Revealing the oncogenic role of elevated GNL3L expression in esophageal squamous cell carcinoma: insights into the STAT3 pathway.

Background: Esophageal squamous cell carcinoma (ESCC) patients carries a poor prognosis, with limited effective therapeutic targets. This study aimed to clarify the clinical significance of guanine nucleotide-binding protein like 3-like (GNL3L) protein expression in ESCC and its role in malignant progression. Methods: GNL3L expression and associated cancer-promoting pathways in ESCC were interrogated via bioinformatics analysis through use of The Cancer Genome Atlas (TCGA) database. Subsequent verification of GNL3L protein expression in ESCC, coupled with clinical data, was conducted through immunohistochemistry and followed by a comprehensive prognostic analysis. We further investigated potential signaling pathways facilitating ESCC progression, employing a combination of bioinformatics analysis and immunohistochemical (IHC) experiments. Results: Bioinformatics analysis unveiled a significant elevation in GNL3L expression, particularly in gastrointestinal tumors and ESCC. Immunohistochemistry confirmed elevated GNL3L expression in ESCC tissues. Regression analysis established a correlation between elevated GNL3L expression and advanced tumor node metastasis (TNM) stage, with high expression associated with poor prognosis in patients with ESCC. Our integrated approach of bioinformatics and IHC analysis indicated a potential role of the signal transducers and activators of transcription 3 (STAT3) signaling pathway in ESCC progression. Conclusions: High GNL3L expression significantly contributes to the malignant progression of ESCC. This study further elucidates the mechanisms driving ESCC progression and offers possible insights for more effective diagnosis and treatment strategies.

Association of leptin receptor polymorphisms with susceptibility of non-small cell lung cancer: Evidence from 2249 subjects.

Non-small cell lung cancer (NSCLC) is increasing dramatically. It is believed that energy metabolism-related genes could play an important role in etiology of NSCLC. In this study, we sought to assess the correlation between three LEPR single nucleotide polymorphisms (rs1137101, rs1137100 and rs6588147) with NSCLS susceptibility. In total, 1193 NSCLC cases and 1056 controls were included. SNPscan™ genotyping method was used to analyze the genotypes of LEPR polymorphisms. Compared to rs6588147 GG in LEPR gene, this study identified a protective role of LEPR rs6588147 GA and GA/AA for the occurrence of NSCLC (GA vs. GG [p = 0.021] and GA/AA vs. GG [p = 0.030]). As well, we found that a protective role of LEPR rs6588147 for the occurrence of non-SCC subgroup (p < 0.05). By logistic regression analysis, we found that the rs6588147 A allele related genotypes might play a protective role for the occurrence of NSCLC in drinking, BMI ≥24 kg/m2, smoking and male subgroups. We also found that the rs1137101 A allele related genotypes played a protective role for the occurrence of NSCLC in male, younger participants (under 59 years) and overweight/obesity (BMI ≥24 kg/m2) subgroups. We found that LEPR Ars1037100Ars1037101Ars6588147 haplotype might play a protective role for the occurrence of NSCLC (p = 0.013). In addition, our findings indicated that LEPR rs1137100 G>A SNP might increase the risk of lymph node metastases (p = 0.038). This study highlights that LEPR rs6588147, rs1137101 genotypes and LEPR Ars1037100Ars1037101Ars6588147 haplotype are correlated with the occurrence of NSCLC. LEPR rs1137100 G>A SNP increases the risk of lymph node metastases.

Prognostic value of inflammatory nutritional scores in locally advanced esophageal squamous cell carcinoma patients undergoing neoadjuvant chemoimmunotherapy: a multicenter study in China.

