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Background: For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy., Methods: We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia., Results: After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P = .002) and impaired long-term survival (P < .001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group., Conclusions: After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nonsmall cell lung carcinoma (NSCLC) is a major cause of cancer-related death worldwide. The resistance of NSCLC to chemical drugs, such as cisplatin (CDDP), poses a heavy burden for NSCLC therapy. Herein, the effects of circular&#95;0008928 (circ&#95;0008928) on the CDDP sensitivity and biological behavior of CDDP-resistant NSCLC cells and underlying mechanism are revealed. Materials and Methods: The expression of circ&#95;0008928 and microRNA-488 (miR-488) was detected by quantitative real-time polymerase chain reaction. The expression of hexokinase 2 ( HK2 ) protein and exosome-specific proteins was determined by Western blot. The half-maximal inhibitory concentration (IC 50 ) value of CDDP was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and migratory and invasive abilities were illustrated by cell counting kit-8 and transwell assays. Cell glycolysis metabolism was illustrated by extracellular acidification rate assay, glucose kit and lactate kit assays and Western blot analysis. The binding sites between miR-488 and circ&#95;0008928 or HK2 were predicted by starbase or microT-CDS online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ&#95;0008928 expression and HK2 protein expression were significantly upregulated, while miR-488 expression was obviously downregulated in NSCLC cells and CDDP-resistant NSCLC cells. Circ&#95;0008928 expression was increased in serum exosomes of CDDP-resistant NSCLC patients compared with CDDP-sensitive NSCLC patients. In addition, circ&#95;0008928 silencing improved CDDP sensitivity and attenuated CDDP-induced cell proliferation, migration, invasion, and glycolysis metabolism. Circ&#95;0008928 was a sponge of miR-488, and miR-488 bound to HK2 in CDDP-resistant NSCLC cells. Furthermore, both miR-488 inhibitor and HK2 overexpression attenuated circ&#95;0008928 absence-mediated impacts on CDDP sensitivity and tumor process in CDDP-resistant NSCLC. Conclusions: Circ&#95;0008928 knockdown improved CDDP sensitivity and hindered cell proliferation, migration, invasion, and glycolysis metabolism by miR-488/ HK2 axis in CDDP-resistant NSCLC. This finding provides a new mechanism for studying CDDP-resistant therapy in NSCLC.

Objectives: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion., Methods: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates., Results: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy., Conclusions: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Numerous reports have shown that medical treatment confers excellent survival benefits to patients with advanced stage IV non-small cell lung cancer (NSCLC). However, the implications of surgery for primary lesions as palliative treatment remain inconclusive., Methods: We retrospectively extracted clinical data from the Surveillance, Epidemiology, and End Results Program (SEER) database and selected patients with stage IV NSCLC. Patients were classified into non-surgery and surgery groups, and propensity score matching (PSM) analysis was performed to balance the baseline information. Patients in the surgery group, whose overall survival (OS) was longer than the median survival time of those in the non-surgery group, were deemed to benefit from surgery. We evaluated the efficacy of three surgical techniques, namely, local destruction, sub-lobectomy, and lobectomy, on the primary site in the beneficial population., Results: The results of Cox regression analyses revealed that surgery was an independent risk factor for both OS (hazard ratio [HR]: 0.441; confidence interval [CI]: 0.426-0.456; P < 0.001) and cancer-specific survival (CSS) (HR: 0397; CI: 0.380-0.414; P < 0.001). Notably, patients who underwent surgery had a better prognosis than those who did not (OS: P < 0.001; CSS: P < 0.001). Moreover, local destruction and sub-lobectomy significantly compromised survival compared to lobectomy in the beneficial group (P < 0.001). After PSM, patients with stage IV disease who underwent lobectomy needed routine mediastinal lymph node clearing (OS: P = 0.0038; CSS: P = 0.039)., Conclusion: Based on these findings, we recommend that patients with stage IV NSCLC undergo palliative surgery for the primary site and that lobectomy plus lymph node resection should be conventionally performed on those who can tolerate the surgery., (© 2023. The Author(s).)

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC., (© 2022. The Author(s).)

