Comprehensive analysis and validation reveal DEPDC1 as a potential diagnostic biomarker associated with tumor immunity in non-small-cell lung cancer.

Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets. Meanwhile, the summary receiver operating characteristic (sROC) curve analysis result showed that DEPDC1 had a high diagnostic value in NSCLC (AUC = 0.96, 95% CI: 0.94-0.98; diagnostic odds ratio = 99.08, 95%CI: 31.91-307.65; sensitivity = 0.89, 95%CI: 0.81-0.94; specificity = 0.92, 95%CI: 0.86-0.96; positive predictive value = 0.94, 95%CI: 0.89-0.98; negative predictive value = 0.78, 95%CI: 0.67-0.90; positive likelihood ratio = 11.77, 95%CI: 6.11-22.68; and negative likelihood ratio = 0.12, 95%CI: 0.06-0.22). Subsequently, quantitative real-time PCR (qRT-PCR) and western blotting indicated that DEPDC1 was high expressed in NSCLC cells. According to the in vitro MTS and apoptotic assays, downregulated DEPDC1 expression targeting P53 signaling pathway inhibited the proliferation of NSCLC cells while promoting apoptosis of NSCLC cells. Moreover, DEPDC1 was significantly correlated with immune cell infiltrating levels in NSCLC based on TCGA data, which were primarily associated with T cells CD4 memory activated, macrophages M1, B cells memory, mast cells resting, T cells regulatory, monocytes, and T cells CD4 memory resting. Compared with the group with high expression of DEPDC1, the group with low expression level had higher scores for immune checkpoint inhibitors (ICIs) treatment. GSEA confirmed that DEPDC1 was involved in gene expression and tumor-related signaling pathways. Finally, DEPDC1 and its associated immune-related genes were shown to be enriched in 'receptor ligand activity', 'external side of plasma membrane', 'regulation of innate immune response', and 'Epstein-Barr virus infection' pathways. The present study demonstrates that DEPDC1 may contribute to NSCLC tumorigenesis and can be applied as the biomarker for diagnosis and immunology.

Comparison between next-generation sequencing and multiplex polymerase chain reaction assays for nonsmall-cell lung cancer molecular diagnosis.

PURPOSE: Genetic mutation detection has become an important step in nonsmall-cell lung cancer (NSCLC) treatment because of the increasing number of drugs that target genomic rearrangements. A multiplex test that can detect multiple gene mutations prior to treatment is thus necessary. Currently, either next-generation sequencing (NGS)-based or polymerase chain reaction (PCR)-based tests are used. We evaluated the performance of the Oncomine Dx Target Test (ODxTT), an NGS-based multiplex biomarker panel test, and the AmoyDx Pan Lung Cancer PCR Panel (AmoyDx PLC panel), a real-time PCR-based multiplex biomarker panel test. MATERIALS AND METHODS: Patients with histologically diagnosed NSCLC and a sufficient sample volume to simultaneously perform the AmoyDx PLC panel and ODxTT-M were included in the study. The success and detection rates of both tests were evaluated. RESULTS: Biopsies revealed 116 cases of malignancies, 100 of which were NSCLC. Of these, 59 met the inclusion criteria and were eligible for analysis. The success rates were 100% and 98% for AmoyDx PLC panel and ODxTT-M, respectively. Nine driver mutations were detected in 35.9% and 37.3% of AmoyDx PLC and ODxTT-M panels, respectively. EGFR mutations were detected in 14% and 12% of samples using the AmoyDx PLC panel and ODxTT-M, respectively. Of the 58 cases in which both NGS and AmoyDx PLC panels were successful, discordant results were observed in seven cases. These differences were mainly due to different sensitivities of the detection methods used and the gene variants targeted in each test. DISCUSSION: The AmoyDx PLC panel, a PCR-based multiplex diagnostic test, exhibits a high success rate. The frequency of the nine genes targeted for treatment detected by the AmoyDx PLC panel was comparable to the frequency of mutations detected by ODxTT-M. Clinicians should understand and use the AmoyDx PLC panel and ODxTT-M with respect to their respective performances and limitations.

Six-Gene Signature for Differential Diagnosis and Therapeutic Decisions in Non-Small-Cell Lung Cancer-A Validation Study.

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic-therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

Biphenotypic lung carcinoma with coexpression of TTF-1 and ΔNP63/P40 within most of the same individual cells: a further case confirming poor prognosis and a review of literature.

The WHO Classification of Tumors, Thoracic Tumors, 5th edition, has outlined the use of TTF-1 and ΔNP63/P40 to discriminate between adenocarcinoma and squamous cell carcinoma. In 2015, the first description of a rare non-small cell lung carcinoma featuring co-expression of glandular and squamous differentiation within most of the same individual tumor cells was reported on, with ultrastructural and molecular demonstration of such a biphenotypic differentiation. We herein describe an additional case of this rare tumor entity, which is confirmed to be an aggressive neoplasm despite potential targets of therapy.

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data.

BACKGROUND: Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta's biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. METHODS: In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. RESULTS: Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. CONCLUSIONS: We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.

Lung cancer outcomes in the elderly: potential disparity in screening.