Objective: This study investigates the prognostic significance of inflammatory nutritional scores in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy. Methods: A total of 190 LA-ESCC patients were recruited from three medical centers across China. Pre-treatment laboratory tests were utilized to calculate inflammatory nutritional scores. LASSO regression and multivariate logistic regression analyses were conducted to pinpoint predictors of pathological response. Kaplan-Meier and Cox regression analyses were employed to assess disease-free survival (DFS) prognostic factors. Results: The cohort comprised 154 males (81.05%) and 36 females (18.95%), with a median age of 61.4 years. Pathological complete response (pCR) was achieved in 17.38% of patients, while 44.78% attained major pathological response (MPR). LASSO and multivariate logistic regression analyses identified that hemoglobin, albumin, lymphocyte, and platelet (HALP) (P=0.02) as an independent predictors of MPR in LA-ESCC patients receiving neoadjuvant chemoimmunotherapy. Kaplan-Meier and log-rank tests indicated that patients with low HALP, MPR, ypT1-2, ypN0 and, ypTNM I stages had prolonged DFS (P < 0.05). Furthermore, univariate and multivariate Cox regression analyses underscored HALP (P = 0.019) and ypT (P = 0.029) as independent predictive factors for DFS in ESCC. Conclusion: Our study suggests that LA-ESCC patients with lower pre-treatment HALP scores exhibit improved pathological response and reduced recurrence rate. As a comprehensive index of inflammatory nutritional status, pre-treatment HALP may be a reliable prognostic marker in ESCC patients undergoing neoadjuvant chemoimmunotherapy.

LncRNA PRKCA-AS1 promotes LUAD progression and function as a ceRNA to regulate S100A16 by sponging miR-508-5p.

Objective: This study aimed to elucidate the underlying mechanism of LncRNA PRKCA-AS1 in lung adenocarcinoma (LUAD). Methods: The expression of LncRNA PRKCA-AS1, miR-508-5p and S100A16, in LUAD tissues or cell lines (NCI-H520 and H1299) was analyzed with qRT-PCR. The clinical diagnostic value of LncRNA PRKCAAS1, miR-508-5p and S100A16 in LUAD were analyzed by receptor operating characteristic (ROC) curve. Then we knockdown or overexpression of PRKCAAS1 in NCI-H520 and H1299 cells, and the cell function test was applied to detect the activity and metastasis level of cells in different transfection groups. Then Pearson correlation analysis was used for the correlation between miR-508-5p and PRKCA-AS1. The dual-luciferase reporter experiment and CHIRP analysis was conducted to verify the target binding relationship of PRKCA-AS1, miR-508-5p or S100A16. FISH assay analyzed the colocalization of PRKCA-AS1 and miR-508-5p in NCI-H520 and H1299 cells. Rescue experiment and tumorigenesis experiment in nude mice further explore the regulatory mechanisms of LncRNA PRKCA-AS1, miR-508-5p and S100A16 on LUAD progression in vitro and in vivo. Results: From the results, PRKCA-AS1 and S100A16 were up-regulated in LUAD tissues, while miR-508-5p was downregulated compared with the adjacent tissues. And gain-of-function revealed that PRKCA-AS1 knock-down apparently suppressed the cell proliferation and metastasis, whereas miR-508-5p inhibitors or S100A16 overexpression showed a opposite effect. In addition, there is evidence that PRKCA-AS1, miR-508-5p and S100A16 have a targeted regulatory relationship. Moreover, rescue experiment and tumorigenesis experiment in nude mice further confirmed that LncRNA PRKCA-AS1 regulates S100A16 through sponging miR-508-5p to regulate LUAD progression in vitro and in vivo. Conclusion: These results demonstrated that LncRNA PRKCA-AS1 might regulate LUAD by acting as a ceRNA via sponging miR-508-5p and regulating S100A16 expression, indicating that manipulation of PRKCA-AS1 might be a potential therapeutic strategy in LUAD.

Therapeutic Potential of a Novel Lytic Phage, vB_EclM_ECLFM1, against Carbapenem-Resistant Enterobacter cloacae.

The global rise of multidrug-resistant Enterobacter cloacae strains, especially those that are resistant to carbapenems and produce metallo-ß-lactamases, poses a critical challenge in clinical settings owing to limited treatment options. While bacteriophages show promise in treating these infections, their use is hindered by scarce resources and insufficient genomic data. In this study, we isolated ECLFM1, a novel E. cloacae phage, from sewage water using a carbapenem-resistant clinical strain as the host. ECLFM1 exhibited rapid adsorption and a 15-min latent period, with a burst size of approximately 75 PFU/infected cell. Its genome, spanning 172,036 bp, was characterized and identified as a member of Karamvirus. In therapeutic applications, owing to a high multiplicity of infection, ECLFM1 showed increased survival in zebrafish infected with E. cloacae. This study highlights ECLFM1's potential as a candidate for controlling clinical E. cloacae infections, which would help address challenges in treating multidrug-resistant strains and contribute to the development of alternative treatments.

Dynamic Analysis of the Impact of Micropapillary Component on Different Recurrence Patterns of Pathological Stage IA3 Lung Adenocarcinoma: A Multicenter, Retrospective Study.

