Live tracking of basal stem cells of the epidermis during growth, homeostasis and injury response in zebrafish.

Basal stem cells of the epidermis continuously differentiate into keratinocytes and replenish themselves via self-renewal to maintain skin homeostasis. Numerous studies have attempted to reveal how basal cells undergo differentiation or self-renewal; however, this has been hampered by a lack of robust basal cell markers and analytical platforms that allow single-cell tracking. Here, we report that zebrafish integrin beta 4 is a useful marker for basal cell labelling, irrespective of the body region, stage and regenerative status. We employed Cre-loxP recombination in combination with live cell tracking of single basal clones in the caudal fin and investigated the embryonic origin and behaviour of basal cells during fish growth and homeostasis. Although most basal cells, including those in fins, became quiescent in the adult stage, genetic cell ablation showed that basal cells were reactivated to either self-renew or differentiate, depending on the injured cell type. Our study provides a simple and easy-to-use platform for quantitative in vivo imaging of basal stem cells at wider stages and under various conditions.

Silencing of ZNF610 suppresses cell proliferation and migration in lung adenocarcinoma.

Zinc finger proteins (ZNFs) play a significant role in the initiation and progression of tumors. Nevertheless, the specific contribution of ZNF610 to lung adenocarcinoma (LUAD) remains poorly understood. This study sought is to elucidate the role of ZNF610 in LUAD. Transcript data of LUAD were obtained from The Cancer Genome Atlas Program (TCGA) database and processed via R program. The expression of ZNF610 was assessed in various cell lines. To compare the proliferative capacity of cells with or without ZNF610 silencing, CCK8, cell colony formation assay, and Celigo label-free cell counting assay were employed. Furthermore, transwell migration and invasion assays were conducted to evaluate the migratory and invasive abilities of the cells. The expression levels of genes and proteins were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot techniques. In different LUAD cells, the expression level of ZNF610 was found to be significantly higher in LUAD cells compared to MRC-5 and BASE-2B cells. Moreover, the silencing of ZNF610 resulted in a decrease in cell proliferation and migration abilities. Additionally, the apoptosis rate of cells increased upon silencing ZNF610. Notably, the proportion of cells in the G0/G1 phase increased, while the proportion of cells in the S phase decreased following ZNF610 silencing. Finally, ß-catenin and snail were identified as downstream targets of ZNF610 in cells. Our findings suggest that silencing ZNF610 could inhibit LUAD cell proliferation and migration, possibly through the downregulation of ß-catenin and snail.

A PI3Kγ signal regulates macrophage recruitment to injured tissue for regenerative cell survival.

The interaction between immune cells and injured tissues is crucial for regeneration. Previous studies have shown that macrophages attenuate inflammation caused by injuries to support the survival of primed regenerative cells. Macrophage loss in zebrafish mutants like cloche (clo) causes extensive apoptosis in the regenerative cells of the amputated larval fin fold. However, the mechanism of interaction between macrophage and injured tissue is poorly understood. Here, we show that a phosphoinositide 3-kinase gamma (PI3Kγ)-mediated signal is essential for recruiting macrophages to the injured tissue. PI3Kγ inhibition by the PI3Kγ-specific inhibitor, 5-quinoxalin-6-ylmethylene-thiazolidine-2,4-dione (AS605240 or AS), displayed a similar apoptosis phenotype with that observed in clo mutants. We further show that PI3Kγ function during the early regenerative stage is necessary for macrophage recruitment to the injured site. Additionally, protein kinase B (Akt) overexpression in the AS-treated larvae suggested that Akt is not the direct downstream mediator of PI3Kγ for macrophage recruitment, while it independently plays a role for the survival of regenerative cells. Together, our study reveals that PI3Kγ plays a role for recruiting macrophages in response to regeneration.

LINC01089, suppressed by YY1, inhibits lung cancer progression by targeting miR-301b-3p/HPDG axis.

