Survival Outcomes of Sublobectomy and Lobectomy in Elderly Patients with Peripheral Solid-Dominant Non-small Cell Lung Cancer.

BACKGROUND: According to the JCOG0802 study, there were many non-cancer-related deaths in the lobectomy group. Meanwhile, the median age of the enrolled patients in the JCOG0802 study was 67 years old. Whether this difference in perioperative outcomes and survival outcomes is related to age remains unknown. We aim to investigate whether the sublobectomy was comparable to lobectomy in elderly (≥ 75 years old) patients with peripheral solid-dominant [50% ≤ consolidation tumor ratio (CTR) ≤ 1] and diameter ≤ 2 cm non-small cell lung cancer (NSCLC). METHODS: We retrospectively included 10,830 patients who underwent surgery treatment at two large-volume medical centers, Taizhou Hospital of Zhejiang Province and Shanghai Chest Hospital, from January 2016 to January 2018. Of these, 164 patients aged ≥ 75 years, tumor ≤ 2 cm, and 50% ≤ CTR ≤ 1 who received lobectomy or sublobectomy were included in our study. The perioperative outcomes, survival analyses, analysis of death patterns, tumor recurrence patterns, and Cox regression analyses were performed. RESULTS: On perioperative outcomes, sublobectomy was associated with a shorter operation time (p < 0.001), and in terms of survival outcomes, the 5-year overall survival (OS, p = 0.85) and 5-year disease-free surivial (DFS, p = 0.58) did not differ significantly between the two groups. The Cox regression analyses showed that CTR value, visceral pleural infiltration, and smoking were independent risk factors for worse OS. Furthermore, tumor recurrence pattern and death patterns between the two groups did not differ significantly. CONCLUSIONS: Sublobectomy could achieve superior perioperative outcomes and equivalent oncological efficacy in comparison with lobectomy in elderly patients (≥ 75 years old) with peripheral solid-dominant and diameter ≤ 2 cm NSCLC.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

The role of ferroptosis in esophageal cancer.

Esophageal cancer is one of the most common cancers with high mortality rate around the world. Although the treatment strategy of this disease has made great progress, the prognosis of advanced patients is not ideal. Ferroptosis, a novel regulatory cell death model, that is different from traditional apoptosis and characterized by increased Fenton reaction mediated by intracellular free iron and lipid peroxidation of cell membrane. Ferroptosis has been proved to be closely linked to a variety of diseases, especially cancer. This review aims to summarize the core mechanism of ferroptosis in esophageal cancer, the regulation of ferroptosis signaling pathway and its current application. At the same time, we emphasize the potential and prospect of ferroptosis in the treatment of esophageal cancer. Collectively, targeting ferroptosis pathway may provide new insights into the diagnosis, treatment and prognosis of esophageal cancer.

(Neo)adjuvant Chemoradiotherapy is Beneficial to the Long-term Survival of Locally Advanced Esophageal Squamous Cell Carcinoma: A Network Meta-analysis.

PURPOSE: To determine the most effective and safest treatment mode for locally advanced resectable esophageal squamous cell carcinoma through a network meta-analysis. METHOD: A Bayesian model was used for a network meta-analysis comparing the efficacy and safety of surgery alone, neoadjuvant therapy, and adjuvant therapy. RESULTS: Thirty clinical studies, including thirty-one articles, 4866 patients, were analyzed. Overall survival rate: Adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy were significantly advantageous over surgery alone [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.93; HR 0.75, 95%CI 0.65-0.86]. There was no statistically significant difference between adjuvant chemoradiotherapy and neoadjuvant chemoradiotherapy [HR 0.97, 95%CI 0.75-1.28]. Disease-free survival rate: Compared with surgery alone, neoadjuvant chemoradiotherapy had significant benefits [HR 0.65, 95%CI 0.53-0.78]; adjuvant chemoradiotherapy had similar, but not significant benefits [HR 0.7, 0.95%CI 0.45-1.06]. The difference between neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy was also not statistically significant [HR 0.94, 0.95%CI 0.61-1.43]. Surgery after neoadjuvant chemoradiotherapy: The R0 resection rate was significantly improved [relative risk (RR) 0.25, 95%CI 0.07-0.86], but the overall postoperative morbidity rate and 30-day postoperative mortality rate tended to increase [RR 1.27, 95%CI 0.8-2.01; RR 1.59, 95%CI 0.7-3.22]. Neither neoadjuvant chemotherapy nor neoadjuvant radiotherapy significantly altered the surgical safety or R0 resection rate. CONCLUSION: Both neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy appear to be the best supplements to surgery for locally advanced resectable esophageal squamous cell carcinoma.