BACKGROUND: This study aimed to evaluate the dynamic impact of the micropapillary (MIP) component on local recurrence (LR), distant metastasis (DM), and multiple recurrence (MR) of pathological stage IA3 lung adenocarcinoma. METHODS: Between July 2012 and July 2020, a total of 351 patients at two medical institutions were enrolled in this study. Cumulative incidence of curves, dynamic risk curves, and time-dependent multivariate analysis was performed to evaluate the effect of the MIP component on patients. RESULTS: The 5-year cumulative incidence of total recurrence with or without an MIP component was 34.2% and 12.3%, respectively (p = 0.001). In three recurrence patterns, our findings revealed that the 5-year cumulative incidence of LR (p = 0.048) and DM (p = 0.005) was higher in the 'MIP-present' group than in the 'MIP-absent' group. In the dynamic recurrence curve, the risk of the three recurrence patterns was different and varied over time between the two groups, especially in DM. Moreover, the dynamic cumulative event curve showed that after 1, 2, and 3 years of survival, the cumulative incidence of DM in the group with MIP continued to be higher than that in the group without MIP (all p < 0.05). Time-dependent Cox regression analysis indicated that the MIP component continued to be an independent risk factor for the cumulative incidence of DM in patients with 3-year survival. CONCLUSIONS: Of the three recurrence patterns, the MIP component mainly aggravated the risk of DM in patients with pathological stage IA3 lung adenocarcinoma, which persisted for 3 years.

Safety and economic analysis of the EasyEndo disposable endoscopic cutting and stapling device for VATS lobectomy or segmentectomy in lung cancer patients: a retrospective study.

Objective: The aim of this retrospective study was to investigate the safety and economic aspects of using the EasyEndo disposable endoscopic cutting and stapling device for video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy in patients with lung cancer. The choice between the two staplers was influenced by changes in our hospital's procurement policy; Johnson EC45A was used before January 2022 and was then replaced by the EasyEndo stapler. Methods: We reviewed and analyzed consecutive patients with lung cancer who underwent VATS segmentectomy from March 2021 to December 2022. Inclusion criteria included patients with suspected non-small cell lung cancer (NSCLC) who were eligible for surgical resection. The surgical procedures were performed using either the EasyEndo or Johnson EC45A staplers. Intraoperative variables, postoperative outcomes, and cost analysis were compared between the two groups. Results: A total of 1556 patients were included in the study, with 775 patients in the Control group and 781 patients in the EasyEndo group. There were no significant differences in patient characteristics between the two groups. Intraoperative variables, including blood loss, blood transfusion, and operation time, showed no significant differences between the groups. Postoperative outcomes, such as hospital stay, drainage tube placement time, and incidence of complications, were also comparable between the two groups. However, there was a significant difference in the cost of stapler usage, with the EasyEndo group showing a lower cost compared to the Control group. Conclusion: The EasyEndo disposable endoscopic cutting and stapling device demonstrated comparable safety and effectiveness to the Johnson EC45A stapler in VATS segmentectomy for lung cancer patients. Moreover, the use of the EasyEndo stapler resulted in cost savings, indicating its potential economic benefits for healthcare institutions.

Impact of minimally invasive total mesoesophageal excision and minimally invasive esophagectomy on failure patterns of locally advanced esophageal squamous cell carcinoma: a matched cohort study with long-term follow-up.

BACKGROUND: The effects of minimally invasive total mesoesophageal excision (MITME) on the long-term prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this study was to compare the static and dynamic failure patterns of MITME and minimally invasive esophagectomy (MIE) for locally advanced ESCC. METHODS: We use propensity score matching (PSM) method to analyze the postoperative failure patterns of the two groups. Cumulative event curves were analyzed for cumulative incidence of failure between different groups, and independent prognostic factors were assessed using time-dependent multivariate analyses. The risk of dynamic failure calculated at 12-month intervals was compared between the two groups using the lifetime table. RESULTS: A total of 366 ESCC patients were studied by 1:1 PSM for T stage and TNM stage (MITME group, n = 183; MIE group, n = 183). In the matched cohort, there was significant differences between the MITME and MIE groups in the failure pattern of regional lymph node recurrence (0.5 vs 3.8%, P = 0.032) and non-tumor death (10.9 vs 31.7%, P < 0.001). The cumulative event curve found that the 5-year cumulative failure rate was lower in the MITME group than in the MIE group (3.3 vs 17.1%, P = 0.026) after 5 years of survival. In addition, multivariate Cox regression analysis showed that MIE was an independent poor prognostic factor for a high cumulative failure rate in locally advanced ESCC patients at 5 years after surgery (HR:4.110; 95% CI 1.047-16.135; P = 0.043). The dynamic risk curve showed that the MITME group had a lower risk of failure within 5 years after surgery than the MIE group. CONCLUSION: Considering that MITME can significantly improve the postoperative failure pattern and the benefit lasts for at least 5 years, it is feasible to use MITME as a treatment for locally advanced ESCC.

