 597 patients) were identified eventually, including 800 patients undergoing uniportal thoracoscopic lobectomy and 797 patients undergoing three-portal thoracoscopic lobectomy. Meta-analysis results showed that compared to the three-portal approach, uniportal lobectomy took longer operation time (WMD=7.63, 95%CI 2.36 to 12.91, P=0.005) with less intraoperative blood loss (WMD=–28.81, 95%CI –42.54 to –15.08, P<0.001). Furthermore, patients undergoing uniportal lobectomy achieved lower visual analogue score within 24 hours after the operation (WMD=–1.60, 95%CI –2.26 to –0.94, P<0.001), less volume of drainage after the operation (WMD=–25.30, 95%CI –46.22 to –4.37, P=0.020), as well as shorter drainage duration (WMD=–0.36, 95%CI –0.72 to –0.01, P=0.040). Besides, patients undergoing uniportal lobectomy were also observed with shorter length of hospital stay (WMD=–2.28, 95%CI –2.68 to –1.88, P<0.001) and lower incidence of postoperative complications (RR=0.49, 95%CI 0.38 to 0.63, P<0.001). However, the number of lymph nodes harvested during the operation (WMD=–0.01, 95%CI –0.24 to 0.21, P=0.930) was similar between the two groups. Conclusion Both uniportal and three-portal thoracoscopic lobectomy for NSCLC are safe and feasible. The uniportal approach is superior in reducing short-term postoperative pain, postoperative complications and shortening the length of hospital stay.
ObjectiveTo compare the 5-year survival rates between two different follow-up patterns of postoperative stage Ⅰ-ⅢA non-small cell lung cancer (NSCLC) patients.MethodsPathological stage Ⅰ-ⅢA NSCLC 11 958 patients who underwent surgical resection and received follow-up within 6 months after initial diagnosis through telephone follow-up system were included in nine hospitals from July 2014 to July 2020. The patients were divided into two groups including a proactive follow-up group (n=3 825) and a passive follow-up group (n=8133) according to the way of following-up. There were 6 939 males and 5 019 females aged 59.8±9.5 years. The Kaplan-Meier and Cox proportional hazards regression model were used.ResultsThe median follow-up frequency was 8.0 times in the proactive follow-up group and 7.0 times in the passive follow-up group. The median call duration was 3.77 minutes in the proactive follow-up group and 3.58 minutes in the passive follow-up group. The 5-year survival rate was 81.8% and 74.2% (HR=0.60, 95CI 0.53-0.67, P<0.001) in the proactive follow-up group and the passive follow-up group, respectively. Multivariate analysis showed that follow-up pattern, age, gender and operation mode were independent prognostic factors, and the results were consistent in all subgroups stratified by clinical stages.ConclusionThe proactive follow-up leads to better overall survival for resected stage Ⅰ-ⅢA NSCLC patients, especially in the stage ⅢA.
ObjectiveTo detect mRNA and protein expression of CUG-binding protein 1(CUGBP1)in non-small cell lung cancer (NSCLC), and assess the prognostic significance of CUGBP1.
MethodsFifty-seven NSCLC patients who received surgical resection at the Department of Thoracic Surgery of Affiliated Hospital of Qingdao University between July 2009 and April 2011 were enrolled in this study. There were 32 male and 25 female patients with their age of 43-74 (60.6±8.9) years. The expressions of CUGBP1 mRNA and protein in tumor and adjacent normal tissues were detected by semi-quantitative RT-PCR and immunohistochemistry. All the patients were followed up every 2 months after discharge via the phone. Time to progression(TTP) was used to evaluate the relationship between CUGBP1 mRNA, clinicopathological variables and prognosis. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ2 test. The prognostic significance of CUGBP1 mRNA was assessed by univariate and multivariate analysis using Cox regression analysis.
ResultsThe expressions of CUGBP1 mRNA and CUGBP1 were over-expressed in cancer tissue, and were significantly correlated with TNM-stage and differentiation. Univariate and multivariate analysis showed that CUGBP1 mRNA expression(P=0.0074, HR=3.701, 95% CI 1.420-9.648), TNM-stage (P < 0.000 1, HR=4.043, 95% CI 2.098-7.794) and age (P=0.0018, HR=3.207, 95% CI 1.544-6.664) were independent predictors of postsurgical survival in NSCLC patients.
ConclusionsCUGBP1 mRNA and CUGBP1 are over-expressed in NSCLC, and over-expression of CUGBP1 mRNA independently predicts a shorter postsurgical survival in NSCLC patients.