The expression of miRNA-216b is negatively correlated with 18F-FDG uptake in non-small cell lung cancer.

BACKGROUND: This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC. METHODS: Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC. RESULTS: Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC. CONCLUSION: miRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.

Effects of dietary yeast culture on shrimp growth, immune response, intestinal health and disease resistance against Vibrio harveyi.

The current study was conducted to evaluate the effects of different levels of yeast culture (YC) supplementation at 0% (YC 0%), 1% (YC 1%), and 2% (YC 2%) on growth, feed conversion ratio, body composition, intestinal morphology, microflora, immune response, and resistance to Vibrio harveyi infection in Litopenaeus vannamei. After 8-weeks feeding trial, the results showed significant improvement (p < .05) in the final weight, weight gain rate, specific growth rate, survival rate and low feed conversion ratio in YC groups than the control. Serum total protein, superoxide dismutase, catalase, alkaline phosphatase, acid phosphatase, lysozyme, and phenol oxidase in shrimps fed diet YC (2%) were significantly higher (p < .05), whereas significantly decreased trend in serum cholesterol, triglyceride, aspartate aminotransferase, and alanine aminotransferase (p < .05) were observed in YC (2%) diet. Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes were the core phylum bacteria found in the shrimp intestines. At the genus level, opportunistic pathogenic bacteria, Vibrio was significantly decreased (p < .05) while beneficial bacteria Pseudoalteromonas was increased in YC (2%) group. Intestinal villus height and width in shrimps fed YC diets were significantly improved than the control diet (p < .05). YC groups challenged test significantly showed (p < .05) improved shrimps immune response against V. harveyi infections with YC (2%) recording the highest percentage survival rate (70%). The present study demonstrated that supplementing YC (2%) can improve growth, intestinal microbiota, intestinal morphology, and immune response against V. harveyi infections in L. vannamei.

Thoracoscopic Treatment of Giant Pulmonary Bullae.

BACKGROUND: Giant pulmonary bullae (GPB) is rare. The aim of this study was to evaluate the functional results of video-assisted thoracic surgery (VATS) in the treatment of GPB and the factors associated with complications following VATS resection for GPB. MATERIALS AND METHODS: From January 2010 to January 2015, 44 GPB patients underwent surgery with VATS. Individual GPB patient characteristics and surgical outcomes were evaluated. The patients were separated into two groups (an emphysematous group and a nonemphysematous group), and differences between the respective groups were investigated. RESULTS: Although there were no mortalities within a 30-d postoperative period among the 44 GPB patients treated surgically with VATS, 28 experienced postoperative complications, of which the most common were air leaks. VATS for GPB resulted in obvious improvements in symptoms and lung function in the majority of cases. Among 26 patients with preoperative dyspnea, the symptoms of 22 patients (84.62%) improved after treatment with VATS resection for GPB, and the mean forced expiratory volume in 1 s increased from 2.24 L preoperatively to 2.5 L postoperatively (P = 0.02). The complication rate of patients aged >48 y, who smoked and had emphysema, was significantly higher than that of those who did not smoke and did not have emphysema (79.2% versus 45%, P = 0.019; 85.7% versus 25%, P < 0.05; 88% versus 31.6%, P < 0.05). These characteristics could be associated with complications. CONCLUSIONS: VATS resection is a safe and effective treatment for GPB and leads to improvements in symptoms and lung function. Patients >48 y, who smoked and had emphysema, were more likely to experience postoperative complications. There could be a relationship between these characteristics and the patients' postoperative complications.

Preparation, Mechanical Properties, and Biocompatibility of Graphene Oxide-Reinforced Chitin Monofilament Absorbable Surgical Sutures.

