Thoracic Cancer最新文献

Purpose: This study aimed to compare the efficacy of anlotinib plus whole-brain radiotherapy (WBRT) with that of WBRT alone in non-small cell lung cancer (NSCLC) patients with multiple brain metastases (BMs).

Methods: The clinical data of patients with NSCLC and multiple BMs who received WBRT between 2019 and 2022 were collected. The patients were assigned to anlotinib plus WBRT group and WBRT group according to the treatment used.

Results: A total of 64 patients were eligible for analysis; 21 were treated with anlotinib plus WBRT, and 43 were treated with WBRT. The anlotinib plus WBRT group had a greater proportion of patients who were young and had a better performance status and adenocarcinoma histology than did the WBRT group. The median follow-up time was 18.0 months. The median intracranial progression-free survival (iPFS) was significantly longer in the anlotinib plus WBRT group than in the WBRT group (12.9 months vs. 7.4 months, p = 0.004). The median overall survival (OS) was 14.6 months in the anlotinib plus WBRT group and 9.4 months in the WBRT group (p = 0.039). Considering death as a competing risk to intracranial progression, the 1-year cumulative incidence of intracranial progression in the anlotinib plus WBRT group (26.7%) was significantly lower than that in the WBRT group (64.3%) (p = 0.021). There was no significant difference in treatment-related toxicity between the anlotinib plus WBRT group and the WBRT group.

Conclusion: Compared with WBRT alone, anlotinib plus WBRT might confer superior intracranial PFS for NSCLC patients with multiple BMs without increasing treatment-related toxicity.

Background: The cancer cell marker poliovirus receptor-like protein 4 (PVRL4) has been shown to be highly expressed in many cancers, including lung cancer. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells with immunosuppressive roles that can attenuate the anticancer response. Here, the precise functions and the relationship between PVRL4 and MDSCs in lung adenocarcinoma (LUAD) progression were investigated.

Methods: Detection of levels of mRNAs and proteins was conducted using qRT-PCR and western blotting. The CCK-8, colony formation, transwell, wound healing assays, and flow cytometry were used to explore cell growth, invasion, migration, and apoptosis, respectively. ELISA analysis detected TGF-β1 contents. LUAD mouse models were established for in vivo assay. Exosomes were isolated by ultracentrifugation. MDSCs were induced from peripheral blood mononuclear cells (PBMCs) by cytokine or co-culture with cancer cells.

Results: LUAD tissues and cells showed high PVRL4 expression, and PVRL4 deficiency suppressed LUAD cell proliferation, invasion, migration, and induced cell apoptosis in vitro, and impeded LUAD growth in vivo. Thereafter, we found that PVRL4 was packaged into exosomes in LUAD cells, and could be transferred into PBMCs to promote MDSC induction and the expression of MDSC-secreted TGF-β1. Functionally, the silencing of exosomal PVRL4 impaired LUAD cell proliferation, invasion, migration, and evoked cell apoptosis, which could be reversed by the incubation of TGF-β1-overexpressed MDSCs.

Conclusion: Exosomal PVRL4 promoted LUAD progression by inducing the secretion of TGF-β1 in MDSCs, indicating a novel direction for LUAD immunotherapy.

Introduction: Small cell lung cancer (SCLC) is known for its high proliferative rate and poor prognosis. Although Delta-like ligand 3 (DLL3) is specifically expressed on the surface of SCLC, the association of DLL3 with prognosis in SCLC remains uncertain. Hence, we aimed to evaluate prognostic role of DLL3 in extensive stage of SCLC treated with first-line chemotherapy.

Materials and methods: A total of 54 patients with extensive stage of SCLC (ES-SCLC) who were treated with first-line chemotherapy were included for our analysis. In addition, tissue specimen should be available for immuno-histochemical staining for DLL3, and their clinico-pathologic data, including progression-free survival (PFS) and overall survival (OS), were obtained. DLL3 expression and the percentage of tumor cells with DLL3 positive among total cancer cells were analyzed microscopically and DLL3 high and DLL3 low were defined as the percentage of DLL3 positive tumor cells versus total cancer cells ≧ 75% and < 75%, respectively.