PURPOSE: LINC01089 is a newly identified lncRNA and rarely reported in human cancers. Our study aimed to investigate its role in lung cancer. METHODS: YY1, LINC01089, and miR-301b-3p levels in lung cancer tissues and cells were assessed using qRT-PCR. Bioinformatics analysis and luciferase reporter, ChIP, and RIP assays were carried out for determining the relationships among YY1, LINC01089, miR-301b-3p, and HPGD. Gain- and loss-of-function assays were carried out to confirm the impacts of LINC01089 and HPDG in lung cancer cells. CCK-8 assay was used to assess cell proliferation rate, and Transwell assay was applied to measure cell invasion and migration. An in vivo tumor model was applied for validating the role of LINC01089. RESULTS: LINC01089 was decreased in lung cancer tissues and cells, and low LINC01089 level predicted a poor clinical outcome. YY1 directly bound to LINC01089 promoter region and inhibited its transcription. LINC01089 knockdown thwarted the proliferation, invasion, and migration capacity of H1299 and A549 cells and aggravated tumor growth. Specifically, LINC01089 functioned as a competing endogenous RNA of miR-301b-3p to modulate HPGD and thereby affected lung cancer progression. CONCLUSION: Our data revealed that LINC01089, directly suppressed by YY1, inhibited lung cancer progression by targeting the miR-301b-3p/HPGD axis. Graphical abstract 1. LINC01089 expression was downregulated in lung cancer tisuues and cell lines, and low LINC01089 levels predicted a poor clinical outcome. 2. LINC01089 knockdown enhanced proliferation, invasion, and migration of H1299 and A549 cells in vitro and promoted lung cancer cell tumorigenesis and metastasis in vivo. 3. LINC01089, directly suppressed by YY1, functioned as a competing endogenous RNA against miR-301b-3p to increase HPGD expression.

MiR-1246 is responsible for lung cancer cells-derived exosomes-mediated promoting effects on lung cancer stemness via targeting TRIM17.

The stemness of lung cancer cells contributes to drug resistance, tumor occurrence, progression, and recurrence; however, the underlying mechanisms are still fragmentary. In the present study, it was found that exosomes from cisplatin-resistant cells and spheres derived from lung cancer cells enhanced the stemness of the parental lung cancer cells. Then we screened the upregulated miRNAs in spheres derived from lung cancer cells and cisplatin-resistant lung cancer cells/exosomes compared to that in the parental lung cancer cells. It was found that miR-1246 was remarkably enriched in cisplatin-resistant lung cancer cells/exosomes and spheres. Additionally, inhibition of miR-1246 attenuated the stemness of lung cancer cells induced by exosomes from cisplatin-resistant cells and spheres. Furthermore, TRIM17 was identified to the direct target of miR-1246 in lung cancer cells. Our findings suggest that exosomal miR-1246 could be as a potential target for lung cancer treatment.

Comparison of Subxiphoid and Intercostal Uniportal Thoracoscopic Thymectomy for Nonmyasthenic Early-Stage Thymoma: A Retrospective Single-Center Propensity-Score Matching Analysis.

OBJECTIVE: The aim of this study was to compare early outcome between intercostal uniportal video-assisted thoracoscopic surgery (IU-VATS) versus subxiphoid uniportal video-assisted thoracoscopic surgery (SU-VATS) in thymectomy for non-myasthenic early-stage thymoma. METHOD: Retrospective analysis of 76 cases completed in our hospital from May 2018 to September 2019 with subxiphoid uniportal thoracoscopic thymectomy; a single incision of ∼3 cm was made ∼1 cm under the xiphoid process. The control group included 213 patients who received intercostal uniportal thoracoscopic thymectomy from August 2015, and propensity score matching was conducted. All patients who were clinically diagnosed with thymic tumor before surgery were treated with thymectomy. Perioperative outcomes between SU-VATS (n = 76) and IU-VATS, n = 76 were compared. RESULT: After propensity score matching, there were no statistically significant differences between the two groups in terms of age, gender, disease stage, maximal tumor size, or other baseline demographic and clinical variables. All operation was successfully completed; there were no significant differences in the operative time (88 vs. 81 minutes, p = 0.63), intraoperative blood loss (55 vs. 46 mL, p = 0.47), postoperative drainage time (2.2 vs. 2.5 days, p = 0.72), and postoperative hospital stay (3.2 vs. 3.4 days, p = 0.78) between the two groups. The visual analog scale (VAS) on postoperative days 1, 3, 7, and 30 was less in the SU-VATS group than that in the IU-VATS group. The VAS on days 60 and 180 did not differ significantly between the two groups. CONCLUSION: Thymectomy using SU-VATS is a feasible procedure; it might reduce early postoperative pain and lead to faster recovery.