Chitin (CT) is a good material to prepare surgical sutures due to its conspicuous biological characteristics. However, the poor mechanical strength of pure CT sutures limits its application. In order to improve its strength, a composite monofilament absorbable suture was prepared in this study using graphene oxide and chitin (GO-CT) using a green method. FT-IR spectra showed that GO-CT contained the characteristic functional groups of GO and CT, indicating that a GO-CT suture was successfully obtained. With the addition of a small amount of GO (1.6wt% solution) in chitin, the breaking tensile strength, knot strength, and knot-pull strength of the GO-CT suture were significantly improved compared to the CT suture. The biocompatibility of the GO-CT suture in vitro was checked by tetrazolium-based colorimetric assays and no cytotoxicity to L929 cells was found. In vivo, the subcutaneous implantation of GO-CT sutures in the dorsal skin of rats found no abnormalities by hematoxylin-eosin staining. Furthermore, there were no significant changes in the gene expression of the inflammatory mediators, interleukin 1ß (IL-1ß), tumor necrosis factor-α, IL-6, IL-17A, interferon-γ, or IL-10; however, the expression of transforming growth factor ß was significantly increased in the first week. In summary, GO-CT sutures may have potential as a suture material in the clinic.

Prognosis of primary tracheal tumor: A population-based analysis.

BACKGROUND: To elucidate the survival outcomes of tracheal tumors and to propose the potential stage of tracheal tumors. METHOD: All cases of primary tracheal malignant tumors were extracted from the Surveillance, Epidemiology, and End Results database (SEER) during 1973-2013. The overall survival was calculated using Kaplan-Meier method. Cox regression was utilized to identify the prognostic factors. RESULT: A total of 287 cases were finally included. The median age of the patients was 59 years. Male patients accounted for 56.1%. The median survival was 57 months. Patients were categorized as Extension1 to 4 (E1-4) and N0-N3. E1 group with size <4 cm had the best prognosis. While E1 >4 cm, E2 and E3 <3 cm groups had similar outcomes, which were superior to E3 >3 cm group. E4 was the worst. N0 patients had ideal prognosis, which were better than N1 and N2 patients. The 3-year survival rates of each T category were 74.7%, 57.3%, 28.1%, and 9.1%, respectively. In multivariate analysis, age, histology, tumor size, and extension were independent prognostic factors. CONCLUSION: Patients with old age, large tumor size, advanced extension or no surgery may have worse prognosis. The proposed T category of tracheal tumor incorporating tumor extension and size helped to predict survival outcomes.

Identification of Biomarkers for Lung Adenocarcinoma With Qi Deficiency and Phlegm Dampness.

BACKGROUND: Qi deficiency and phlegm dampness (QPD) is one of the most common traditional Chinese medicine (TCM) syndromes in lung adenocarcinoma (LUAD). This study aimed to identify syndrome-specific biomarkers for LUAD with QPD syndrome. METHODS: Peripheral blood mononuclear cells (PBMCs) from LUAD patients with QPD, LUAD patients with non-QPD (N-QPD), and healthy control (H) were collected and analyzed with RNA-seq to identify differentially expressed genes (DEGs). The area under the receiver operator characteristic curve (AUC) of each DEG was calculated, and the top 10 highest AUC DEGs were validated by qRT-PCR. Logistic regression analysis was used to develop a diagnostic model evaluated with AUC. RESULTS: A total of 135 individuals were enrolled in this study (training set: 15 QPD, 15 N-QPD, 15 H; validation set: 30 QPD, 30 N-QPD, 30 H). A total of 1480 DEGs were identified between QPD and N-QPD. The qRT-PCR results showed that the expression of DDR2 was downregulated, and PPARG was upregulated, which was in line with the finding of the training set. We developed a diagnostic model with these two genes. The AUC of the diagnostic model in the training cohort and validation cohort was 0.891 and 0.777, respectively. CONCLUSIONS: We identified the two genes (DDR2 and PPARG) as syndrome-specific biomarkers for LUAD with QPD syndrome and developed a novel diagnostic model, which may help to improve the accuracy and sensibility of clinical diagnosis and provide a new target for natural drug treatment of LUAD.

ZNF468-mediated epigenetic upregulation of VEGF-C facilitates lymphangiogenesis and lymphatic metastasis in ESCC via PI3K/Akt and ERK1/2 signaling pathways.

