Objective To observe the value of serum soluble receptor of advanced glycation endproducts (sRAGE) combined with lung function and high resolution lung CT (HRCT) in predicting the risk of chronic obstructive pulmonary disease (COPD) developing non-small cell lung cancer (NSCLC). Methods From January 2019 to June 2021, 140 patients with COPD combined with NSCLC, 137 patients with COPD, and 133 patients with NSCLC were enrolled in the study from the People's Hospital of Ningxia Hui Autonomous Region. General data, clinical symptoms, pulmonary function indexes and HRCT emphysema indexes (EI) were collected. Serum sRAGE levels of these patients were measured by enzyme linked immunosorbent assay. Clinical characteristics of patients with COPD complicated with NSCLC were analyzed. Serum sRAGE, lung function and lung HRCT were combined to evaluate the correlation between the degree of emphysema and the occurrence of NSCLC in COPD, and receiver operator characteristic (ROC) curve analysis was performed for diagnostic efficiency. Results Compared with NSCLC group, COPD combined with NSCLC group had higher proportion of male patients, higher proportion of elderly patients, higher smoking index, and higher proportion of squamous cell carcinoma (P<0.05). FEV1 and FEV1%pred in COPD combined with NSCLC group were significantly lower than those in COPD group and NSCLC group. The Goddard score and EI values of emphysema were significantly increased (P<0.05). Serum sRAGE was significantly lower than that of COPD group and NSCLC group (P<0.05). Serum sRAGE level was positively correlated with FEV1%pred (r=0.366, P<0.001) and FEV1/FVC (r=0.419, P<0.001), and negatively correlated with Goddard score (r=–0.710, P=0.001) and EI value (r=–0.515, P<0.001). Binary multi-factor logistic regression analysis showed that age, smoking index, EI, Goddard score, RV/TLC were positively correlated with the risk of COPD developing NSCLC, while FEV1%pred, FVC, FEV1/FVC and serum sRAGE were negatively correlated with the risk of COPD developing NSCLC. ROC curve results showed that the area under the curve (AUC) of single diagnosis of sRAGE was 0.990, and the optimal cut-off value of 391.98 pg/mL with sensitivity of 93.3% and specificity of 89.7%. The AUC of sRAGE combined with age, smoking index, EI, Goddard score, FEV1%pred, FVC, FEV1/FVC, RV/TLC was 1.000 with sensitivity of 96.7%, specificity of 96.6%, and Yoden index of 0.933. Conclusion The combination of serum sRAGE, lung function and HRCT emphysema score can improve prediction of NSCLC occurrence in COPD.
Objective To investigate the expression and clinical significance of S100A4 protein in tumorstroma of nonsmall cell lung cancer（NSCLC） to study its correlation with invasion, metastasis and prognosis. Methods Immunohistochemical staining（SP method）for S100A4 protein expression was performed in tissue sections from 130 patients with NSCLC operated and to analyze association of S100A4 protein with clinicopathological parameters in lung cancer and prognosis. Results The total positive expression rates of S100A4 protein in stroma of NSCLC was 72.3%. The positive expression rates of S100A4 protein in stroma of squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma and large cell lung cancer were 84.3%，59.6%，70.0% and 75% respectively.The expression of S100A4 protein was significantly associated with lymph node metastasis (χ2=18.91, P=0.000), distant metastasis(χ2=5.51, P=0.019) and TNM stage (χ2=21.54, P=0.000). The 3 years survival rates of patients whose tumourstroma stained positive for S100A4 was lower than that of patients whose tumourstroma stained negative (36.2% vs. 63.9%, P=0.003). Cox’ risk ratio model analysis indicated that age ≤50 years (OR=1.866), lymph node metastasis(OR=1.826), distant metastasis(OR=6.224), lower histology differentiation and undifferentiation (OR=1.793), TNM stage Ⅲ-Ⅳ (OR=2.573) and positive expression of S100A4 protein in stroma of NSCLC(OR=1.776) were significantly independent prognostic factors which affected survival. Conclusion Expression of S100A4 protein in stroma of NSCLC is significantly associated with invasion, metastasis, TNM stage and prognosis. S100A4 protein might become a marker for prediction of tumor progression of disease and clinical therapy.