Non-intubated uniportal subxiphoid thoracoscopic extended thymectomy for thymoma associated with myasthenia gravis.

BACKGROUND: To describe a technique of non-intubated uniportal subxiphoid thoracoscopic extended thymectomy. METHODS: Data were collected retrospectively. A single 3-cm transverse incision was made below the xiphoid process. This method for extended thymectomy entails adoption of uniportal subxiphoid VATS combined with using of non-intubated anesthesia for thymoma associated with myasthenia gravis. RESULTS: Ten consecutive patients underwent this procedure successfully. Mean operative time was 102.5 min. Conversion to intubated ventilation or thoracotomy was not required. Mean chest tube duration was 3.5 days. Mean postoperative hospital stay was 4.7 days. Histologic examination showed early-stage thymomas. Side effects were rare. Quantitative MG scores decreased during follow-up. CONCLUSIONS: Patients were uneventfully discharged with fast recovery. This technique may merge the potential benefits of a subxiphoid incision and the non-intubated anesthesia protocol.

Nonintubated Uniportal Thoracoscopic Thymectomy with Laryngeal Mask.

OBJECTIVE: To investigate whether laryngeal mask anesthesia had more favorable postoperative outcomes than double-lumen tube intubation anesthesia in uniportal thoracoscopic thymectomy. METHODS: Data were collected retrospectively from December 2013 to December 2017. A total of 96 patients with anterior mediastinum mass underwent nonintubated uniportal video-assisted thoracoscopic thymectomy with laryngeal mask, and 129 patients underwent intubated uniportal video-assisted thoracoscopic thymectomy. A single incision of ∼3 cm was made in an intercostal space along the anterior axillary line. Perioperative outcomes between nonintubated uniportal video-assisted thoracoscopic surgery (NU-VATS) and intubated uniportal video-assisted thoracoscopic surgery (IU-VATS) were compared. RESULTS: In both groups, incision size was kept to a minimum, with a median of 3 cm, and complete thymectomy was performed in all patients. Mean operative time was 61 minutes. The mean lowest SpO2 during operation was not significantly different. However, the mean peak end-tidal carbon dioxide in the NU-VATS group was higher than in the IU-VATS group. Mean chest tube duration in NU-VATS group was 1.9 days. Mean postoperative hospital stay was 2.5 days, with a range of 1 to 4 days. Time to oral fluid intake in the NU-VATS group was significantly less than in the IU-VATS group (p < 0.01). Several complications were significantly less in the NU-VATS group than in the IU-VATS group, including sore throat, nausea, irritable cough, and urinary retention. CONCLUSION: Compared with intubated approach, nonintubated uniportal thoracoscopic thymectomy with laryngeal mask is feasible for anterior mediastinum lesion, and patients recovered faster with less complications.

Tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage.