PURPOSE: Dysfunctional lymphangiogenesis is pivotal for various pathological processes including tumor lymph node metastasis which is a crucial cause of therapeutic failure for ESCC. In this study, we aim to elucidate the molecular mechanisms and clinical relevance of Zinc-finger protein ZNF468 in lymphangiogenesis and lymphatic metastasis in ESCC. METHODS: Immunohistochemistry, Western blot, Kaplan-Meier plotter analysis and Gene Set Enrichment Analysis were preformed to detect the association of ZNF468 with lymphangiogenesis and poor prognosis in ESCC patients. Foot-pads lymph node metastasis model, tube formation assay, 3D-culture assay and invasion assay were preformed to verify the effect of ZNF468 on lymphangiogenesis and lymph node metastasis. CUT&Tag analysis, immunoprecipitation and mass spectrometry analysis and ChIP-PCR assay were preformed to study the molecular mechanisms of ZNF468 in lymphangiogenesis. RESULTS: We found that ectopic expression of ZNF468 was correlated with higher microlymphatic vessel density in ESCC tissues, leading to poorer prognosis of ESCC patients. ZNF468 enhanced the capacity of lymphangiogenesis and promoted lymphatic metastasis in ESCC both in vitro and in vivo. However, silencing ZNF468 reversed these phenotypes in ESCC. Mechanically, we demonstrated that ZNF468 recruits the histone modification factors (PRMT1/HAT1) to increase the levels of H4R2me2a and H3K9ac, which then leads to the recruitment of the transcription initiation complex on the VEGF-C promoter, ultimately promoting the upregulation of VEGF-C transcription. Strikingly, the promoting effect of lymphatic metastasis induced by ZNF468 in ESCC was abrogated by targeting PRMT1 using Arginine methyltransferase inhibitor-1 or silencing VEGF-C. Furthermore, we found that the activation of PI3K/AKT and ERK1/2 signaling is required for ZNF468-medicated lymphatic metastasis in ESCC. Importantly, the clinical relevance between ZNF468 and VEGF-C were confirmed not only in ESCC samples and but also in multiple cancer types. CONCLUSION: Our results identified a precise mechanism underlying ZNF468-induced epigenetic upregulation of VEGF-C in facilitating lymphangiogenesis and lymph node metastasis of ESCC, which might provide a novel prognostic biomarker and potential therapeutic for ESCC patients.

Expression of gamma-aminobutyric acid receptors on neoplastic growth and prediction of prognosis in non-small cell lung cancer.

BACKGROUND: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the adult mammalian brain, but exerts physiologic effects other than that on neurotransmitter in non-neuronal peripheral tissues and organs. GABA may affect cancer growth through activation GABA receptors. We investigated the gene expression of GABA receptors in tissue of non-small cell lung cancers (NSCLC) and non-cancerous tissues, and found that the gene expression of GABA receptor phenotypes was correlated with tumorigenesis and clinical prognosis. METHODS: Sixty-one snap-frozen human samples of NSCLC tissues and paired non-cancerous tissues (5cm away from tumor) were analyzed. Gene expression of GABA receptors was detected by Real-time quantitative PCR (RT-qPCR). Survival times in relation to the expression of GABA receptor phenotypes were analyzed. Human NSCLC cell lines H1299, A549, H520, H460 and human bronchial epithelial cell line BEAS-2B were used to determine the phenotypes of GABA inhibitory effects on cancer cell growth. The effects of exogenous administration of GABA on H1299 cell growth were examined. RESULTS: The gene expressions were significantly higher in NSCLC tissues than in the paired non-cancerous tissues for GABAA receptor subunit α3 (GABR(A3), P = 0.030); for GABAA receptor subunit epsilon (GABRE, P = 0.036); and GABAB receptor subunit 2 (GABBR2, P = 0.005). Kaplan-Meier curves showed that patients with high expression of GABBR2 gene and low expression of GABR(A3 )gene had a better prognosis (P < 0.05). The administration of GABA resulted in suppressed proliferation of NSCLC cell lines in a dose- and time-dependent manner. The use of the GABA receptor antagonist CGP35348 could reverse the inhibitory effect. CONCLUSIONS: The pattern of GABA receptor gene phenotype expression may be involved in the regulation of tumorigenesis. A high expression of GABBR2 with a low expression of GABR(A3) may predict a better outcome. The treatment with GABA attenuates cancer cell growth in vitro. The expression of GABA receptor may be not only promising genetic therapeutic targets but may also serve as valuable prognostic markers for NSCLC.

