Single-cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation.

BACKGROUND: Aberrant activation of the phosphatidlinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway has been shown to play an important role in lung adenocarcinoma (LUAD). The effect of KRAS mutations, one of the important signatures of LUAD, on the PI3K/AKT/mTOR pathway in LUAD remains unclear. METHODS: The Seurat package and principal component analysis were used for cell categorization of single-cell RNA sequencing data of LUAD. The AUCell score was used to assess the activity of the PI3K/AKT/mTOR pathway. Meanwhile, using the gene expression profiles and mutation profiles in the The Cancer Genome Atlas dataset, LUAD patients were categorized into KRAS-mutant (KRAS-MT) and KRAS-wild-types (KRAS-WT), and the corresponding enrichment scores were calculated using gene set enrichment analysis analysis. Finally, the subpopulation of cells with the highest pathway activity was identified, the copy number variation profile of this subpopulation was inscribed using the inferCNV package and the CMap database was utilized to make predictions for drugs targeting this subpopulation. RESULTS: There is higher PI3K/AKT/mTOR pathway activity in LUAD epithelial cells with KRAS mutations, and high expression of KRAS, PIK3CA, AKT1 and PDPK1. In particular, we found significantly higher levels of pathway activity and associated gene expression in KRAS-MT than in KRAS-WT. We identified the highest pathway activity on a subpopulation of GRB2+ epithelial cells and the presence of amplified genes within its pathway. Finally, drugs were able to target GRB2+ epithelial cell subpopulations, such as wortmannin, palbociclib and angiogenesis inhibitor. CONCLUSIONS: The present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.

Diagnosis and treatment of high-risk bilateral lung ground-glass opacity nodules.

In recent years, there has been a significant increase in the detection rate of Ground Glass Opacity (GGO) nodules through high-resolution computed tomography (HRCT). GGO is an imaging finding that encompasses various pathological types, some of which exhibit indolent growth, while others may represent early lung cancer or remain relatively stable, not significantly impacting the surgical treatment outcome. In clinical practice, patients often experience psychological anxiety when multiple pulmonary GGO nodules are present, and they may request simultaneous resection. However, there is currently no standardized criterion for determining when multiple GGO nodules should be resected. As personalized medicine continues to advance, the treatment approach for multiple pulmonary GGO nodules needs to prioritize accuracy. High-risk factors associated with multiple pulmonary GGO nodules may necessitate surgical intervention along with mediastinal lymph node dissection or sampling. This article provides a review of the characteristics, treatment methods, and clinical experiences related to multiple pulmonary GGO nodules, offering practical insights and guidance for healthcare professionals.

Analyzing robotic surgery impact on recovery quality & emotions.

Background: The objective of this study is to investigate the postoperative recovery quality and emotional status of patients with non-small cell lung cancer (NSCLC) who underwent robot-assisted and video-assisted thoracoscopic surgery using the 15-item Quality of Recovery (QoR-15) scale and to analyze the correlation. Methods: We collected clinical data from 320 patients with NSCLC who underwent lobectomy using either robot-assisted thoracoscopic surgery (RATS) or video-assisted thoracoscopic surgery (VATS) at our center from January 2021 to December 2022. We compared perioperative parameters and followed up after the operation using the QoR-15 scale to objectively assess the quality of postoperative recovery and physical and emotional status. Results: Apart from a notable distinction in anesthesia time, no significant differences were observed in other general data. Notably, the overall recovery rate for patients in the RATS group surpassed that of the VATS group (P < 0.05). Specifically, the recovery rates in the RATS group were significantly superior to those in the VATS group across nociceptive factors, emotional factors, activities of daily living, physiological factors, and cognitive ability (P < 0.05). Spearman correlation analysis between surgical methods and various indicators of the QoR-15 scale showed significant correlations between surgical methods (P < 0.05). Conclusion: The QoR-15 scale is a valuable tool for assessing the postoperative recovery quality in lung cancer patients. The RATS plays a significant role in promoting the swift postoperative recovery of patients and demonstrates excellent efficacy, safety, and reliability.

Diagnostic value of peripheral blood eosinophils for benign and malignant pulmonary nodule.