BACKGROUND: To investigate whether tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage has better short-term outcomes than non-intubated approach with chest tube drainage. METHODS: Data were collected retrospectively from January 2017 and December 2019. Tubeless group included 55 patients with pulmonary nodules underwent tubeless uniportal thoracoscopic wedge resection, 211 patients underwent non-intubated uniportal thoracoscopic wedge resection with chest tube drainage were included in drainage group. Peri-operative outcomes between two groups were compared. RESULTS: After 1:1 matching, 110 patients remained for analysis, baseline demographic and clinical variables were comparable between the two groups. Mean incision size was 3 cm in both group. Mean operative time was 59.3 min in tubeless group and 52.8 min in drainage group. The detectable mean lowest SpO2 and mean peak EtCO2 during operation was acceptable in both groups. Conversion to intubated ventilation or thoracotomy was not required. No patient failed the air leak test and did not undergo a tubeless procedure. Mean postoperative hospital stay was 1.5 days in tubeless group and 2.5 days in drainage group. Residual pneumothorax or subcutaneous emphysema was not frequent and mild in tubeless group. Side effects were rare and mild, including cough and hemoptysis. No re-intervention or readmission occurred. The postoperative VAS score was significantly lower in tubeless group. CONCLUSIONS: Tubeless uniportal thoracoscopic wedge resection with modified air leak test and chest tube drainage is feasible and safe for selected patients with peripheral pulmonary nodules, it might reduce post-operation pain and lead to faster recovery.

Comparison of Postoperative Pain and Recovery between Single-Port and Two-Port Thoracoscopic Lobectomy for Lung Cancer.

OBJECTIVE: To investigate whether the single-port (SP) technique had more favorable postoperative outcomes than had the two-port (TP) technique. METHODS: One hundred sixty-six single-port video-assisted thoracoscopic surgery (SP-VATS) lobectomy and 162 two-port video-assisted thoracoscopic surgery (TP-VATS) lobectomy had been successfully completed between August 2015 and September 2016. A single incision of ∼3 cm was made in an intercostal space along the anterior axillary line. Perioperative outcomes and the safety between SP-VATS and TP-VATS lobectomy for NSCLC was compared. RESULTS: In the SP-VATS group, incision size was kept to a minimum, with a median of 3 cm; mediastinal lymph node dissection was performed in all patients with malignancy. Overall, median operative time was 89 minutes, and median chest tube duration was 3.1 days. The VAS on postoperative days 3, 7, and 14 was less in the SP-VATS group than that in the TP-VATS group. The VAS on days 1, 30, 60, 90, 180, and 360 did not differ significantly between the two groups. The number of days of use of analgesic agents after surgery was less in the SP-VATS group. The pathological symptoms of wound pain were significantly less in the SP-VATS group. CONCLUSIONS: Compared with the multiport approach, SP VATS lobectomy might reduce postoperative pain and lead to faster recovery.

Robust and local positional information within a fin ray directs fin length during zebrafish regeneration.

It has been proposed that cells are regulated to form specific morphologies and sizes according to positional information. However, the entity and nature of positional information have not been fully understood yet. The zebrafish caudal fin has a characteristic V-shape; dorsal and ventral fin rays are longer than the central ones. This fin shape regenerates irrespective of the sites or shape of fin amputation. It is thought that reformation of tissue occurs according to positional information. In this study, we developed a novel transplantation procedure for grafting a whole fin ray to an ectopic position and examined whether the information that specifies fin length exists within each fin ray. Intriguingly, when long and short fin rays were swapped, they regenerated to form longer or shorter fin rays than the adjacent host fin rays, respectively. Further, the abnormal fin ray lengths were maintained for a long time, more than 5 months, and after further re-amputation. In contrast to intra-fin grafting, when fin ray grafting was performed between fish, cells in the grafts disappeared due to immune rejection, and the grafted fin rays adapted to the host position to form a normal fin. Together, our data suggest that the information that directs fin length does exist in cells within a single fin ray and that it has a robust property-it is stable for a long time and is hard to rewrite. Our study highlighted a novel positional information mechanism for directing regenerating fin length.

Bronchoplasty using continuous suture in complete monitor view: a suitable method of thoracoscopic sleeve lobectomy for non-small cell lung cancer.

