The efficacy of Raman spectroscopy in lung cancer diagnosis: the first diagnostic meta-analysis.

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion.

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient: A case report.

BACKGROUND: Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients, but the disseminated form of infection is rare among immunocompetent populations. The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma, leading to unnecessary open chest exploratory surgery, and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis. Positron emission tomography/computed tomography (PET/CT), a sensitive method for distinguishing malignant tumors, coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues. CASE: A 36-year-old man presented for general examination, without health complaints. Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value. Initially, we suspected primary malignancy with hematogenous metastasis. Although his routine fungal analysis had been negative, subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis. Fluconazole (200 mg/d) antifungal drug treatment was initiated, and 1 mo later the pulmonary mass had reduced in size markedly (on chest CT scan) without any complications. CONCLUSION: Serologic and PET/CT examinations may not rule out cryptococcosis, and percutaneous lung puncture is critical under all circumstances.

Correlation analysis between serum neuron-specific enolase and the detection of gene mutations in lung adenocarcinoma.

BACKGROUND: Lung cancer is a chronic, progressive and malignant disease associated with ever-growing incidence and mortality. Targeted therapy plays an important role in the clinical treatment of lung cancer. Besides, neuron-specific enolase (NSE), an intracellular enzyme, is highly correlated with the targeted treatment outcome in patients with non-small cell lung cancer (NSCLC). The present study aimed to explore the correlation of NSE with the detection of gene mutations. METHODS: It is a case-control study. From June 2017 to October 2019, the newly diagnosed patients with lung adenocarcinoma were enrolled from the First Affiliated Hospital of Anhui Medical University. Next-generation sequencing (NGS) was conducted in these patients. Kruskal-Wallis test was used to calculate the difference in NSE levels between mutant and non-mutant group and the differences were compared between blood and tissue samples. RESULTS: Compared with patients with no gene mutation (15.4±7.8 mmol/L), the NSE levels in patients with gene mutations were remarkably increased in blood sample group (22.2±12.9 mmol/L) (P<0.05). Besides, the linear regression model was applied for analysis which further emphasized the close relationship between them. The area under the ROC curve (AUC) of NSE was 0.7300 [95% confidence interval (CI): 0.6059-0.8541] and optimal threshold was 18.5650 U/mL with a sensitivity of 87.50% and a specificity of 52.08%. In addition, NSE levels increased in blood sample group, suggesting that the occurrence of polygenic mutation with dismal prognosis, but no correlation was detected in tissue sample group. CONCLUSIONS: This study elucidates the functional role of NSE, and findings in this study notably increase the gene detection efficiency for lung adenocarcinoma.

Cryptococcal pneumonia in a human immunodeficiency virus-negative patient: A case report.

BACKGROUND: Cases of cryptococcal pneumonia are frequently observed in patients with various innate or acquired immunodeficiencies, including organ transplant patients, cancer patients undergoing chemotherapy, patients with acquired immune deficiency syndrome, or patients on dialysis. Fluconazole is most often used to treat this condition when it is detected. CASE SUMMARY: In the present report, we describe the case of a 42-year-old human immunodeficiency virus-negative man with normal immune function who had cryptococcal pneumonia that was diagnosed after undergoing computed tomography-guided percutaneous lung puncture. We successfully treated this patient via administration of 200 mg voriconazole twice per day for 9 mo. CONCLUSION: This report provides evidence of the successful treatment of pulmonary cryptococcosis using voriconazole.

Successful steroid treatment for acute fibrinous and organizing pneumonia: A case report.

BACKGROUND: Since the acute fibrinous and organizing pneumonia (AFOP) was first described by Beasley in 2002, some case reports of patients aged from 38 d to 80 years have been published worldwide, but there is still no standard therapy for this disease and the treatment methods remain controversial. Both steroid and immunosuppressive agents, such as cyclophosphamide or mycophenolate mofetil, have been reported to be effective in some studies, but with many side effects, especially in patients of advanced age. CASE SUMMARY: We herein report an 81-year-old female patient who was admitted to our hospital due to dry cough, and breathlessness for 1 mo. She was treated with broad-spectrum antibiotics and anti-fungal therapy, but without improvement in both symptoms and radiological findings, and her respiratory status worsened, and she required bed rest almost the whole day. Computed tomography-guided percutaneous needle lung biopsy was performed and histopathology examination confirmed the diagnosis of AFOP. She was then successfully treated with a steroid monotherapy, which resulted in a satisfactory clinical outcome without serious complications. CONCLUSION: We conclude that complete remission of AFOP can be achieved by steroid monotherapy in patients of advanced age.