Reshaping immunometabolism in the tumour microenvironment to improve cancer immunotherapy.

The evolving understanding of cellular metabolism has revealed a the promise of strategies aiming to modulate anticancer immunity by targeting metabolism. The combination of metabolic inhibitors with immune checkpoint blockade (ICB), chemotherapy and radiotherapy may offer new approaches to cancer treatment. However, it remains unclear how these strategies can be better utilized despite the complex tumour microenvironment (TME). Oncogene-driven metabolic changes in tumour cells can affect the TME, limiting the immune response and creating many barriers to cancer immunotherapy. These changes also reveal opportunities to reshape the TME to restore immunity by targeting metabolic pathways. Further exploration is required to determine how to make better use of these mechanistic targets. Here, we review the mechanisms by which tumour cells reshape the TME and cause immune cells to transition into an abnormal state by secreting multiple factors, with the ultimate goal of proposing targets and optimizing the use of metabolic inhibitors. Deepening our understanding of changes in metabolism and immune function in the TME will help advance this promising field and enhance immunotherapy.

Additional neoadjuvant immunotherapy does not increase the risk of anastomotic leakage after esophagectomy for esophageal squamous cell carcinoma: a multicenter retrospective cohort study.

PURPOSE: Neoadjuvant chemoimmunotherapy (nICT) is a novel and promising therapy model for locally advanced esophageal squamous cell carcinoma.The objective of this study aimed to assessed the impact of additional neoadjuvant immunotherapy on patients' short-term outcomes, particularly the incidence of anastomotic leakage (AL) and pathological response. METHODS: Patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (nCT)/ nICT combination with radical esophagectomy were enrolled from three medical centers in China. The authors used propensity score matching (PSM, ration:1:1, caliper=0.01) and inverse probability processing weighting (IPTW) to balance the baseline characteristics and compare the outcomes. Conditional logistic regression and weighted logistic regression analysis were used to further evaluate whether additional neoadjuvant immunotherapy would increase the risk of postoperative AL. RESULTS: A total of 331 patients getting partially advanced ESCC receiving nCT or nICT were enrolled from three medical centers in China. After PSM/IPTW, the baseline characteristics reached an equilibrium between the two groups. After matching, there were no significant difference in the AL incidence between the two groups ( P =0.68, after PSM; P =0.97 after IPTW), and the incidence of AL in the two groups was 15.85 versus 18.29%, and 14.79 versus 15.01%, respectively. After PSM/IPTW, both groups were similar in pleural effusion and pneumonia. After IPTW, the nICT group had a higher incidence of bleeding (3.36 vs. 0.30%, P =0.01), chylothorax (5.79 0.30%, P =0.001), and cardiac events (19.53 vs. 9.20%, P =0.04). recurrent laryngeal nerve palsy (7.85 vs. 0.54%, P =0.003). After PSM, both groups were similar in palsy of the recurrent laryngeal nerve (1.22 vs. 3.66%, P =0.31) and cardiac events (19.51 vs. 14.63%, P =0.41). Weighted logistic regression analysis showed that additional neoadjuvant immunotherapy was not responsible for AL (OR=0.56, 95% CI: [0.17, 1.71], after PSM; 0.74, 95% CI: [0.34,1.56], after IPTW). The nICT group had dramatically higher pCR in primary tumor than the nCT group ( P =0.003, PSM; P =0.005, IPTW), 9.76 versus 28.05% and 7.72 versus 21.17%, respectively. CONCLUSIONS: Additional neoadjuvant immunotherapy could benefit pathological reactions without increasing the risk of AL and pulmonary complications. The authors require further randomized controlled research to validate whether additional neoadjuvant immunotherapy would make a difference in other complications, and determine whether pathologic benefits could translate into prognostic benefits, which would require longer follow-up.