Results: DLL3 expression was not associated with any of the clinico-pathological characteristics such as age at diagnosis, sex, response to first-line chemotherapy, second-line chemotherapy (Yes or No), and number of metastatic sites. However, response to first-line chemotherapy and number of metastatic sites were correlated to PFS, while DLL3 expression and number of metastatic sites were correlated to OS.

Conclusion: DLL3 was highly expressed in SCLC, and not associated with any clinico-pathological characteristics. In survival outcome, DLL3 was correlated with worse OS, which suggests the prognostic role of DLL3 in ES-SCLC.

Background: Our study aimed to explore the specific functions and potential mechanisms of miR-224-5p in non-small cell lung cancer (NSCLC).

Methods: We first analyzed the expression of miR-224-5p in NSCLC patients and cell lines through the GEO database and qRT-PCR analysis. Then, we used MTT assays, wound healing assays, Transwell assays, and western blotting to evaluate the effects of miR-224-5p on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we used a xenograft tumor model to evaluate the effect of miR-224-5p on NSCLC tumor growth. Potential binding targets of miR-224-5p were further identified through the target prediction databases, and the relationships between miR-224-5p, its targets, and downstream signaling pathways were further verified using luciferase reporter gene assays and western blotting.

Results: The GEO database and qRT-PCR analysis indicated that miR-224-5p was significantly downregulated in NSCLC patients and cell lines. Functional assays indicated that inhibiting miR-224-5p could enhance the proliferation, migration, invasion, and EMT of NSCLC cells, as well as accelerate tumor growth. In contrast, overexpression of miR-224-5p inhibited these processes. We identified IL6ST (interleukin 6 signal transducer) as a binding target of miR-224-5p. We observed that miR-224-5p could bind to and inhibit IL6ST expression and JAK2/STAT3 signaling pathway, and the inhibition of NSCLC tumor growth and JAK2/STAT3 pathway by miR-224-5p could be reversed by IL6ST overexpression.

Conclusion: Our study demonstrated that miR-224-5p inhibited NSCLC by targeting IL6ST, thereby downregulating the JAK2/STAT3 signaling pathway.

Objectives: This study aimed to analyze lymph node metastasis (LNM) distribution in superficial esophageal squamous cell carcinoma (ESCC) and its impact factors on survival.

Methods: We reviewed 241 pT1N+ ESCC cases between February 2012 and April 2022 from 10 Chinese hospitals with a high volume of esophageal cancer (EC). We analyzed clinicopathological data to identify overall survival (OS) risk factors and LNM distribution in relation to tumor invasion depth.

Results: Of the 241 patients, 26 (10.8%) had pT1a cancer and 215 (89.2%) had pT1b cancer. We showed that N3 stage, ≤ 28 lymphadenectomies, and nerve infiltration (NI) were negative factors for OS in superficial pN+ ESCC, whereas the OS was not definitively affected by the tumor depth and the choice of adjuvant therapy. In general, the LNM rates of the 193 pT1N+ ESCC cases can be ranked in the following order: station 106recR > station 106recL > station 1 > station 7 > station 2. With deeper tumor invasion, the higher LNM rate was observed near the bilateral recurrent laryngeal nerves (RLN), but there was no statistically significant difference.

Conclusions: In superficial ESCC, LNM was frequently observed along the 106recR (35.8%) and 106recL (25.6%) stations. Advanced N-staging (N3) was a major negative impact factor in prognosis, and adequate lymph nodes dissected (LND) (N > 28) improved OS of pT1N+ ESCC. However, in superficial ESCC, tumor infiltration depth did not affect patients' OS or the distribution of positive LNs. The optimal adjuvant treatment that favors survival for these patients required further investigation.

