Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Identification of candidate genes for lung cancer somatic mutation test kits.

Over the past three decades, mortality from lung cancer has sharply and continuously increased in China, ascending to the first cause of death among all types of cancer. The ability to identify the actual sequence of gene mutations may help doctors determine which mutations lead to precancerous lesions and which produce invasive carcinomas, especially using next-generation sequencing (NGS) technology. In this study, we analyzed the latest lung cancer data in the COSMIC database, in order to find genomic "hotspots" that are frequently mutated in human lung cancer genomes. The results revealed that the most frequently mutated lung cancer genes are EGFR, KRAS and TP53. In recent years, EGFR and KRAS lung cancer test kits have been utilized for detecting lung cancer patients, but they presented many disadvantages, as they proved to be of low sensitivity, labor-intensive and time-consuming. In this study, we constructed a more complete catalogue of lung cancer mutation events including 145 mutated genes. With the genes of this list it may be feasible to develop a NGS kit for lung cancer mutation detection.

[Correlation analysis between imaging features and lymph node metastasis in T1a lung adenocarcinoma].

OBJECTIVE: To analyze the data of patients with clinical stage T1a lung adenocarcinoma and find the predictive factors associated with lymph node metastasis. METHODS: From January to June 2012, 271 patients with small nodules of peripheral lung adenocarcinoma were enrolled in the retrospective review. There were 105 male and 112 female patients, with an average age of (61 ± 11)years (range 32-85 years). The data were collected including age, gender, smoking history, carcinoembryonic antigen(CEA), imaging findings, surgical procedure, pleural involvement, symptoms, tumor size, pathological classification, pathologic stage, maximum standardized uptake value(SUVmax) and lymph node metastasis. The predictive factors of lymph node metastasis in clinical factors were detected by univariate and multivariate analysis. RESULTS: By preoperative thin-section CT, 35 patients were categorized as pure ground-grass opacity(GGO), 11 cases of atypical adenomatous hyperplasia, 24 cases of adenocarcinoma in situ, with no lymph node metastasis. Categorized as mixed ground-glass opacities in 89 patients, 84 patients (94.4%) had no lymph node metastasis, only 5 patients (6.0%) with lymph node metastasis. Categorized as solid nodules in 93 patients, a total of 28 cases (30.1%) had lymph node metastasis. There were statistically significant difference between three groups (χ(2) = 23.41, P < 0.001) . By univariate analysis, we found that the predictive factors of lymph node metastasis were as follows: tumor size > 1 cm (χ(2) = 9.021, P < 0.003) , imaging performance with mixed GGO or solid nodules (χ(2) = 23.41, P < 0.000) , CEA > 5 µg/L (χ(2) = 15.541, P < 0.000) and PET-CT SUVmax > 5 (χ(2) = 0.644, P < 0.000). By multivariate analysis, we found that imaging performance (mixed GGO or solid nodules) was the independent predictor of lymph node metastasis in clinical factors (OR = 166.116, 95%CI:18.161-25.19, P < 0.001) . CONCLUSIONS: Patients of pure GGO generally do not have lymph node metastasis. Tumor diameter > 1 cm, imaging findings with the mixed GGO or solid nodules, carcinoembryonic antigen CEA > 5 µg/L, PET-CT SUVmax > 5 are predictive factors of lymph node metastasis in which imaging is independent predictor.

Prognostic impact of vascular endothelial growth factor-A and E-cadherin expression in completely resected pathologic stage I non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to evaluate the value of vascular endothelial growth factor-A and E-cadherin expression as well as other confirmed prognostic factors in predicting the clinical outcome after definitive surgery of pathologic stage I non-small cell lung cancer. METHODS: One hundred and eighty-five consecutive and non-selected patients who underwent definitive surgery for stage I non-small cell lung cancer in our institute were included in this study. Formalin-fixed paraffin-embedded specimens were stained for vascular endothelial growth factor-A and E-cadherin and the correlation between the staining, its clinicopathological parameters and its prognostic power were analyzed statistically. RESULTS: Of the 185 patients studied, 92 cases (49.7%) were strongly positive for vascular endothelial growth factor-A. Vascular endothelial growth factor-A expression was only related to visceral pleural involvement (P < 0.001). A total of 95 carcinomas (51.4%) were E-cadherin-negative tumors. E-cadherin expression correlated with histology (P < 0.001), tumor size (P = 0.001) and visceral pleural involvement (P < 0.001). In univariate analysis by log-rank test, gender, tumor size, lymphovascular invasion, visceral pleural involvement, vascular endothelial growth factor-A expression and E-cadherin expression were significant prognostic factors (P = 0.003, 0.042, 0.026, 0.035, 0.008 and 0.006, respectively). In multivariate analysis, gender, vascular endothelial growth factor-A and E-cadherin expression maintained its independent prognostic influence on overall survival (P = 0.013, <0.001 and 0.036, respectively). CONCLUSIONS: Expression of vascular endothelial growth factor-A is related to visceral pleural involvement, and E-cadherin expression correlates with histology, tumor size and visceral pleural involvement. Multivariate analysis confirmed gender, vascular endothelial growth factor-A and E-cadherin expression were significant predictive factors for overall survival in completely resected pathologic stage I non-small cell lung cancer.