Background: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy., Methods: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation., Results: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status., Conclusion: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome., Methods: Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells. A total of 182 MET IHC+ and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation., Results: MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN≥5 in 4.1% of 1572 patients. MET amplification and MET GCN≥5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (p<0.001). METex14 skipping mutation prevailed in 5 of 182 (2.7%) MET IHC+ WT EGFR/KRAS NSCLC, 4 of which within the 88 adenocarcinomas (4.5%). No association of IHC MET overexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR., Conclusion: MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Comprehensive genomic characterizations of lung squamous cell carcinoma (LSCC) have been performed, but the differences between smokers (S-LSCC) and never smokers (NS-LSCC) are not clear, as NS-LSCC could be considered as a different disease from S-LSCC. In this study we delineated genomic alterations in a cohort of 21 NS-LSCC and 16 S-LSCC patients, and identified common gene mutations and amplifications as previously reported. Inclusion of more NS-LSCC patients enabled us to identify unreported S-LSCC- or NS-LSCC-specific alterations. Importantly, an amplification region containing FGF19, FGF3, FGF4 and CCND1 was found five-times more frequent in S-LSCC than in NS-LSCC. Amplification of FGF19 was validated in independent LSCC samples. Furthermore, FGF19 stimulated LSCC cell growth in vitro. These data implicate FGF19 as a potential driver gene in LSCC with clinic characteristics as smoking.

Background: Growing evidence indicates that miR-200c is involved in carcinogenesis and tumor progression in non-small-cell lung cancer (NSCLC). However, its precise biological role remains largely elusive., Methods: The functions of miR-200c and USP25 in migration/invasion and lung metastasis formation were determined by transwell and tail vein injection assays, respectively. The potential regulatory targets of miR-200c were determined by prediction tools, correlation with target protein expression, and luciferase reporter assay. The mRNA expression levels of miR-200c and USP25 were examined in NSCLC cell lines and patient specimens using quantitative reverse transcription-PCR. The protein expression levels of USP25 were examined in NSCLC cell lines and patient specimens using western blot and immunohistochemical staining., Results: We demonstrated that over-expression of miR-200c inhibited NSCLC cells migration, invasion, epithelial-mesenchymal transition (EMT) in vitro and lung metastasis formation in vivo. Further studies revealed that USP25 was a downstream target of miR-200c in NSCLC cells as miR-200c bound directly to the 3'-untranslated region of USP25, thus reducing both the messenger RNA and protein levels of USP25. Silencing of the USP25 gene recapitulated the effects of miR-200c over-expression. Clinical analysis indicated that miR-200c was negatively correlated with clinical stage, lymph node metastasis in NSCLC patients. Moreover, USP25 protein and mRNA level expressions were higher in NSCLC patients, compared to healthy control, and correlated with clinical stage and lymphatic node metastasis., Conclusions: These findings indicate that miR-200c exerts tumor-suppressive effects for NSCLC through the suppression of USP25 expression and suggests a new therapeutic application of miR-200c in the treatment of NSCLC.

Background: VATS has been extensively considered as a standard method of pulmonary diagnosis and treatment of benign lung diseases. This study aimed to investigate the safety, efficacy, and feasibility of video-assisted thoracoscopic surgery (VATS) lobectomy compared with conventional lobectomy via open thoracotomy in patients with clinical early stage lung cancer., Methods: A total of 120 patients with lung cancer underwent VATS lobectomy; another 120 patients with lung cancer underwent conventional lobectomy. The clinical outcomes from these two groups were retrospectively analyzed and compared., Results: The numbers of patients who underwent lobectomy in the left upper lobe, left lower lobe, right upper lobe, right middle lobe, and right lower lobe were 24, 28, 40, 4, and 24 in the VATS group and 38, 20, 30, 7, and 25 in the conventional group, respectively. No statistical differences were observed between the two groups. Likewise, no statistical differences were observed in terms of duration of operation, time for postoperative extubation, complications, length of hospital stay, and number of dissected lymph nodes (VATS group: left, 5.12 ± 1.45, right, 6.84 ± 1.33; conventional group: left, 4.96 ± 1.39 mm, right, 6.91 ± 1.27; P >0.05)., Conclusion: Anatomical lobectomy was successfully completed by VATS lobectomy for lung cancer; the standard lymph node dissection was also achieved. This procedure also showed advantages in terms of surgical bleeding, duration, postoperative complications, indwelling time of chest tube, and short-term recurrence rate without significant differences from conventional lobectomy.

