Thoracic Cancer最新文献

Background: Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP-ribose) polymerase (PARP) inhibitors or breast cancer treatment with first-line platinum-based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker.

Methods: We studied the relationship between HRD status and the effectiveness of first-line ICI-based therapy in EGFR/ALK wild-type metastatic non-small cell lung cancer patients (NSCLC) patients.

Results: This study included 22 treatment naïve NSCLC patients. The HRD score ranged from -26.37 to 92.34, with an average of 24.57. Based on analysis of the progression-free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan-Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (-) (N/A vs. 7.0 ms, log-rank p = 0.029; HR 0.20, 95% CI: 0.04-0.96, likelihood-ratio p = 0.03). In patients with PD-L1 TPS ≥50% and HRD score ≥31 (co-status high), the mPFS was temporarily not reached during the follow-up period. In patients with PD-L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co-status was 0.14 (95% CI: 0.04-0.54), which was a good prognostic factor, and the prognostic effect of co-status was better than that of HRD score alone.

Conclusion: The HRD status can be identified as an independent significance in NSCLC patients treated with first-line ICI-based therapy.

Background: Recent advancements in advanced non-small-cell lung cancer (NSCLC) treatment have significantly improved primary therapy outcomes owing to the emergence of various molecular targeted therapies and immune checkpoint inhibitors (ICIs). However, for Kirsten rat sarcoma viral antigen (KRAS) mutations, molecular targeted drugs, such as sotorasib, are not applicable as first-line treatments, and the optimal primary treatment remains unclear. Therefore, we aimed to investigate the efficacy of ICI combination therapy as first-line treatment for KRAS-mutant NSCLC.

Methods: We conducted a systematic search for phase 3 randomized controlled trials (RCTs) that presented data on KRAS mutation status in advanced NSCLC. The primary endpoints were progression-free survival (PFS) and overall survival (OS). A random-effects network meta-analysis was conducted to perform direct and indirect comparisons among treatment groups.

Results: Six RCTs were eligible for inclusion. In the network meta-analysis for KRAS-mutant NSCLC, Chemo + bevacizumab (Bev) + ICI was associated with improved PFS (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.22-0.64), followed by Chemo + ICI + ICI (HR 0.66, 95% CI 0.47-0.93) and Chemo + ICI (HR 0.67, 95% CI 0.49-0.91). The most beneficial effect on OS was observed with Chemo + Bev + ICI (HR 0.50, 95% CI 0.34-0.73), followed by Chemo + ICI + ICI (HR 0.64, 95% CI 0.48-0.87) and Chemo + ICI (HR 0.72, 95% CI 0.56-0.92). Regarding OS in wild-type KRAS, ICI + ICI (HR 0.73, 95% CI 0.50-1.07) produced the most favorable effects, followed by Chemo + ICI (HR 0.79, 95% CI 0.63-0.99).

Conclusion: The efficacy of Chemo + Bev + ICI is potentially high for improving PFS and OS in KRAS-mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first-line treatment.

Background: Methyltransferase 3 (METTL3) accelerates N6-methyladenosine (m6A) modifications and affects cancer progression, including non-small-cell lung cancer (NSCLC). In this study, we aimed to explore the regulatory mechanisms of METTL3 underling NSCLC.

Methods: Immunohistochemical assay, quantitative real-time polymerase chain reaction (qRT-PCR) assay, and western blot assay were conducted for gene expression. MTT assay and colony formation assay were performed to explore cell proliferation capacity. Cell apoptosis and THP-1 cell polarization were estimated by flow cytometry analysis. Cell migration and invasion capacities were evaluated by transwell assay. Methylated RNA immunoprecipitation assay, dual-luciferase reporter assay, actinomycin D treatment and RIP assay were performed to analyze the relationships of METTL3, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), and transient receptor potential cation channel subfamily V member 1 (TRPV1). The functions of METTL3 and TRPV1 in vivo were investigated through establishing the murine xenograft model.

Results: TRPV1 expression was upregulated in NSCLC and related poor prognosis. TRPV1 silencing inhibited NSCLC cell growth and metastasis, induced NSCLC cell apoptosis, and repressed M2 macrophage polarization. The results showed that METTL3 and IGF2BP1 could regulate TRPV1 expression through m6A methylation modification. Moreover, METTL3 deficiency inhibited NSCLC cell growth, metastasis, and M2 macrophage polarization and facilitated NSCLC cell apoptosis, while TRPV1 overexpression restored the impacts. In addition, METTL3 knockdown restrained tumor growth in vivo via regulating TRPV1 expression.