G-MDSCs-Derived Exosomal miRNA-143-3p Promotes Proliferation via Targeting of ITM2B in Lung Cancer.

BACKGROUND: The immune environment of lung cancer is complex, and the critical immune factors that promote lung cancer progression need to be explored. Granulocytic myeloid-derived suppressor cells (G-MDSCs) are regarded as immune suppressing cells. However, they also promote tumor progression through other ways, which needs to be explored further. Therefore, we sought to study the regulatory mechanisms underlying the cancer promoting function of G-MDSCs in lung cancer. METHODS: G-MDSCs were isolated from lung cancer tissues using flow cytometry. Exosomes were separated from the G-MDSCs supernatant by ultracentrifugation and verified using flow cytometry, Western blot, and transmission electron microscopy (TEM). RNA sequencing was used to identify the differential miRNAs and genes. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results. The proliferation rate was assessed using the CCK-8 assay. Lentiviral vectors were used to alter the expression of the miRNAs and genes to analyze their effects on lung cancer progression. RESULTS: G-MDSCs secreted more exosomes in the lung cancer tissues, which promoted cancer progression by accelerating proliferation. Micro RNA-143-3p (miR-143-3p) increased in G-MDSCs derived exosomes and downregulated integral membrane protein 2B (ITM2B) by targeting the 3'-untranslated region (UTR) region. Overexpression of miR-143-3p enhanced proliferation by inhibiting transcription of ITM2B to activate the PI3K/Akt signaling pathway, which can be blocked by deguelin. This phenomenon was further confirmed by accelerated tumor growth and worse prognosis in mice. CONCLUSION: The key findings of this study highlight the potential of the G-MDSC-derived exosomes and the miR-143-3p/ITM2B axis as therapeutic targets and clinical indicators of lung cancer.

[VEGF-C mRNA expression and its relationship with clinicopathological parameters in esophageal squamous cell carcinoma].

OBJECTIVE: To detect the expression of VEGF-C mRNA and to investigate its relationship with clinicopathological parameters in esophageal squamous cell carcinoma (ESCC). METHODS: Real-time quantitative reverse transcriptase-PCR was used to measure the level of VEGF-C mRNA in the tumor tissue and corresponding normal mucosa in ESCC patients. RESULTS: The VEGF-C mRNA expression in tumor tissue was significantly higher than that in the corresponding normal mucosa (6.30 vs. 2.81, P = 0.02), and also significantly higher in the patients with lymph node metastasis than that in those without lymph node metastasis (10.11 vs. 4.15, P = 0.04). Among the patients with metastatic lymph nodes, VEGF-C mRNA expression was 62.19 in the patients with > or = 4 metastatic lymph nodes versus 6.30 in those with < 4 (P = 0.01), and 18.98 in the patients with > or = 3 metastatic lymph node stations versus 4.92 in those with < 3 (P = 0.04). In terms of stage, VEGF-C mRNA expression was significantly higher in the stage II b + III + IV than that in the stage I + II a (9.99 vs. 3.80, P = 0.03). Logistic binary regression analysis showed that VEGF-C mRNA was an independent risk factor for lymph node metastasis in ESCC (P = 0.01). In survival analysis, 2-year survival rate was not related with VEGF-C mRNA expression (P = 0.46). It was showed by COX regression model that the number of metastatic lymph node stations was the only independent risk factor for survival (P < 0.01). CONCLUSION: The expression of VEGF-C mRNA play an important role in lymph node metastasis of human ESCC.

Clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare form of non-small cell lung carcinoma. The current study focused on its clinicopathological features and potential factors influencing the prognosis. METHODS: The statistical analysis was based on the clinicopathological records and the prognosis of 43 LELC patients, analyzed by Kaplan-Meier method, Log-rank test, and COX regression analysis. RESULTS: The patients' average age was 57.35±9.22 years, 86.05% of them were non-smokers and 53.49% were women. The average tumor diameter was 3.24±1.57 cm. The 2- and 5-year overall survival (OS) rates of LELC patients were 90% and 74%, respectively; the disease-free survival (DFS) rates were 87% and 47%, respectively. The patients with large tumor, accompanied with lymph nodes metastasis or at the advanced stage had the worst OS, and the patients with lymph nodes metastasis or at the advanced stage had the worst DFS. Univariate analysis indicated that T and N grading and TNM stage influenced the OS, and N grading and TNM stage influenced the DFS; the independent factors affecting OS or DFS were not identified by multivariate analysis. CONCLUSIONS: LELC commonly occurred in senior non-smoking women. In summary, the prognosis of LELC was satisfactory.