Specific inhibitor of Notch­3 enhances the sensitivity of NSCLC cells to gemcitabine.

Notch­3 is a receptor of the Notch signaling pathway and plays an important role in regulating self­renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch­3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non­small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N­[N­(3,5­difluorophenacetyl)­L­alanyl]­S­phenylglycine t­butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3). Both cell lines were subsequently treated with either DAPT or DAPT combined with GEM and then viability, apoptosis, colony formation and cell count assays were performed. DAPT treatment effectively downregulated the expression of NICD3 in both cell lines. DAPT combined with GEM also significantly reduced the percentage of viable cells in both cell lines, while increasing the percentage of apoptotic cells, compared with GEM alone. In the clonogenicity assays, the combination of DAPT and GEM led to a decrease in clone numbers and significantly greater inhibition of the H1299 and A549 cells compared to treatment with DAPT or GEM alone. Meanwhile, levels of the apoptosis­related proteins, Bcl­2 and Bax, were found to be affected by the various treatments. Thus Notch­3 appears to be a promising target for gene therapy and DAPT is able to mediate a strong antitumor effect in NSCLC cells that overexpress Notch­3. Further studies of a combined treatment regimen with DAPT and GEM are warranted and may provide greater efficacy and safety in the treatment of NSCLC patients.

Notch signaling molecules as prognostic biomarkers for non-small cell lung cancer.

Notch family proteins have been reported to be associated with the initiation and development of various types of tumors. The present study used a prospective design to investigate the role of Notch proteins as novel biomarkers that are capable of predicting the survival outcome for patients with non-small cell lung cancer (NSCLC). The protein expression of Notch 1, Notch 3 and their ligands, Jagged 1 and Delta-like 4, was examined using immunohistochemistry in NSCLC tissues and adjacent non-cancerous lung tissues from 101 patients who underwent surgical treatment. The expression was also correlated with clinicopathological parameters and overall survival (OS). High Notch 1 protein expression was observed in 55.4% (56/101) of NSCLC samples and high Notch 3 expression was observed in 53.5% (54/101). The nuclear expression of Notch 3 was significantly associated with the lymph node status (P=0.0026) and tumor-node-metastasis (TNM) stage (P<0.0001), while the coexpression of Notch 1 plus Notch 3 was associated with lymph node status (P=0.0056), TNM stage (P=0.0001) and the histological grading (P=0.0359). In the survival analyses, the high expression of Notch 1 and Notch 3 exhibited an additive effect toward a poorer OS compared with a subtype with low coexpression for the two proteins (P<0.001), with high nuclear Notch 3 expression in the NSCLC patients maintaining independent prognostic significance for the outcome on multivariate analysis. These data further demonstrate a central role for Notch signaling in NSCLC and the significance of Notch 3 as a prognostic indicator of a poorer survival for patients with resected NSCLC.

Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer.

Notch3 receptor is one of the mammalian Notch family receptors (Notch1-4) which plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis. Overexpression of Notch3 is associated with tumorigenesis. In order to assess the expression of Notch3 in Chinese non-small-cell lung cancer (NSCLC) patients and determine its association with prognosis, we designed a prospective study with five years of follow-up to evaluate Notch3 expression in NSCLC tissues and adjacent non-cancerous normal lung tissues from 131 patients undergoing surgical treatment by immunohistochemistry and western blot analysis. Notch3 had high expression in 67 of 131 cases of NSCLC (51.1 %), which was significantly higher than in adjacent noncancerous lung tissues. Moreover, Notch3 overexpression was significantly correlated with TNM stage (P = 5.41e-07 in squamous cell carcinoma, P = 5.338e-07 in adenocarcinoma) and lymph node metastasis (P = 0.00764 in squamous cell carcinoma, P = 0.01491 in adenocarcinoma). Kaplan-Meier survival analysis showed that the overall survival times in patients expressing Notch3 in NSCLC were shorter. Multivariate analysis further demonstrated that Notch3 was an independent prognostic factor for patients with NSCLC. Therefore, Notch3 might be a useful biomarker to predict the prognosis of patients with NSCLC.

CIP2A with survivin protein expressions in human non-small-cell lung cancer correlates with prognosis.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) and survivin are aberrantly expressed in a wide range of human cancers, including lung tumors. In order to assess the expressions of these two proteins in Chinese non-small-cell lung cancer (NSCLC) patients and determine their correlation with prognosis, NSCLC tissues and adjacent non-cancerous normal lung tissues were collected from 97 patients undergoing surgical treatment and evaluated by immunohistochemistry staining. CIP2A or survivin immunoreactivity was detected in significantly more NSCLC tissues than in adjacent non-cancerous lung tissues (P < 0.05). Moreover, CIP2A expression in NSCLC correlated with TNM stage, while survivin expression correlated with TNM stage and lymph node metastasis. Kaplan-Meier survival analysis showed that the overall survival times in patients expressing either CIP2A or survivin protein in NSCLC were shorter. COX regression analysis indicated that expression of CIP2A protein was an independent prognostic factor for NSCLC patients (HR = 3.631, P = 0.015). Therefore, CIP2A expression in Chinese NSCLC patients may be a useful biomarker of biological malignancy.