Conclusion: METTL3 bound to IGF2BP1 and enhanced IGF2BP1's m6A recognition of TRPV1 mRNA, thereby promoting NSCLC cell growth and metastasis, and inhibiting M2 macrophage polarization.

Background: The aim of the present study was to investigate the function of novel circular RNA hsa_circ_0036683 (circ-36683) in non-small cell lung cancer (NSCLC).

Methods: RNA sequencing was used to screen out differentially expressed miRNAs. Expression levels of miR-4664-3p and circ-36683 were evaluated in lung carcinoma cells and tissues by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effects of miR-4664-3p and circ-36683 on proliferation and migration were assessed using cell counting kit-8 (CCK-8), wound healing and transwell migration assays and xenograft experiments. The targeting relationship of circ-36683/miR-4664-3p/CDK2AP2 was assessed by luciferase reporter assays, western blot, qRT-PCR and argonaute2-RNA immunoprecipitation (AGO2 RIP). Co-immunoprecipitation (Co-IP), 5-ethynyl-2'-deoxyuridine (EdU) staining and CCK-8 were used to validate the indispensable role of CDK2AP2 in suppressing cell proliferation as a result of CDK2AP1 overexpression.

Results: By RNA sequencing, miR-4664-3p was screened out as an abnormally elevated miRNA in NSCLC tissues. Transfection of miR-4664-3p could promote cell proliferation, migration and xenograft tumor growth. As a target of miR-4664-3p, CDK2AP2 expression was downregulated by miR-4664-3p transfection and CDK2AP2 overexpression could abolish the proliferation promotion resulting from miR-4664-3p elevation. Circ-36683, derived from back splicing of ABHD2 pre-mRNA, was attenuated in NSCLC tissue and identified as a sponge of miR-4664-3p. The functional study revealed that circ-36683 overexpression suppressed cell proliferation, migration and resulted in G0/G1 phase arrest. More importantly, the antioncogenic function of circ-36683 was largely dependent on the miR-4664-3p/CDK2AP2 axis, through which circ-36683 could upregulate the expression of p53/p21/p27 and downregulate the expression of CDK2/cyclin E1.

Conclusion: The present study revealed the antioncogenic role of circ-36683 in suppressing cell proliferation and migration and highlighted that targeting the circ-36683/miR-4664-3p/CDK2AP2 axis is a promising strategy for the intervention of NSCLC.

Background: Lymph node (LN) metastasis is a significant prognostic factor for esophageal squamous cell carcinoma (ESCC), and there are no satisfactory methods for accurately predicting metastatic LNs. The present study aimed to assess the efficacy of ^99mTc-3PRGD₂ single-photon emission computed tomography (SPECT)/computed tomography (CT) for diagnosing metastatic LNs in ESCC.

Methods: A total of 15 enrolled patients with ESCC underwent ^99mTc-3PRGD₂ SPECT/CT and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET/CT) examinations preoperatively. High-definition bone carving reconstruction technology (HD-xSPECT Bone) was applied to quantitatively assess the LN's SUV_max via SPECT/CT. The two methods were compared for diagnosing metastatic LNs with pathology as the gold standard.

Results: Among 15 patients, 23 metastatic lymph node stations (mLNSs) were predicted by SPECT/CT, with a mean SUV_max of 2.71 ± 1.34, of which 15 were pathologically confirmed; 32 mLNSs were predicted by PET/CT with a mean SUV_max of 4.41 ± 4.02, of which 17 were pathologically confirmed. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of SPECT/CT for diagnosing metastatic LNs were 62.50%, 91.30%, 85.34%, 65.22%, and 90.32%, respectively, and those of PET/CT were 70.83%, 83.70%, 81.03%, 53.13%, and 91.67%, respectively. There was no significant difference in sensitivity (p = 0.061) or specificity (p = 0.058) between the two methods. The AUC_SPECT/CT was 0.816 and the SUV_max threshold was 2.5.

Conclusion: ^99mTc-3PRGD₂ SPECT/CT might be an effective method for diagnosing metastatic LNs in ESCC, especially in combination with HD-xSPECT Bone. The diagnostic efficiency of this method was noninferior to that of ¹⁸F-FDG PET/CT. The SUV_max threshold of 2.5 showed the highest agreement with the pathology findings.