BACKGROUND: Our study aims to determine the value of bronchial anastomosis using complete continuous suture. METHODS: Six patients diagnosed with central lung carcinoma who were candidates for right-sided sleeve lobectomy and underwent sleeve resection of the right upper lobe by thoracoscopic surgical procedure. RESULTS: The mean surgical time was 182 min (range, 110 to 260 min). The mean time of bronchial anastomosis was 49 min (range, 18 to 76 min). The mean bleeding was 110 mL (range, 50 to 260 mL). Median chest tube drainage was 305 mL (range, 200 to 600 mL). No perioperative deaths or major complications occurred. The postoperative bronchoscopy confirmed no stenosis. The mean follow-up time was 19.2 months (range, 7 to 34 months), and six patients were alive. CONCLUSIONS: Bronchial anastomosis using complete continuous suture may be a suitable method in thoracoscopic sleeve lobectomy.

Ipsilateral partial anomalous pulmonary venous connection in right lung cancer with absent right upper lobe.

A partial anomalous pulmonary venous connection (PAPVC) is an uncommon congenital anomaly. This report documents the case of a 48-year-old man with PAPVC which was incidentally discovered with right lung cancer and absence of right upper lobe. Right pneumonectomy was successfully performed, and the patient had an uneventful postoperative course. Asymptomatic PAPVC without septal defect is extremely rare. If the PAPVC is located in a different lobe, a pulmonary resection for lung cancer would precipitate an adverse outcome without a correction of the PAPVC. Surgeons should therefore be cautious regarding the potential existence of a PAPVC when a patient undergoes surgical procedures.

Advancements in the diagnosis and treatment of sub­centimeter lung cancer in the era of precision medicine (Review).

Lung cancer is the malignancy with the highest global mortality rate and imposes a substantial burden on society. The increasing popularity of lung cancer screening has led to increasing number of patients being diagnosed with pulmonary nodules due to their potential for malignancy, causing considerable distress in the affected population. However, the diagnosis and treatment of sub-centimeter grade pulmonary nodules remain controversial. The evolution of genetic detection technology and the development of targeted drugs have positioned the diagnosis and treatment of lung cancer in the precision medicine era, leading to a marked improvement in the survival rate of patients with lung cancer. It has been established that lung cancer driver genes serve a key role in the development and progression of sub-centimeter lung cancer. The present review aimed to consolidate the findings on genes associated with sub-centimeter lung cancer, with the intent of serving as a reference for future studies and the personalized management of sub-centimeter lung cancer through genetic testing.

Roles of IL-4, IL-13, and Their Receptors in Lung Cancer.

Interleukin (IL)-4 and IL-13 are the main effectors of innate lymphoid cells (ILC2) of the type 2 innate immune response, which can carry out specific signal transmission between multiple cells in the tumor immune microenvironment. IL-4 and IL-13 mediate signal transduction and regulate cellular functions in a variety of solid tumors through their shared receptor chain, the transmembrane heterodimer interleukin-4 receptor alpha/interleukin-13 receptor alpha-1 (type II IL-4 receptor). IL-4, IL-13, and their receptors can induce the formation of a variety of malignant tumors and play an important role in their progression, growth, and tumor immunity. In order to explore possible targets for lung cancer prediction and treatment, this review summarizes the characteristics and signal transduction pathways of IL-4 and IL-13, and their respective receptors, and discusses in depth their possible role in the occurrence and development of lung cancer.

Identification of cytokines in benign and malignant thymus tumors: based on Mendelian randomization and proteomics.

Objective: The aim of this study was to identify potential causal cytokines in thymic malignancies and benign tumors from the FinnGen database using Mendelian randomization (MR). Methods: In this study, data from genome-wide association studies (GWAS) of 91 cytokines were used as exposure factors, and those of thymic malignant tumors and thymic benign tumors were the outcome variables. Two methods were used to determine the causal relationship between exposure factors and outcome variables: inverse variance weighting (IVW) and MR-Egger regression. Sensitivity analysis was performed using three methods, namely, the heterogeneity test, the pleiotropy test, and the leave-one-out test. Results: There was a causal relationship between the expression of fibroblast growth factor 5, which is a risk factor for thymic malignant tumors, and thymic malignant tumors. C-C motif chemokine 19 expression, T-cell surface glycoprotein CD5 levels, and interleukin-12 subunit beta levels were causally related to thymic malignant tumors and were protective. Adenosine deaminase levels, interleukin-10 receptor subunit beta expression, tumor necrosis factor (TNF)-related apoptosis-inducing ligand levels, and TNF-related activation-induced cytokine levels showed a causal relationship with thymic benign tumors, which are its risk factors. Caspase 8 levels, C-C motif chemokine 28 levels, interleukin-12 subunit beta levels, latency-associated peptide transforming growth factor beta 1 levels, and programmed cell death 1 ligand 1 expression showed a causal relationship with thymic benign tumors, which are protective factors. Sensitivity analysis showed no heterogeneity. Conclusion: Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.