Increased expression of Toll-like receptors 4 and 9 in human lung cancer.

BACKGROUND: It has been reported lately that Toll-like receptors (TLRs) play an essential role in the activation of innate immunity, and TLRs are expressed in a large number of immune cells like B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells as well as epithelial cells. In the present study, we investigated whether there is a relationship between the expression of TLR4 or TLR9 and the clinical or pathological changes in human lung cancer. METHOD: Protein expression of TLR4 and TLR9 was assessed by using immunohistochemistry and western blotting. mRNA expressions of TLR4 and TLR9 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: High TLR4 and TLR9 mRNA signal intensity was found in the majority of lung cancer specimens. In contrast, tumor-free lung tissue showed lower signal intensity. Consistently, the low amount of TLR4 and TLR9 protein expression was found in tumor-free lung tissue, while they were strongly expressed in lung cancer tissue. In addition, we found for the first time that the differentiation degree of tumor cells was positively correlated with the expression level of TLR4. There was no relationship between the expressions of TLR4 or TLR9 and patients' age, gender, smoking, the histological type of tumor, lymph node metastasis, and tumor node metastases (TNM) stage. CONCLUSIONS: We found that both mRNA and protein levels of TLR4 and TLR9 were strongly expressed in lung cancer tissue. In addition, we reported for the first time a positive correlation between the expression level of TLR4 and malignancy of lung cancer. These results suggested that TLR4 and TLR9 may be involved in the development of lung cancer which may have the potentials for the treatment of this malignant tumor.

[Mechanism of regulation of leptin expression in human lung adenocarcinoma cells by hypoxia inducible factor-1alpha: a preliminary study].

OBJECTIVE: To investigate the regulation of leptin expression in human lung adenocarcinoma cells by hypoxia inducible factor-1 (HIF-1alpha) and the mechanism thereof. METHODS: Lung adenocarcinoma tissues were collected from 42 patients during operation and samples of corresponding adjacent lung tissue were obtained from 16 of the 42 specimens. The expression levels of HIF-1alpha and leptin were detected by immunohistochemical staining. Human lung adenocarcinoma cells of the line A549 cells were cultured for 0, 12, 24, and 48 h respectively, exposed to hypoxia induced by CoCl2. Other A549 cells were treated with GL331, a kind of HIF-1alpha inhibitor, of the concentrations of 0, 5, 10, or 20 micromol/L under normoxic condition for 24 h, and then were exposed to hypoxia induced by CoCl2 for 24 h. RT-PCR and Western-blotting were used to examine the mRNA and protein expression levels of HIF-1alpha and leptin in different groups. RESULTS: Immunohistochemistry showed that the positive rates of HIF-1alpha and leptin in the lung adenocarcinoma tissue were 57.1% and 69.0% respectively, both significantly higher than those in the adjacent normal lung tissues (18.8% and 25.0% respectively, both P<0.01). The protein expression levels of HIF-1alpha in the hypoxia 0, 12, 24, and 48 h groups were 0.314+/-0.030, 0.552+/-0.027, 0.743+/-0.015, and 0.799+/-0.010 respectively, and the protein expression levels of leptin were 0.398+/-0.016, 0.633+/-0.036, 0.796+/-0.008, and 0.942+/-0.088 respectively, increasing in a time dependent manner too. The mRNA expression levels of leptin in the 4 hypoxia groups were 0.144+/-0.009, 0.336+/-0.017, 0.524+/-0.013, and 0.671+/-0.021 respectively, increasing in a time dependent manner, however, there was no significant differences in the mRNA expression levels of HIF-1alpha among the groups exposed to hypoxia for different courses of time (all P>0.05). The protein expression levels of HIF-1alpha and leptin, and the mRNA expression levels of leptin in the groups exposed to hypoxia for different courses of time were all significantly higher than those of the control (0 h hypoxia) group (all P<0.01). The mRNA and protein expression levels of leptin in the A549 cells exposed to GL331 and hypoxia were decreased dose-dependently. CONCLUSION: The expression of leptin is up-regulated by hypoxia and regulated by HIF-1alpha.