Expression of GPC3 protein and its significance in lung squamous cell carcinoma.

The purpose of this study was to investigate GPC3 gene expression in lung squamous cell carcinoma tissue and its correlation with clinical and tumor characteristics. Using RT-PCR, the presence of GPC3 gene expression was detected in cancer tissue and adjacent normal tissue in 66 cases of lung squamous cell carcinoma and positive rates were calculated. Using Western blot, changes in GPC3 protein expression were detected in lung squamous cell carcinoma and adjacent normal tissues. The percentage of tissue samples expressing GPC3 mRNA was significantly higher in lung squamous cell carcinoma than in adjacent normal tissue (P < 0.05). This percentage was also significantly higher for cases with lymph node metastasis than for those without lymph node metastasis (P < 0.05). Further, the percentage of samples expressing GPC3 mRNA was higher with lowering degrees of tumor differentiation (P < 0.05). Rates of GPC3 expression were, however, independent of patient gender, age, and tumor size (P > 0.05). The expression of GPC3 protein in lung squamous cell carcinoma was significantly higher than that in adjacent normal tissues (P < 0.05). The expression in cases with lymph node metastasis was significantly higher than in those without lymph node metastasis (P < 0.05), and GPC3 protein expression increased with lowering degrees of tumor differentiation (P < 0.05). Further investigation is warranted for the association of initiation, development, invasion, and metastasis of disease.

A classification method based on principal components of SELDI spectra to diagnose of lung adenocarcinoma.

PURPOSE: Lung cancer is the leading cause of cancer death worldwide, but techniques for effective early diagnosis are still lacking. Proteomics technology has been applied extensively to the study of the proteins involved in carcinogenesis. In this paper, a classification method was developed based on principal components of surface-enhanced laser desorption/ionization (SELDI) spectral data. This method was applied to SELDI spectral data from 71 lung adenocarcinoma patients and 24 healthy individuals. Unlike other peak-selection-based methods, this method takes each spectrum as a unity. The aim of this paper was to demonstrate that this unity-based classification method is more robust and powerful as a method of diagnosis than peak-selection-based methods. RESULTS: The results showed that this classification method, which is based on principal components, has outstanding performance with respect to distinguishing lung adenocarcinoma patients from normal individuals. Through leaving-one-out, 19-fold, 5-fold and 2-fold cross-validation studies, we found that this classification method based on principal components completely outperforms peak-selection-based methods, such as decision tree, classification and regression tree, support vector machine, and linear discriminant analysis. CONCLUSIONS AND CLINICAL RELEVANCE: The classification method based on principal components of SELDI spectral data is a robust and powerful means of diagnosing lung adenocarcinoma. We assert that the high efficiency of this classification method renders it feasible for large-scale clinical use.

Can ¹8F-fluorodeoxyglucose positron emission tomography predict responses to neoadjuvant therapy in oesophageal cancer patients? A meta-analysis.

OBJECTIVES: Neoadjuvant therapy for the treatment of oesophageal cancer was introduced in an effort to improve prognosis. Response assessment is crucial for the treatment of patients with oesophageal cancer. Currently, ¹8F-fluorodeoxyglucose positron emission tomography (¹8F-FDG PET) seems to be the best available tool to assess neoadjuvant therapy response in patients with oesophageal cancer. The purpose of this study was to assess the diagnostic value of ¹8F-FDG PET for the evaluation of neoadjuvant therapy responses in patients with oesophageal cancer using a meta-analysis. A unified procedure and evaluation standard for ¹8F-FDG PET in the assessment of neoadjuvant therapy response should be established. METHODS: All published English-language studies pertaining to the assessment of neoadjuvant therapy response in patients with oesophageal cancer using ¹8F-FDG PET in the MEDLINE and EMBASE databases were collected. The methodological quality of the included studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. Pooled sensitivity, specificity, diagnostic odds ratios and summary receiver operating characteristic curves were obtained using statistical software. RESULTS: Thirteen studies included in the meta-analysis fulfilled the inclusion criteria of the Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. The pooled sensitivity, specificity and diagnostic odds ratios for F-¹8FDG PET in the evaluation of neoadjuvant therapy response in patients with oesophageal cancer were 70.3% [95% confidence interval (CI): 64.4-75.8], 70.1% (95% CI: 65.1-74.8) and 9.389 (95% CI: 3.482-25.319), respectively. The area under the curve and the Q value for the summary receiver operating characteristic curve were 0.8244 and 0.7575, respectively. CONCLUSION: ¹8F-FDG PET has some value in the assessment of neoadjuvant therapy response in patients with oesophageal cancer. A 50% reduction in standardized uptake value between pretherapy and posttherapy positron emission tomography scans performed in the first 2 weeks after the initiation of neoadjuvant therapy is the optimal condition for predicting a response to neoadjuvant therapy in patients with oesophageal cancer.