Selpercatinib is the first targeted therapy for rearranged during transfection (RET) fusion-positive unresectable non-small-cell lung cancer (NSCLC). The main adverse effects of selpercatinib include hypertension, liver dysfunction, diarrhea, and QT prolongation on electrocardiograms. However, instances of drug-induced interstitial lung disease (DI-ILD) are infrequently reported. We describe the first case of a patient with RET fusion-positive NSCLC treated with selpercatinib who developed DI-ILD, confirmed pathologically. The patient, a 72-year-old woman, initiated selpercatinib treatment following the postoperative recurrence of lung adenocarcinoma. After 15 months of treatment, computed tomography scans revealed multiple infiltrates and ground-glass opacities in both lungs. A thoracoscopic lung biopsy identified organizing pneumonia, attributed to DI-ILD caused by selpercatinib. Although she was asymptomatic, the patient's selpercatinib treatment was discontinued, leading to a gradual improvement in the lung infiltrates. Despite the lack of detailed reports, DI-ILD with selpercatinib represents a potentially serious adverse event and should be approached with caution.

Background: Patients with non-small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored.

Methods: This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables.

Results: The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD-L1) levels. Furthermore, NSCLC patients with wild-type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis.

Conclusion: In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

Background: Lung cancer is one of the major threats to human life worldwide. MiR-190 has been found to perform essential roles in multiple cancer progression; however, there have been no studies focused on its function and underlying regulatory mechanism in lung cancer.

Method: The miR-190 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The cell functional experiments, including cell counting kit-8 (CCK-8), colony formation and transwell assay were conducted in vitro, as well as animal experiments performed in vivo. The regulation and potential binding sites of CBX4 on miR-190 were predicted by TCGA data set and JASPAR website and verified by ChIP assay and dual-luciferase reporter assay. The prospects binding site of miR-190-3p on CBX4 3'UTR region was predicted by StarBase and verified by dual-luciferase reporter assay.

Results: MiR-190 was decreased in lung cancer cells. The overexpression of miR-190 had no effects on cell proliferation, but significantly inhibited cancer metastasis both in vitro and in vivo. Moreover, miR-190 expression could be transcriptionally inhibited by CBX4, and CBX4 was the direct target of miR-190-3p.

Conclusion: MiR-190 served as a cancer metastasis inhibitor in lung cancer and formed a regulatory loop with CBX4. These findings provided emerging insights into therapeutic targets and strategies for metastatic lung cancer.

Purpose: To evaluate the value of computed tomography (CT)-based radiomics combined with clinical-genetic features in predicting brain metastasis in patients with stage III/IV epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC).

Methods: The study included 147 eligible patients treated at our institution between January 2018 and May 2021. Patients were randomly divided into two cohorts for model training (n = 102) and validation (n = 45). Radiomics features were extracted from the chest CT images before treatment, and a radiomics signature was constructed using the Least Absolute Shrinkage and Selection Operator regression. Kaplan-Meier survival analysis was used to describe the differences in brain metastasis-free survival (BM-FS) risk. A clinical-genetic model was developed using Cox regression analysis. Radiomics, genetic, and combined prediction models were constructed, and their predictive performances were evaluated by the concordance index (C-index).

Results: Patients with a low radiomics score had significantly longer BM-FS than those with a high radiomics score in both the training (p < 0.0001) and the validation (p = 0.0016) cohorts. The C-indices of the nomogram, which combined the radiomics signature and N stage, overall stage, third-generation tyrosine kinase inhibitor treatment, and EGFR mutation status, were 0.886 (95% confidence interval [CI] 0.823-0.949) and 0.811 (95% CI 0.719-0.903) in the training and validation cohorts, respectively. The combined model achieved a higher discrimination and clinical utility than the single prediction models.

Conclusions: The combined radiomics-genetic model could be used to predict BM-FS in stage III/IV NSCLC patients with EGFR mutations.

Although stereotactic body radiotherapy (SBRT) is a curative treatment option for stage I non-small cell lung cancer (NSCLC), limited data are available regarding chest wall (CW) toxicities during an extended follow-up of over 10 years. We report an unusual case of a bone tumor-like CW mass lesion with pathological rib fractures observed 13 years after SBRT for peripheral lung cancer. Despite the initial suspicion of radiation-induced sarcoma, a subsequent incisional biopsy revealed no evidence of malignancy, and a definitive diagnosis of osteonecrosis was made. Thus, long-term observation of over 10 years is required to identify late chronic complications following SBRT.