Effects of a ground-glass opacity component on the recurrence and survival of pathological stage IA3 lung adenocarcinoma: a multi-institutional retrospective study.

Background: This study aimed to evaluate the effect of the presence of a radiographically manifested ground-glass opacity (GGO) component on the prognosis of patients with pathological stage IA3 lung adenocarcinoma. Methods: Patients diagnosed with pathological stage IA3 lung adenocarcinoma who underwent radical surgery at two medical institutions in China between July 2012 and July 2020 were enrolled. The cumulative incidence of recurrence (CIR) and cumulative incidence of death (CID) in patients with and without a GGO component were compared. Risk curves for the recurrence and tumor-related death overtime were analyzed between the two groups according to life table. In order to validate the prognostic value of GGO components, the recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated. Decision curve analysis (DCA) was performed to evaluate the clinical benefit rate of different models. Results: Among the 352 included patients, the presence of a GGO component was radiographically shown in 166 (47.2%) patients, while 186 (52.8%) displayed solid nodules. Patients exhibiting the absence of a GGO component had higher incidences of total recurrence (17.2% vs. 3.0%, P<0.001), local-regional recurrence (LRR) (5.4% vs. 0.6%, P=0.010), distant metastasis (DM) (8.1% vs. 1.8%, P=0.008), and multiple recurrences (4.3% vs. 0.6%, P=0.028) than the presence-GGO component group. The 5-year CIR and CID were 7.5% and 7.4% in the presence-GGO component group, and 24.5% and 17.0% in the absence-GGO component group, respectively, with statistically significant differences between the two groups (P<0.05). The risk of recurrence in patients with the presence of GGO components showed a single peak at 3 years postoperatively, while patients with the absence of GGO components showed a double peak at 1 and 5 years after surgery, respectively. However, the risk of tumor-related death peaked in both groups at 3 and 6 years postoperatively. Multivariate Cox analysis showed that the presence of a GGO component was a favorable independent risk factor for pathological stage IA3 lung adenocarcinoma patients (P<0.05). Conclusions: Pathological stage IA3 lung adenocarcinoma with or without GGO components are two types of tumors with different invasive abilities. In clinical practice, we should develop different treatment and follow-up strategies.

IL-1RA inhibits esophageal carcinogenesis and lymphangiogenesis via downregulating VEGF-C and MMP9.

Interleukin-1 receptor antagonist (IL-1RA) has been shown to play an important role in cancer progression. However, its pathogenic effects and molecular mechanism in the malignant progression of esophageal squamous cell carcinoma (ESCC) remain largely unknown. This study was designed to explore the function of IL-1RA in ESCC and determine the relationship between IL-1RA and lymph node metastasis in ESCC patients. The clinical relevance of IL-1RA in relation to the clinicopathological features and prognosis of 100 ESCC patients was analyzed. The function and underlying mechanisms of IL-1RA in the growth, invasion, and lymphatic metastasis in ESCC were explored both in vitro and in vivo. The therapeutic effect of anakinra, an IL-1 receptor antagonist, on ESCC was also evaluated in animal experiments. Downregulation of IL-1RA was observed in ESCC tissues and cells and was found to be strongly correlated with pathological stage (P = 0.034) and lymphatic metastasis (P = 0.038). Functional assays demonstrated that upregulation of IL-1RA reduced cell proliferation, migration, and lymphangiogenesis both in vitro and in vivo. Mechanistic studies revealed that overexpression of IL-1RA activated the epithelial-to-mesenchymal transition (EMT) in the ESCC cells through activation of MMP9 and regulation of the expression and secretion of VEGF-C through the PI3K/NF-κB pathway. Anakinra treatment resulted in significant inhibition of tumor growth, lymphangiogenesis, and metastasis. IL-1RA inhibits lymph node metastasis of ESCC by regulating the EMT through activation of matrix metalloproteinase 9(MMP9) and lymphangiogenesis, driven by VEGF-C and the NF-κB signaling pathway. Anakinra may be an effective drug for the inhibition of ESCC tumor formation and lymph node metastasis.

A Multi-institutional Analysis of the Combined Effect of Micropapillary Component and Consolidation-to-Tumor Ratio >0.5 on the Prognosis of Pathological, Stage IA3, Lung Adenocarcinoma.