Effect of preoperative radiotherapy on the prognosis of patients with stage cTxN0M0 esophageal squamous cell carcinoma: propensity score matching analysis based on SEER database.

Objective: The aim of this study was to investigate the effect of preoperative radiotherapy (RT) on overall survival (OS) in patients with stage cTxN0M0 esophageal squamous cell carcinoma (ESCC). Methods: A total of 467 patients with ESCC diagnosed as cTxN0M0 and undergoing esophagectomy between 2004 and 2016 were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. According to the presence or absence of preoperative RT, the patients were divided into preoperative RT group and non-preoperative RT group. Propensity score matching (PSM) was performed to equalize baseline levels between groups. Univariate and multivariate Cox regression analyses were used to compare the survival differences between the two groups. Results: Using PSM, 162 pairs of patients were selected. Preoperative RT was not a prognostic factor for OS in all patients with cTx stage. After PSM, for patients with cT1-2 stage, univariate Cox regression analysis showed that preoperative RT was an influencing factor of OS, and multivariate Cox regression analysis confirmed that preoperative RT was an independent predictor of OS. Compared with non-preoperative RT, preoperative RT significantly decreased OS (HR = 1.556, 95%CI 1.008-2.464, p = 0.046). For patients with cT3-4, univariate Cox regression analysis showed that preoperative RT was an influencing factor for OS, and multivariate Cox regression analysis determined that preoperative RT was independent predictors of survival. Compared with non-preoperative RT, preoperative RT significantly improved the OS (HR = 0.479, 95%CI 0.272-0.841, p = 0.010). Conclusion: For ESCC, preoperative RT can improve the OS of patients with cT3-4N0M0. However, preoperative RT is not suitable for patients with cT1-2N0M0.

Effects of Carbohydrase Supplementation on Growth Performance, Intestinal Digestive Enzymes and Flora, Glucose Metabolism Enzymes, and glut2 Gene Expression of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) Fed Different CHO/L Ratio Diets.

An optimal carbohydrate-to-lipid (CHO: L) ratio facilitates fish growth and protein conservation, and carbohydrase promotes nutrient absorption. Therefore, an 8-week feeding trial was conducted to investigate the effects of carbohydrase supplementation on growth performance, intestinal digestive enzymes and flora, glucose metabolism enzymes and glut2 gene expression in juvenile hybrid grouper (Epinephelus fuscoguttatusâ™€× Epinephelus lanceolatus♂) fed different CHO: L ratios diets. L, M, and H represent CHO:L ratios of 0.91, 1.92 and 3.91, respectively. LE, ME, and HE represent CHO:L ratios of 0.91, 1.92, 3.91, respectively, supplemented with the same ratio of carbohydrase. Results showed that weight gain rate (WGR) and specific growth rate (SGR) reached a maximum in group M and were significantly enhanced by carbohydrase (p < 0.05). Crude lipid content decreased significantly with an increase in the dietary CHO:L ratio (p < 0.05). Significant increases in the trypsin (TRY) and amylase (AMS) activities and significant decreases in the lipase (LPS) activity were observed with increasing dietary CHO:L ratio, and the former two were significantly promoted by carbohydrase (p < 0.05). The content of liver and muscle glycogen increased significantly with the increasing dietary CHO:L ratio but decreased significantly after carbohydrase supplementation (p < 0.05). The glucokinase (GK), pyruvate kinase (PK), Phosphate 6 fructokinase-1 (PFK-1) and phosphoenolpyruvate kinase (PEPCK) activities increased significantly with increasing dietary CHO:L ratio (p < 0.05). Glut2 mRNA expression decreased significantly in liver and increased significantly in intestine with increasing dietary CHO:L ratio (p < 0.05). By linear discriminant analysis (LDA), the abundance of Alistipe was significantly higher in Group ME than in Group M. These results suggested that hybrid grouper can only moderately utilize dietary carbohydrate and lipid in diet, and a certain amount of high glycemic lipids occurred when fed with high-carbohydrate diets. By the weight gain for basis, the supplementation of carbohydrase in Group H with amylase, glycosylase, and pullulanase in a 1:1:1 ratio effectively lowered glycemic lipids, promoted the growth of grouper, digestive enzymes activities and carbohydrate metabolic enzyme, and glut2 gene expression in intestine, effectively balancing the negative effects of high-carbohydrate diet and improving the utilization of carbohydrate.