Background: To evaluate the efficacy of the surgical fat-filling procedure (SFFP) in the treatment of refractory cough and quality of life (QOL) after systematic mediastinal lymphadenectomy in patients with right lung cancer., Methods: This is a blinded, randomized, controlled clinical trial to evaluate refractory cough and QOL in patients after mediastinal lymphadenectomy for lung cancer. One hundred eligible lung cancer patients were randomly divided into two groups: the fat-filling group and non-filling group. In the fat-filling group, post-lymphadenectomy residual cavities (PLRCs) were filled with fatty tissue autografts after lymph node dissection. In the non-filling group, the PLRCs remained unfilled. Clinical endpoints were postoperative cough score and QOL., Results: The SFFP did not increase intraoperative bleeding, extend operation time, or hospital stay. Further, night cough was significantly improved after 4 wk in the fat-filling group after the removal of a chest drainage tube. QOL issues, such as emotional condition, functional status, and additional concerns, demonstrated a remarkable improvement in the fat-filling group at postoperative 1 mo compared with the non-filling (control) group., Conclusions: This study demonstrates that filling PLRCs with fatty tissue autografts is a safe and partially effective treatment for refractory cough after major pulmonary resection and mediastinal lymphadenectomy. This novel procedure significantly improved patient QOL and may prove useful as a relatively safe preventive surgical adjunct operation for refractory cough., (Copyright © 2014 Elsevier Inc. All rights reserved.)

It has been proposed that thioredoxin reductase (TR) is a mediator that allows non-small cell lung cancer (NSCLC) to develop resistance to irradiation; however, little is known regarding the detailed mechanisms of action. Thus, ethaselen {1, 2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)] ethane, BBSKE}, a novel organoselenium TR inhibitor, is currently being investigated in a phase I clinical trial in China. However, its radiosensitizing effect remains unexplored. In this study, we found that the activity of TR increased dramatically in both A549 and H1299 cells after radiation, and moreover, could be inhibited by pretreatment with BBSKE (5 μmol/l). As a TR inhibitor, BBSKE enhanced the efficacy of radiation therapy both in vivo and in vitro without observable toxicity. BBSKE was found to suppress irradiation-induced NF-κB activation dramatically when using A549 cells stably transfected with NF-κB luciferase reporter. These results show the critical role of TR in the radioresistance of NSCLC and suggest that BBSKE is a potentially promising agent for the treatment of patients with NSCLC clinically.

Ethaselen (1, 2-[bis (1, 2-Benzisoselenazolone-3 (2H) -ketone)] ethane, BBSKE), as a novel organoselenium compound targeting thioredoxin reductase (TrxR), has been reported to inhibit tumor growth and TrxR activity in several human tumor cell lines. It has now entered Phase I clinical trails. Here we report the effects of ethaselen and cisplatin (cis-diamminedichloroplatinum II, DDP) combination therapy (ethaselen 36 mg/kg, i.g., o.d. x 10 d and cisplatin 1 mg/kg, i.p., single at day 0) on human A549-grafted nude mouse model (female, BALB/c nude mouse, n = 5, treatment after tumor volume reached 100 mm(3)). Compared to single drug administration (either ethaselen: 36 mg/kg, i.g., o.d. x 10 d or cisplatin: 1.0 mg/kg, i.p., single at day 0), the combination therapy showed significantly reduced tumor size (presumably due to a synergistic effect) and no obvious toxic damage (both in terms of body weight maintenance and liver/kidney damage). These results will be significant in the development of novel anti-tumoral therapeutic strategies directed to non-small cell lung cancer (NSCLC).

Background and Objective: The new edition of the TNM staging for lung and pleural tumours has been finished, which put weight on the extent of primary tumor as one of the important prognosises. But little study has performed on the primary tumor extent < or = 2 cm. The aim of this study is to explore the prognosis of patients with tumor extent < or = 2 cm in stage I of non-small cell lung cancer, which helps us to choose the best treatment for these patients., Methods: Retrospective study on the clinical response and survival time of whom underwent complete surgical resection and diagnosed as T1a of stage I NSCLC from 1998 to 2004 was analyzed. Data was analyzed by SPSS 17.0 software., Results: Overall survival rate was 80.8%. By the study, age (P = 0.241), gender (P = 0.175), history of smoking (P = 0.845), pathologic type ( P =0.265), and systematic mediastinal lymphadenectomy (SML )(P = 0.918) or not, postoperative adjuvant chemotherapy or not ( P = 0.616) and visceral pleural invasion (P = 0.827) were not the prognosises of these patients. Only the tumor differentiation such as poorly differentiated was the important prognosis ( P = 0.01)., Conclusion: In the tumor extent < or = 2 cm of stage I non-small cell lung cancer, the visceral pleural invasion maybe not influence the patients survival. The tumor differentiation is one of the important prognostic factors.