This retrospective study aims to assess the diagnostic utility of peripheral blood eosinophil counts in distinguishing between benign and malignant pulmonary nodules (PNs) prior to surgical intervention. We involved patients presenting with PNs measuring ≤30 mm as the primary CT imaging finding prior to surgical procedures at the General Hospital of Northern Theater Command in Shenyang, China, during the period spanning 2021 to 2022. Multivariable logistic regression analysis and receiver operator characteristic curve analysis, along with area under the curve (AUC) calculations, were used to determine the diagnostic value of eosinophil. A total of 361 patients with PN were included, consisting of 135 with benign PN and 226 with malignant PN. Multivariable logistic regression analysis showed that eosinophil percentage (OR = 1.909, 95% CI: 1.323-2.844, P < .001), absolute eosinophil value (OR = 0.001, 95% CI: 0.000-0.452, P = .033), tumor diameter (OR = 0.918, 95% CI: 0.877-0.959, P < .001), nodule type (OR = 0.227, 95% CI: 0.125-0.400, P < .001), sex (OR = 2.577, 95% CI: 1.554-4.329, P < .001), and age (OR = 0.967, 95% CI: 0.945-0.989, P = .004) were independently associated with malignant PN. The diagnostic value of regression model (AUC [95% CI]: 0.775 [0.725-0.825]; sensitivity: 74.3%; specificity: 71.1%) was superior to eosinophil percentage (AUC [95% CI]: 0.616 [0.556-0.677]; specificity: 66.8%; specificity: 51.1%) (Delong test: P < .001). Peripheral blood eosinophil percentage might be useful for early malignant PN diagnosis, and combining that with other characteristics might improve the diagnostic performance.

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway.

Background: The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17. Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p - an miRNA that could target ADAM10 - was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo. Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models. Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti- tumor drugs.

[Survival Analysis of Stage I Non-small Cell Lung Cancer Patients Treated with 
Da Vinci Robot-assisted Thoracic Surgery].

BACKGROUND: Da Vinci robotic surgery system is widely used in department of thoracic surgery. The aim of this study is to investigate the treatment outcome of stage I non-small cell lung cancer (NSCLC) via da Vinci Surgical System. METHODS: Clinical date of 347 stage I NSCLC patients, who underwent lobectomy and systematic node dissection from Jan. 2012 to Dec. 2017, were reviewed. 134 patients underwent robot-assisted thoracic surgery (RATS) and 213 patients underwent video-assisted thoracic surgery (VATS). To compare perioperative outcome (blood lose, postoperative drainage, drainage time, postoperative hospital stay, number of the LN dissection) and analyze overall survival (OS), disease free survival (DFS) of the two groups and prognostic factors. RESULTS: The RATS group got less blood lose [(49±39 mL for RATS vs (202±239) mL for VATS, P<0.05] and postoperative drainage [Day 1: (248±123) mL for RATS vs (350±213) mL for VATS; Day 2: (288±189) mL for RATS vs (338±189) mL for VATS, P<0.05]. There were no significant difference for drainage time (10±5 for RATS vs 11±8 for VATS, P<0.05) and postoperative hospital stay (13±6 for RATS vs 14±9 for VATS, P<0.05) between the two groups. The RATS group harvested a more number of mean stations (5±2 for RATS vs 4±2 for VATS) and amounts (18±9 for RATS vs 11±8 for VATS) of the lymph nodes, P<0.05. There was no statistically significant difference of OS between RATS and VATS group [1-year OS: 97.3% vs 96%; 3-year OS: 89.8% vs 83.1%; 5-year OS: 87.5 % vs 70.3%; overall survival time (mean): 61 months vs 59 months, P>0.05]; corresponding there had a statistically significant difference of DFS between the two groups [1-year DFS: 93.7% vs 91.3%; 3-year DFS: 87.7% vs 68.4%; 5-year DFS: 87.7% vs 52.5%; disease free survival time (mean): 61 months vs 50 months, P<0.05]. The univariate analysis found that the amounts of the lymph nodes dissection was the prognostic factor for OS and tumor diameter, surgical approach, stations and amounts of the lymph nodes dissection were respectively the prognostic factors for DFS. However, multivariate analysis found that there was not independently factors for OS, but the tumor diameter and surgical approach were independently associated with DFS. CONCLUSIONS: There was no significant difference about OS between the two groups, but the RATS got better DFS. RATS got more number of the LN dissection and less blood lose.

[A Paired Case Controlled Study Comparing the Short-term Outcomes of Da Vinci RATS and VATS Approach for Non-small Cell Lung Cancer].

BACKGROUND: Da Vinci Surgical System is one of the greatest inventions of the 20th century, which represents the development direction of the precise minimally invasive surgical techniques, the aim of this study was to comparing the short-term outcomes between da Vinci robot-assisted lobectomy and video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer. METHODS: 45 pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same period from January 2014 to January 2017. The operative time, estimated blood loss (EBL), total number and total groups of dissected lymph nodes, postoperative duration of drainage, the first day volume of drainage, total volume of drainage were compared. RESULTS: No perioperative death and convertion to thoracotomy occured in both groups. There were significant difference between RATS group and VATS group in EBL [(50.30±32.33) mL vs (208.60±132.63) mL], the first day volume of drainage [(275.00±145.42) mL vs (347.60±125.80) mL], the dissected total number [(22.67±9.67) vs (15.51±5.41)] and total team [(6.31±1.43) vs (4.91±1.04)] of lymph node. There were no significant difference in other outcomes. CONCLUSIONS: RATS is safe and effective and took better short-outcomes than VATS in non-small cell lung cancer.