Chronic obstructive pulmonary disease (COPD) is confirmed as an independent risk factor for the development of lung cancer. Although low-dose CT screening significantly reduces the mortality rate of lung cancer, the misdiagnosis and missed diagnosis rates remain high in the COPD population. Additionally, several COPD patients are unable to undergo invasive histological examinations. Therefore, there is an urgent need for minimally invasive biomarkers to screen or diagnose lung cancer in COPD patients. In this study, peripheral blood samples were collected from COPD patients with and without lung cancer. Plasma exosomes (EVs) were extracted for proteomic analysis. Sixteen differentially expressed proteins (DEPs) were preliminarily selected via label-free quantification (LFQ) proteomic technology and comprehensive bioinformatics analysis. Parallel reaction monitoring (PRM) targeted validation identified five candidate proteins associated with COPD with lung cancer. Compared to the COPD group, KRT1, KRT9, and KRT10 were significantly upregulated in the COPD with lung cancer group, while GPLD1 and TF were downregulated. The biomarkers identified in our study provide a foundation for non-invasive screening and diagnosis of lung cancer in COPD patients and exploration of the mechanisms shared between COPD and lung cancer.

Introduction: Studies have shown the antitumor efficacy of immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BM). However, it is unclear whether the efficacy of ICI is similar between patients with and without BM. It is yet unclear whether the efficacy of ICI in patients with BM increases with higher levels of programmed cell death-ligand 1 (PD-L1) expression, as observed in patients without BM.

Methods: We compared the outcomes of ICI treatment between patients with and without BM using a cohort containing 1741 prospectively enrolled patients with lung cancer. We investigated whether there were differences in the outcomes of ICI based on PD-L1 expression levels between these patients.

Results: We enrolled 240 patients with NSCLC with or without BM who were treated with ICI or both chemotherapy and ICI. There were no significant differences in overall survival (OS) between all patients with or without BM (p = 0.489). However, OS was significantly shorter in patients with BM than in those without in the PD-L1 ≥ 50% group (16.5 M vs. 30.6 M, p = 0.003) but not in the PD-L1 ≥ 1% or negative group. BM was an independent poor prognostic factor for OS (hazard ratio: [95% confidence interval], 2.045; [1.058-3.953], p = 0.033) in the PD-L1 ≥ 50% group.

Conclusion: Our study indicated that the outcomes of patients with or without BM treated with ICI were not significantly different. The efficacy of ICI in patients with PD-L1 expression ≥50% would be lower in patients with BM than in those without.

Introduction: Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed.

Methods: We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed.

Results: The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant.

Conclusion: Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

Objective: To conduct a comparative analysis of clinicopathological data between mucinous micropapillary breast carcinoma (MUMPC) and pure mucinous carcinoma (PMC) without a micropapillary structure to elucidate the distinctive clinicopathological characteristics of MUMPC and their impact on prognosis.

Methods: This retrospective analysis included 325 patients diagnosed with mammary mucinous carcinoma admitted to Tianjin Cancer Hospital between July 2014 and December 2019, including 197 patients with MUMPC and 128 patients with PMC without a micropapillary structure. Clinicopathological features were compared, and factors influencing the prognosis of MUMPC were analyzed. Survival analysis was conducted using the Kaplan-Meier method, and univariate and multivariate prognostic analyses for MUMPC were performed using the Cox proportional hazard regression model.

Results: The median follow-up period was 76 months. In the MUMPC and PMC groups, the disease-free survival (DFS) rates at 3, 5, and 7 years were 95.4%, 90.4%, 89.8%, and 100%, 98.4%, and 96.9%, respectively, with a statistically significant difference between the two groups (p = 0.009). Tumor, node, and metastasis (TNM) stage, lymph node metastasis, and endocrine treatment were significant factors influencing the prognosis of the MUMPC group (p < 0.001). Multivariate analysis revealed that lymph node metastasis and endocrine therapy were independent prognostic factors in patients with MUMPC (p < 0.001). Compared with PMC, the MUMPC group exhibited a higher prevalence of HER2 (11.2% vs. 3.1%, p = 0.009) and Ki-67 overexpression (79.7% vs. 60.2%, p < 0.001).

Conclusion: The lymph node stage is the most crucial clinicopathological feature of MUMPC. Endocrine treatment strategy is an independent risk factor affecting the prognosis of MUMPC.