INTRODUCTION: The study investigated the synergistic effect of the micropapillary (MIP) component and consolidation-to-tumor ratio (CTR) on the recurrence and survival of patients with pathologic stage IA3 lung adenocarcinoma. METHODS: We enrolled 419 patients confirmed pathological stage IA3 adenocarcinoma from four institutions. Kaplan-Meier analysis was performed to examine the value of the MIP component and CTR on relapse-free survival (RFS) and overall survival (OS). The cumulative recurrence between different stages was analyzed by using cumulative event curves. RESULTS: RFS (P < 0.0001) and OS (P = 0.008) in the presence of the MIP group were significantly lower than those in the absence of the MIP group, and CTR > 5 only reduced RFS (P = 0.0004), but not OS (P = 0.063), in the patients. In addition, the prognosis of patients with both the MIP component and CTR > 5 was worse than that of those without the MIP component or CTR ≤ 5. Therefore, we established new subtypes of the stage IA3: IA3a, IA3b, and IA3c. RFS and OS for IA3c staging were significantly lower than those for IA3a and IA3b. For IA3c, the cumulative incidence of local recurrence (P < 0.001) and that of distant metastasis (P = 0.004) were significantly higher than those for IA3a and IA3b. CONCLUSIONS: The MIP component combined with CTR > 0.5 can effectively predict the prognosis of patients with pathological stage IA3 lung adenocarcinoma and may offer more detailed recurrence and survival information according to the established subtype stage of IA3.

Inflammatory and Nutritional Status Influences Outcomes of Minimally Invasive Esophagectomy.

INTRODUCTION: The potential association between severe postoperative complications (SPC) and the oncological outcomes of esophageal squamous cell carcinoma (ESCC) patients according to the different Naples Prognostic Score (NPS) of the inflammatory nutritional status after minimally invasive esophagectomy (MIE) is unclear. METHODS: Kaplan-Meier survival analysis was used to evaluate overall survival (OS) and disease-free survival (DFS) between with or without SPC (Clavien-Dindo grade ≥ III) in low NPS status (NPS = 0 or 1) and high NPS status (NPS = 2 or 3 or 4) patients. Cox multivariable analysis was carried out to analyze the various independent factors of OS and DFS, and a nomogram based on SPC was established. RESULTS: A total of 20.7% (125/604) ESCC patients developed SPC after MIE. Patients with SPC exhibited poor 5-year OS and DFS compared to those without SPC (all P < 0.001). Further analysis revealed that SPC significantly reduced OS and DFS in patients with high NPS status (all P < 0.001) but had little effect on the prognosis of patients with low NPS status (all P > 0.05). Multivariable Cox analysis revealed that SPC could be an independent influence indicator for OS and DFS in patients with high NPS status. Therefore, a novel nomogram combining SPC and tumor-node-metastasis (TNM) staging has been developed, which was found to be relatively more accurate in predicting OS and DFS than TNM staging alone. CONCLUSION: Severe complications can adversely affect the long-term oncological outcome of ESCC patients with high systemic inflammatory response and malnutrition after MIE.

Identification of nine mutant genes and establishment of three prediction models of organ tropism metastases of non-small cell lung cancer.

BACKGROUND: Most Non-small cell lung cancer (NSCLC) patients tend to have metastases at the initial diagnosis. However, limited knowledge has been established regarding which factors, are associated with its metastases. This study aims to identify more biomarkers associated with its organ tropism metastasis and to establish models for prediction of its metastatic organs. METHODS: We performed targeted next-generation sequencing (NGS) to detect genes related to lung cancer in 272 patients with primary advanced NSCLC from Northeast China. We adopted Fisher test, multivariate logistic regression analysis to identify metastasis-related gene mutations and to establish prediction models. RESULTS: Mutations of EGFR (p = 0.0003, OR = 2.554) (especially EGFR L858R [p = 0.02, OR = 2.009]), ATM (p = 0.008, OR = 11.032), and JAK2 (p = 0.009, OR = Inf) were positively and of TP53 exon4mut (p = 0.001, OR = 0.173) was negatively correlated with lung metastasis, and those of CSF1R (p = 0.01, OR = Inf), KIT (p = 0.03, OR = 4.746), MYC (p = 0.05, OR = 7.938), and ERBB2 (p = 0.02, OR = 2.666) were positively correlated with pleural dissemination; those of TP53 (p = 0.01, OR = 0.417) was negatively, while of SMAD4 (p = 0.03, OR = 4.957) was positively correlated with brain metastasis of NSCLC. Additionally, smoking history (p = 0.004, OR = 0.004) was negatively correlated with pleural dissemination of NSCLC. Furthermore, models for prediction of lung metastasis (AUC = 0.706), pleural dissemination (AUC = 0.651), and brane metastasis (AUC = 0.629) were established. CONCLUSION: Taken together, this study revealed nine mutant genes and smoking history associated with organ tropism metastases of NSCLC and provided three models for the prediction of metastatic organs. This study enables us to predict the organs to which non-small cell lung cancer metastasizes before it does develop.