[A comparative study of Da Vinci robot system with video-assisted thoracoscopy in the surgical treatment of mediastinal lesions].

BACKGROUND: In recent years, Da Vinci robot system applied in the treatment of intrathoracic surgery mediastinal diseases become more mature. The aim of this study is to summarize the clinical data about mediastinal lesions of General Hospital of Shenyang Military Region in the past 4 years, then to analyze the treatment effect and promising applications of da Vinci robot system in the surgical treatment of mediastinal lesions. METHODS: 203 cases of mediastinal lesions were collected from General Hospital of Shenyang Military Region between 2010 and 2013. These patients were divided into two groups da Vinci and video-assisted thoracoscopic surgery (VATS) according to the selection of the treatments. The time in surgery, intraoperative blood loss, postoperative drainage amount within three days after surgery, the period of bearing drainage tubes, hospital stays and hospitalization expense were then compared. RESULTS: All patients were successfully operated, the postoperative recovery is good and there is no perioperative death. The different of the time in surgery between two groups is Robots group 82 (20-320) min and thoracoscopic group 89 (35-360) min (P>0.05). The intraoperative blood loss between two groups is robot group 10 (1-100) mL and thoracoscopic group 50 (3-1,500) mL. The postoperative drainage amount within three days after surgery between two groups is robot group 215 (0-2,220) mL and thoracoscopic group 350 (50-1,810) mL. The period of bearing drainage tubes after surgery between two groups is robot group 3 (0-10) d and thoracoscopic group: 5 (1-18) d. The difference of hospital stays between two groups is robot group 7 (2-15) d and thoracoscopic group 9 (2-50) d. The hospitalization expense between two groups is robot group (18,983.6±4,461.2) RMB and thoracoscopic group (9,351.9±2,076.3) RMB (All P<0.001). CONCLUSIONS: The da Vinci robot system is safe and efficient in the treatment of mediastinal lesions compared with video-assisted thoracoscopic approach, even though its expense is higher.

[Clinical experience of the treatment of solitary pulmonary nodules with Da Vinci surgical system].

BACKGROUND: A solitary pulmonary nodule (SPN) is defined as a round intraparenchimal lung lesion less than 3 cm in size, not associated with atelectasis or adenopathy. The aim of this study is to learn clinical experience of the treatment of SPN with Da Vinci Surgical System. METHODS: A total of 9 patients with solitary pulmonary nodules (SPN) less than 3 cm in diameter was treated with Da Vinci Surgical System (Intuitive Surgical, California) in thoracic surgery department from General Hospital of Shenyang Militrary Region from November 2011 to March 2014. This group of patients included 3 males and 6 females, and the mean age was 51±9.9 yr (range: 41-74 yr). Most of the patients were no obvious clinical symptoms (7 cases were found by physical examination, others were with cough and expectoration). Their median medical history was 12 mo (range: 4 d-3 yr). All the lesions of patients were peripheral pulmonary nodules and the mean diameter of those was (1.4±0.6) cm(range: 0.8-2.8 cm). Wedge-shaped resection or lobectomy was performed depending on the result of rapid pathology and systemic lymph node dissection was done for malignant leision. We used general anesthesis with double lumens trachea cannula. We set the patients in lateral decubitus position with jackknife. The patient cart enter from top of the patient. The position of trocars would be set according to the position of lesion. A 12 mm incision was positioned at the 8th intercostal space in the posterior axillary line as vision port, and two 8 mm incisions were positioned at the 5th intercostal space between the anterior axillary line and midclavicular line, and the 8th infrascapular line as robotic instrument ports about 10 cm apart from the vision port. One additional auxiliary small incision for instrument without retracting ribs was set at the 7th intercostal space in the middle axillary line. RESULTS: There were 4 benign leisions and 5 malignancies identified. Wedge-shaped resection was performed for 4 patients, lobectomy with systemic lymph node dissection for 3 patients (including 2 right middle lobectomies and 1 left upper lobectomy) and wedge-shaped resection with systemic lymph node dissection for 2 patients of poor lung function. All of the 9 cases were completed with total robotic procedure without conversion. The pathological results included 3 inflammatory pseudotumors, 1 hamartoma, 5 adenocarcinomas. All of the 29 patients were hospital discharged smoothly. The patients were followed up for 0.1-18.5 mo (median 11 mo) without recurrence or metastasis. CONCLUSIONS: The SPN patients should be given active surgical treatments to improve the diagnose rate as well as the cure rate of early non-small cell lung cancer. Since da Vinci Surgical System is a safe and minimally invasive treatment for SPN, it has higher value to the diagnosis and treatment of SPN.