Objective To study the clinicopathologic features which influence the prognosis of patients with stage Ib nonsmall cell lung cancer (NSCLC) after operation, and discuss the indication of postoperative chemotherapy. Methods From January 2002 to December 2002, the clinical materials of 152 patients who underwent complete pulmonary lobectomy and were confirmed to have stage Ib NSCLC by postoperative histopathological examination were collected from Shanghai Chest Hospital. There were 82 male and 70 female cases aged from 33-80 years. The mean age was 63.0 years. KaplanMeier method was used to compare and analyze the age, gender, tumor diameter, tumor location, lymphatic or vascular carcinoma embolus, differentiation, pleural invasion and chemotherapy of patients. Cox regression model was used to do prognostic multivariate analysis to above factors. Results The 5year survival rate was 71.1%. The median survival time was 44.20 months. The results of single factor analysis showed that the tumor diameter was longer than 5 cm（χ2=4.020，P=0.042）, lymphatic or vascular carcinoma embolus existed（χ2=14670，P=0.001）, poorly differentiated tumor（χ2=8.395，P=0.004）, and those whose tumors were located on middlelower lobars had a poor prognosis（χ2=3.980，P=0.045）. The age(χ2=0.478，P=0.740), gender(χ2=0.571，P=0.450), pathological type(χ2=0.406，P=0.816), pleural invasion(χ2=0.022，P=0.882) and postoperative chemotherapy of patients (χ2=1.067，P=0.302)had no relationship with postoperative survival. The results of multivariate analysis showed that lymphatic or vascular carcinoma embolus（P=0.006，95%CI:1.491,10.524） and poorly differentiated tumor（P= 0.001,95%CI:0.116,0.578） were the main factors which influenced the survival rate of patients. Conclusion The tumor differentiation and lymphatic or vessel carcinoma embolus of patients with stage Ib NSCLC are important factors which influence prognosis and survival rate. The poorly differentiated tumor and lymphatic or vessel carcinoma embolus could be regarded as one of the indications of postoperative chemotherapy.
Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
ObjectiveTo explore the adjuvant treatment options for elderly patients or those with low cardiopulmonary function who cannot tolerate lobectomy for peripheral solid pathological stage ⅠA (pⅠA) non-small cell lung cancer (NSCLC). MethodsA retrospective analysis was conducted on the clinical data of patients with peripheral solid pⅠA stage NSCLC treated with lobectomy and compromised sublobar resection (CSR) in our center from 2018 to 2019. The incidence of postoperative complications and independent predictors of postoperative recurrence were analyzed. Patients in the CSR group were divided into a targeted therapy group, a chemotherapy group, and an observation group based on postoperative treatment measures. The 3-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of the three subgroups before and after propensity score matching (PSM) were compared. ResultsA total of 586 patients were included, including 288 males (49.15%) and 298 females (50.85%), with a median age of 64.00 years. There were 335 patients of lobectomy and 251 patients of compromised sublobar resection. There was no statistically significant difference in the incidence of postoperative complications between the lobectomy group and CSR group [RR=0.987, 95%CI (0.898, 1.085), P=0.789). Multivariate analysis showed that gender, tumor location, and size were independent risk factors for recurrence after CSR. After PSM, 17 patients were enrolled in each of the three subgroups of CSR. Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 3-year RFS rate (P=0.115) and 5-year OS rate (P=0.101) between the targeted therapy group and the chemotherapy group after PSM, but both were significantly better than those in the observation group (P=0.041, P=0.009). Compared with lobectomy, there was no statistically significant difference in the 3-year RFS rate (P=0.069) and 5-year OS rate (P=0.540) in the targeted therapy group, while the chemotherapy group and observation group were significantly inferior to the lobectomy group (P<0.05). ConclusionCSR for treating elderly patients or those with low cardiopulmonary function with peripheral solid pⅠA stage NSCLC does not increase the incidence of postoperative complications. Gender, tumor location, and size are independent risk factors for postoperative recurrence. In terms of 3-year RFS rate and 5-year OS rate, adjuvant targeted therapy after CSR is not only superior to chemotherapy or observation but is also not inferior to lobectomy.
In recent years, the computer science represented by artificial intelligence and high-throughput sequencing technology represented by omics play a significant role in the medical field. This paper reviews the research progress of the application of artificial intelligence combined with omics data analysis in the diagnosis and treatment of non-small cell lung cancer (NSCLC), aiming to provide ideas for the development of a more effective artificial intelligence algorithm, and improve the diagnosis rate and prognosis of patients with early NSCLC through a non-invasive way.