Shared biomarkers and mechanisms in idiopathic pulmonary fibrosis and non-small cell lung cancer.

BACKGROUND: Epidemiological evidence has indicated the occurrence of idiopathic pulmonary fibrosis (IPF) with coexisting lung cancer is not a coincidence. The pathogenic mechanisms shared between IPF and non-small cell lung cancer (NSCLC) at the transcriptional level remain elusive and need to be further elucidated. METHODS: IPF and NSCLC datasets of expression profiles were obtained from the GEO database. Firstly, to detect the shared dysregulated genes positively correlated with both IPF and NSCLC, differentially expressed analysis and WGCNA analysis were carried out. Functional enrichment and the construction of protein-protein network were employed to reveal pathogenic mechanisms related to two diseases mediated by the shared dysregulated genes. Then, the LASSO regression was adopted for screening critical candidate biomarkers for two disorders. Moreover, ROC curves were applied to evaluate the diagnostic value of the candidate biomarkers in both IPF and NSCLC. RESULTS: The 20 shared dysregulated genes positively correlated with both IPF and NSCLC were identified after intersecting differentially expressed analysis and WGCNA analysis. Functional enrichment revealed the 20 shared genes mostly enriched in extracellular region, which is critical in the organization of extracellular matrix. The protein-protein networks unrevealed the interaction of the 11 shared genes involving in collagen deposition and the connection between PYCR1 with PSAT1. PSAT1, PYCR1, COL10A1 and KIAA1683 were screened by the LASSO regression. ROC curves comprising area under the curve (AUC) verified the potential diagnostic value of PSAT1 and COL10A1 in both IPF and NSCLC. CONCLUSIONS: We revealed dysregulated extracellular matrix through aberrant expression of the relevant genes, which provided further understanding for the common molecular mechanisms predisposing the occurrence of both IPF and NSCLC.

Evidence based on Mendelian randomization: Causal relationship between mitochondrial biological function and lung cancer and its subtypes.

OBJECTIVE: This study aimed to investigate the causal relationship between mitochondrial biological function and lung cancer, including its subtypes, via MR. METHODS: SNPs significantly associated with lung cancer and its subtypes were employed as instrumental variables. MR-Egger regression, simple mode, weighted mode, simple median, and weighted median, were utilized to determine the causal relationship between the exposure factor and the occurrence of lung cancer and its subtypes. RESULTS: NADH dehydrogenase (ubiquinone) flavoprotein 2 and transmembrane protein 70 were found to have a causal relationship with lung adenocarcinoma, acting as protective factors. The causal relationship between mitochondrial import inner membrane translocase subunit and NADH dehydrogenase (ubiquinone) iron-sulfur protein 4 and small-cell lung cancer was established as a risk factor. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 exhibited a causal relationship with small-cell lung cancer, acting as a protective factor. Furthermore, NAD-dependent protein deacylase sirtuin-5 was causally linked to lung squamous cell carcinoma, serving as a protective factor. A funnel plot demonstrated the symmetrical distribution of the SNPs. Thew pleiotroy test (P > 0.05) and "leave-one-out" test validated the relative stability of the results. CONCLUSION: This study established a causal relationship between mitochondrial biological function and lung cancer, including its subtypes.

Identification of pathogenic germline variants in a large Chinese lung cancer cohort by clinical sequencing.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large-scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer-susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next-generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer-susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case-control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair-associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification.