Predictive nomogram for bone metastases in lung cancer based on monocyte infiltration.

The presence of bone metastases (BM) in patients with lung cancer is indicative of a worse prognosis. The present study aims to investigate the risk factors associated with BM in patients with lung cancer. Patients with lung cancer admitted to the First Affiliated Hospital of Anhui Medical University between June 2019 and September 2021 were enrolled in this study. A nomogram was constructed based on the outcomes derived from univariate and multivariate analyses. Concordance index, calibration plots, receiver operating characteristic curves, and decision curve analysis were used to evaluate the nomogram. To substantiate the influence of monocytes on lung cancer BM, various assays, including cell co-culture, Transwell, wound-healing assays, and immunohistochemistry and immunofluorescence staining, were conducted. Statistical analyses were performed using SPSS 22.0 software and GraphPad Prism 7.0. A total of 462 eligible patients were enrolled, comprising 220 with BM and 242 without. Multivariate analysis revealed that histological type, medical history, monocyte percentage, and LDH (Lactate Dehydrogenase) and ALP (Alkaline Phosphatase) levels were independent risk factors for BM in lung cancer. Transwell and wound-healing assays indicated that co-culture with monocytes significantly enhanced the migration and invasion capabilities of A549 cells in vitro. Immunohistochemistry and immunofluorescence analyses demonstrated a noteworthy increase in monocyte infiltration in the primary lesions of patients with lung cancer with BM. In conclusion, this study successfully constructed and validated a precise, straightforward, and cost-effective prognostic nomogram for patients with lung cancer with BM.

Clinical Pathological Characteristics and Prognosis of Multigene Co-Mutations in Elderly Patients With Non-Small Cell Lung Cancer: A Retrospective Analysis.

Background: With the development and wide application of next-generation sequencing (NGS), multiple-gene mutations related to lung cancer are detected using this technology. Notably, even multigene concomitant mutations (co-mutations), which occur at a relatively low incidence, can be detected more effectively using NGS. It is well-known that the percentages of non-small cell lung cancer (NSCLC) in the elderly lung cancer population are also gradually increasing, while its prognosis is hard and the quality of long-term survival is poor. This study aimed at investigating the common clinicopathologic features of multigene co-mutations for better evaluating the prognosis of elderly NSCLC patients. Methods: A total of 464 NSCLC patients were divided into 3 groups according to the types of gene mutation, whose clinical data were retrospectively analyzed. Results: In total, 38.36% (178/464) of NSCLC patients were in the nonmutation group, 50% in the single-gene mutation group, and 11.64% in the multigene co-mutation group. Nonmutation, single-gene mutation, and co-mutation groups were all prone to occur in male adenocarcinoma patients (P < .05). EGFR gene mutation rates were the highest in the single-gene mutation and co-mutation groups (54.31% and 24.35%). In the co-mutation group, the incidence of EGFR/PIK3CA, LK/KRAS, and EGFR/MET co-mutations was the highest (16.67%, 11.11%, and 7.41%). ALK/HER2/MET, EGFR/HER2/MET, and EGFR/HER2/MET/ROS1 multiple-gene co-mutations were, respectively, found in 1 case, and the multigene co-mutation patients commonly had a worse median progression-free survival (PFS) than that of single-gene mutation (7.13 vs 12.34 months, P = .013). Conclusion: With the application of NGS, the detectable rates of gene co-mutation are increasingly high in elderly patients with NSCLC, which mainly occurs in male adenocarcinoma patients commonly with poor PFS. It will be critically necessary to conduct multigene detections by NGS for directing targeted therapy of elderly NSCLC patients.

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.

Concomitant genetic alterations are associated with plasma D-dimer level in patients with non-small-cell lung cancer.

Objective: D-dimer is correlated to the poor prognosis of non-small-cell lung cancer. The study aimed to investigate the association between plasma D-dimer and concomitant mutations in non-small-cell lung cancer. Methods: A total of 517 non-small-cell lung cancer patients were recruited and tested for ALK, BRAF, EGFR, HER2/ERBB2, KRAS, MET, PIK3CA, RET and ROS1 mutation by next-generation sequencing. Multiple gene mutation information, clinical baseline data and laboratory test data were analyzed statistically. Results: All patients were divided into three groups: wild-type group, single-gene mutation group and concomitant mutation group. The analysis of D-dimer, uric acid, gender, family history, smoking history, histology and distant metastasis all showed significant differences in the three groups (p < 0.05). D-dimer was considered as a risk factor for concomitant mutations according to the unordered multiple logistic regression analysis. The receiver operating characteristic curve analysis indicated that D-dimer had an important predictive value for the occurrence of concomitant mutations (area under the curve [AUC]: 0.94; sensitivity: 88.71%; specificity: 86.46). There was significantly shorter median progression-free survival in the concomitant mutation group compared with the single mutation group (7.70 months vs 14.00 months; p = 0.0133). Conclusion: Plasma D-dimer is significantly associated with concomitant mutations and may be regarded as a potent predictor of concomitant mutations for non-small-cell lung cancer patients.

Plain language summary Non-small-cell lung cancer (NSCLC) is a common type of lung cancer. Gene mutation is an important cause of NSCLC. The authors are eager to predict the occurrence of gene mutations through some non-specific indicators. These non-specific indicators need to meet the conditions of simple acquisition and low detection cost. In this study, patients are divided into wild-type, single-gene mutation and concomitant mutation groups based on next-generation sequencing results. The authors have observed that the levels of D-dimer are significantly increased in some NSCLC patients. And D-dimer is considered to be a risk factor for concomitant mutations and had important predictive value for concomitant mutations. This study provides a new predictive and prognostic indicator (D-dimer) for patients with concomitant mutations. D-dimer is a new method for predicting concomitant mutations and guides further treatment in NSCLC.

Functional roles of E3 ubiquitin ligases in gastric cancer.

To date, >650 E3 ubiquitin ligases have been described in humans, including >600 really interesting new genes (RINGs), 28 homologous to E6-associated protein C-terminus (HECTs) and several RING-in-between-RINGs. They are considered key regulators and therapeutic targets of many types of human cancers, including gastric cancer (GC). Among them, some RING and HECT E3 ligases are closely related to the proliferation, infiltration and prognosis of GC. During the past few years, abnormal expressions and functions of many E3 ligases have been identified in GC. However, the functional roles of E3 ligases in GC have not been fully elucidated. The present article focuses on the functional roles of E3 ligases related to the proteasome in GC. In this comprehensive review, the latest research progress on E3 ligases involved in GC and elaborate their structure, classification, functional roles and therapeutic value in GC was summarized. Finally, 30 E3 ligases that serve essential roles in regulating the development of GC were described. Some of these ligases may serve as oncogenes or tumor suppressors in GC, whereas the pathological mechanism of others needs further study; for example, constitutive photomorphogenic 1. In conclusion, the present review demonstrated that E3 ligases are crucial tumor regulatory factors and potential therapeutic targets in GC. Therefore, more studies should focus on the therapeutic targeting of E3 ligases in GC.

The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review.

BACKGROUND: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. DATA SOURCES: Relevant research articles published before 1st March 2018 in PubMed, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios (HRs) [95% confidence intervals (CI)] and forest plots. RESULTS: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival (OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone (HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group (HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group (HR = 0.60; P < 0.001), R1 resection group (HR = 0.71; P = 0.04), LN-positive diagnosis group (HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group (HR = 0.42; P < 0.001), distal cholangiocarcinoma group (HR = 0.48; P = 0.17), R0 resection group (HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group (HR = 0.90; P = 0.66), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.

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.