Neoadjuvant Immunotherapy in Oncogene-Positive Non-Small Cell Lung Cancer: A Multicenter Study.

BACKGROUND: Preoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown. METHODS: Data were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients' oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status. RESULTS: Overall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23). CONCLUSIONS: Patients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy.

Aberrant expression of miR-33a-3p/IGF2 in postmenopausal osteoporosis patients and its role and mechanism in osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP), the most frequent bone-related disease, is characterized by bone loss and fragile fractures, which is related to low bone density (BMD). This study aimed to illustrate the expression and mechanism of miR-33a-3p in osteoporosis. METHODS: TargetScan and luciferase reporter assay were applied for verifying the relevance between miR-33a-3p and IGF2. Levels of miR-33a-3p, IGF2, Runx2, ALP and Osterix were checked using RT-qPCR and western blotting. hBMSCs proliferation, apoptosis and ALP activity were analyzed by MTT, flow cytometry (FCM) analysis and ALP detection kit, respectively. Moreover, the calcification of cells was assessed using Alizarin Red S staining. The average BMD was evaluated by dual-energy X-ray absorptiometry (DEXA) assay. RESULTS: IGF2 was a target of miR-33a-3p. The level of miR-33a-3p was substantially higher and IGF2 expression was memorably lower in the serum of osteoporosis patients than that in healthy volunteers. Our results also pointed out that miR-33a-3p was reduced and IGF2 expression was enhanced during osteogenic differentiation. We concluded that miR-33a-3p negatively regulated the level of IGF2 in hBMSCs. Besides, miR-33a-3p mimic inhibited the osteogenic differentiation of hBMSCs via inhibiting the level of Runx2, ALP and Osterix and decreasing ALP activity. IGF2 plasmid dramatically reversed the influence of miR-33a-3p mimic on IGF2 expression, hBMSCs proliferation and apoptosis, and osteogenic differentiation of hBMSCs. CONCLUSION: miR-33a-3p affected osteogenic differentiation of hBMSCs by targeting IGF2, indicating a potential use of miR-33a-3p as plasma biomarker and therapeutic target for postmenopausal osteoporosis.

Prognostic impact of tumor spread through air spaces for T2aN0 stage IB non-small cell lung cancer.

BACKGROUND: Spread through air spaces (STAS) is a pattern of invasion recently identified in non-small cell lung cancer (NSCLC), with a poor prognosis. However, the predictive impact of STAS in stage IB NSCLC is not well understood. This investigation aims to assess the prognostic influence of STAS in stage IB NSCLC. METHODS: We reviewed 130 resected stage IB NSCLC between 2010 and 2015. Beyond the central tumor edge, lung parenchymal air gaps containing cancer cells were identified as STAS. In order to estimate recurrence-free survival (RFS) and overall survival (OS), Cox models and Kaplan-Meier techniques were utilized. Logistic regression analysis was employed to define the factors influencing STAS. RESULTS: Of 130 patients, 72 (55.4%) had STAS. STAS was a significant prognosticator. Kaplan-Meier method showed that STAS-positive patients had a significantly lower OS and RFS than STAS-negative patients (5-year OS, 66.5% vs. 90.4%, p = 0.02; 5-year RFS, 59.5% vs. 89.7%, p = 0.004) In a semiquantitative assessment, the RFS and OS were shorter in survival analysis when STAS increased (5-year RFS, 89.7%, no STAS, 61.8%, low STAS, 57.2%, high STAS, p = 0.013; 5-year OS, 90.4%, no STAS, 78.3%, low STAS, 57.2%, high STAS, p = 0.002). The association between STAS and poor differentiation, adenocarcinoma, and vascular invasion (p value was <0.001, 0.047, and 0.041, respectively) was statistically significant. CONCLUSIONS: The STAS is an aggressive pathological feature. RFS and OS could be significantly reduced by STAS, while it also serves as an independent predictor.