External validation of a risk model for survival prediction in older patients with cancer undergoing elective abdominal surgery: a prospective cohort study.

We previously developed a Chang Gung Memorial Hospital (CGMH) model to predict the 1-year postoperative mortality risk in patients with solid cancer undergoing cancer surgery. This study aimed to externally validate the CGMH score for survival outcome and surgical complication prediction in a prospective patient cohort. A total of 345 consecutive patients aged ≥65 years who underwent elective abdominal surgery for cancer treatment were prospectively enrolled. Patients were categorized into the low, intermediate, high, and very high-risk groups according to the CGMH score for comparison. The postoperative 1-year mortality rate was 12.5% in the entire cohort. The postoperative 1-year mortality rates were 0%, 2.2%, 14.0%, and 31.6% among patients in the low, intermediate, high, and very-high risk groups, respectively. The c-statistic of the CGMH model was 0.82 (95% confidence interval [CI], 0.76-0.88) for predicting the 1-year mortality risk. Hazard ratios for overall survival were 3.73 (95% CI, 2.11-6.57; P<0.001) and 10.1 (95% CI, 5.84-17.6; P<0.001) when comparing the high and very-high risk groups with the low/intermediate risk groups, respectively. Patients in the higher CGMH risk groups had higher risks of adverse surgical outcomes in terms of longer length of hospital stay, major surgical complications, postoperative intensive care unit stay, and in-hospital death. The CGMH model accurately predicted thesurvival probabilityand risk of adverse surgical outcomes in older patients with cancer undergoing elective abdominal surgery. Our study justifies the prospective use of the CGMH model for survival outcome and safety profile predictionfor cancer surgery in older patients.

Establishment and validation of a nomogram model for predicting postoperative recurrence-free survival in stage IA3 lung adenocarcinoma: a retrospective cohort study.

Background: The increased use of computed tomography has brought a corresponding increase in the numbers of early-stage lung cancer patients receiving treatment. However, even for stage IA3 lung adenocarcinoma, many patients experience postoperative recurrence and metastasis. The existing TNM staging system for lung cancer does not take many clinical and pathological factors into consideration, resulting in the failure to detect and intervene as soon as possible in those with high recurrence risk. The purpose of this study was to explore the risk factors for postoperative recurrence-free survival (RFS) in patients with stage IA3 lung adenocarcinoma, and to construct and verify a nomogram model for predicting RFS in patients with the disease. Methods: This study analyzed patients with stage IA3 lung adenocarcinoma who underwent surgical treatment. Univariate and multivariate analysis were used to analyze the independent risk factors for postoperative RFS and establish a nomogram model. Concordance index (C-index), receiver operating characteristic curve, clinical decision analysis, and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. Data from two other institutions were used for external validation, and the nomogram scores were combined with X-tile software to screen high-risk groups of recurrence. Results: The internal cohort included 235 eligible patients with stage IA3 lung adenocarcinoma from 7,235 lung cancer. Multivariate analysis showed smoking, solid nodules, mucinous lung adenocarcinoma, and micropapillary component ≥5% were independent risk factors for RFS. A nomogram model was constructed based on the above results and the bootstrap method was used for internal validation. The internal and external validation C-indexes of the nomogram were 0.822 (95% CI: 0.751-0.891) and 0.812, respectively, indicating the obvious prediction performance was good. The X-tile software combined with nomogram scores showed the low-risk group (5-RFS rate, 0.65-0.99) had better RFS than the high-risk group (5-RFS rate, 0.20-0.65) (P<0.0001). Conclusions: We constructed a nomogram model for predicting postoperative RFS in patients with stage IA3 lung adenocarcinoma which can individually evaluate the risk of postoperative recurrence, screen high-risk groups, and develop individualized follow-up and intervention strategies to improve the survival rate of the patients.