ObjectiveTo analyze the correlation between the molecular biological information of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) and its clinical prognosis, and to explore the spatial features and molecular mechanisms of interactions between cells in the tumor microenvironment (TME) of SMARCA4-dNSCLC. MethodsUsing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), this study conducted functional enrichment analysis on differentially expressed genes (DEGs) in SMARCA4-dNSCLC and depicted its genomic variation landscape. Through weighted gene co-expression network analysis (WGCNA) and a combination of 10 different machine learning algorithms, patients in the training group were divided into a low-risk group and a high-risk group based on a median risk score (RiskScore). A corresponding prognostic prediction model was established, and on this basis, a nomogram was constructed to predict the 1, 3, and 5-year survival rates of patients. K-M survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model. External datasets from GEO further validated the prognostic value of the prediction model. In addition, we also evaluated the immunological characteristics of the TME of the prognostic model. Finally, using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome (ST), we explored the spatial features of interactions between cells in the TME of SMARCA4-dNSCLC, intercellular communication, and molecular mechanisms. ResultsA total of 56 patients were included in the training group, including 38 males and 18 females, with a median age of 62 (56-70) years. There were 28 patients in both the low-risk and high-risk groups. A total of 474 patients were included in the training group, including 265 males and 209 females, with a median age of 65 (58-70) years. A risk score model composed of 8 prognostic feature genes (ELANE, FSIP2, GFI1B, GPR37, KRT81, RHOV, RP1, SPIC) was established. Compared with patients in the low-risk group, those in the high-risk group showed a more unfavorable prognostic outcome. Immunological feature analysis revealed differences in the infiltration of various immune cells between the low-risk and high-risk groups. ScRNA-seq and ST analyses found that interactions between cells were mainly through macrophage migration inhibitory factor (MIF) signaling pathways (MIF-CD74+CXCR4 and MIF-CD74+CD44) via ligand-receptor pairs, while also describing the niche interactions of the MIF signaling pathway in tissue regions. ConclusionThe 8-gene prognostic model constructed in this study has certain predictive accuracy in predicting the survival of SMARCA4-dNSCLC. Combining the ScRNA-seq and ST analyses, cell-to-cell crosstalk and spatial niche interaction may occur between cells in the TME via the MIF signaling pathway (MIF-CD74+CXCR4 and MIF-CD74+CD44).
ObjectiveTo investigate the clinical effect of thoracoscopic lobectomy versus segmentectomy in the treatment of T1bN0M0 non-small cell lung cancer (NSCLC). MethodsClinical data of 181 patients with T1bN0M0 NSCLC admitted to our hospital from 2012 to 2015 were retrospectively analyzed. They were divided into a lobectomy group and a segmentectomy group according to surgical methods. There were 117 patients in the lobectomy group (46 males and 71 females aged 61.32±8.94 years) and 64 patients in the segmentectomy group (20 males and 44 females aged 58.55±12.57 years). Perioperative indicators and prognosis were compared between the two groups. ResultsThe segmentectomy group had longer operation time, less intraoperative blood loss, shorter postoperative hospital stay and more preservation of lung function compared with the lobectomy group (P<0.05). The lobectomy group had higher consolidation tumor ratio, bigger tumor diameter, and more lymph node sampling compared with the segmentectomy group (P<0.05). There was no statistical difference in 5-year overall survival or recurrence-free survival between the two groups (P<0.05). ConclusionFor patients with T1bN0M0 NSCLC, thoracoscopic segmentectomy and lobectomy have similar prognosis, but segmentectomy has advantages with less injury and faster recovery over lobectomy.
ObjectiveTo explore the risk factors for lymph node metastasis in patients with T2 stage non-small cell lung cancer.MethodsThe clinical data of 271 patients with non-small cell lung cancer who underwent surgical treatment in our hospital from 2014 to 2017 were collected, including 179 males and 92 females, with an average age of 62.73±0.58 years. The patients were divided into N0, N1, and N2 groups according to the lymph node metastasis status. The clinical data of the patients in different groups were compared.ResultsThe body mass index (BMI, P=0.043), preoperative lymph node enlargement (P<0.001), and tumor diameter (P<0.001) were significantly different among groups. The BMI (OR=1.131, 95%CI 1.001-1.277, P=0.048) and preoperative lymph node enlargement (OR=3.498, 95%CI 1.666-7.342, P=0.001) were independent risk factors for N2 lymph node metastasis, and tumor diameter was an independent risk factor for both N1 (OR=1.538, 95%CI 1.067-2.218, P=0.021) and N2 (OR=1.814, 95%CI 1.196-2.752, P=0.005) lymph node metastasis.ConclusionPatients with high BMI or enlarged lymph nodes before surgery have a high risk for N2 lymph node metastasis, and those with large tumor diameter have a high risk for both N1 and N2 lymph node metastasis.