OBJECTIVES: The aim of this study was to analyse outcomes of lung cancer in the elderly. METHODS: A retrospective analysis was performed of patients in the National Cancer Database with NSCLC from 2004 to 2017 grouped into 2 categories: 70-79 years (A) and 80-90 years (B). Patients with multiple malignancies were excluded. Kaplan-Meier curves estimated the overall survival for each age group based on stage. RESULTS: In total, 466 051 patients were included. Less-invasive techniques (imaging and cytology) diagnosed cancer as a function of age: 14.6% in A vs 21.3% in B [P < 0.001, standardized mean difference (SMD) 0.175]. Clinical stage IA was least common in B (15%) compared to 17.3% in A (P < 0.001, SMD 0.079). Approximately 83.0% in B did not receive surgery compared to 70.0% in A (P < 0.001, SMD 0.299). Of the 83.0%, 8.0% were considered poor surgical candidates because of age or comorbidities compared with 6.2% in A (P < 0.001, SMD 0.299) For 71.0% in B, surgery was not the first treatment plan compared to 62.0% in A (P < 0.001, SMD 0.299). Survival curves showed worse prognosis for each clinical and pathologic stage for B compared to A. CONCLUSIONS: Patients older than 80 years present less frequently as clinical stage IA, are less commonly offered surgical intervention and are more frequently diagnosed using less accurate measures. They also have worse outcomes for each stage compared to younger patients.

Validation of an Updated Algorithm to Identify Patients With Incident Non-Small Cell Lung Cancer in Administrative Claims Databases.

PURPOSE: Real-world lung cancer data in administrative claims databases often lack staging information and specific diagnostic codes for lung cancer histology subtypes. This study updates and validates Turner's 2017 treatment-based algorithm using more recent claims and electronic health record (EHR) data. METHODS: This study used Optum's deidentified Market Clarity Data of linked medical and pharmacy claims with EHR data. Eligible patients had an incident lung cancer diagnosis (January 2014-December 2020) and ≥one valid histology code for lung cancer 30 days before to 60 days after diagnosis. Histology and stage information from the EHR were used to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We evaluated the Turner algorithm using cohort 1 patients diagnosed between June 2014 and October 2015 (step 1) and between November 2015 and December 2020 after approval of immunotherapies (step 2). Next, we evaluated cohort 2 patients diagnosed between November 2015 and December 2020 using an updated algorithm incorporating the latest US treatment guidelines (step 3), and compared the results for cohort 2 (Turner algorithm, step 2 patients). Furthermore, an algorithm to determine early NSCLC (eNSCLC; stage I-III) versus metastatic or advanced/metastatic non-small cell lung cancer (stage IV) was evaluated among patients with available histology and stage information. RESULTS: A total of 5,012 patients were included (cohort 1, step 1: n = 406; cohort 1, step 2: n = 2,573; cohort 2, step 3: n = 2,744). The updated algorithm showed improved performance relative to the previous Turner algorithm for sensitivity (0.920-0.932), specificity (0.865-0.923), PPV (0.976-0.988), and NPV (0.640-0.673). The eNSCLC algorithm showed high specificity (0.874) and relatively low sensitivity (0.539). CONCLUSION: An updated treatment-based algorithm identifying patients with incident NSCLC was validated using EHR data and distinguished lung cancer subtypes in claims databases when EHR data were not available.

Insulin resistance in NSCLC: unraveling the link between development, diagnosis, and treatment.

Lung cancer is responsible for the highest number of cancer-related deaths, with non-small cell lung cancer (NSCLC) being the most prevalent subtype. A critical aspect of managing lung cancer is reducing morbidity and mortality rates among NSCLC patients. Identifying high-risk factors for lung cancer and facilitating early diagnosis are invaluable in achieving this objective. Recent research has highlighted the association between insulin resistance and the development of NSCLC, further emphasizing its significance in the context of lung cancer. It has been discovered that improving insulin resistance can potentially inhibit the progression of lung cancer. Consequently, this paper aims to delve into the occurrence of insulin resistance, the mechanisms underlying its involvement in lung cancer development, as well as its potential value in predicting, assessing, and treating lung cancer.

Clinical utility of the Oncomine Dx Target Test multi-CDx system and the possibility of utilizing those original sequence data.

BACKGROUND: Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi-CDx System has emerged as a prominent companion diagnostic method. However, its efficacy in detecting driver gene mutations, particularly rare mutations, warrants investigation. AIMS: This study aimed to assess the performance of the ODxTT in detecting driver gene mutations in NSCLC patients. Specifically, we aimed to evaluate its sensitivity in detecting epidermal growth factor receptor (EGFR) mutations, a key determinant of treatment selection in NSCLC. MATERIALS AND METHODS: We conducted a retrospective analysis of NSCLC patients who underwent testing with the ODxTT at Keio University Hospital between May 2020 and March 2022. Patient samples were subjected to both DNA and RNA tests. Driver gene mutation status was assessed, and instances of missed mutations were meticulously examined. RESULTS: Of the 90 patients, five had nucleic acid quality problems, while 85 underwent both DNA and RNA tests. Driver gene mutations were detected in 56/90 (62.2%) patients. Of the 34 patient specimens, driver mutations were not detected using the ODxTT; however, epidermal growth factor receptor (EGFR) mutations were detected using polymerase chain reaction-based testing in two patients, and a KRAS mutation was detected by careful examination of the sequence data obtained using the ODxTT in one patient. For the above three cases, carefully examining the gene sequence information obtained using the ODxTT could identify driver mutations that were not mentioned in the returned test results. Additionally, we confirmed comparable instances of overlook results for EGFR mutations in the dataset from South Korea, implying that this type of oversight could occur in other countries using the ODxTT. EGFR mutation was missed in ODxTT in Japan (6.3%, 2/32), South Korea (2.0%, 1/49), and overall (3.7%, 3/81). CONCLUSION: Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing.

Expression patterns and prognostic role of m6A RNA methylation regulators in Non-small Cell Lung Cancer.

To investigate the expression pattern and prognostic role of m6A RNA methylation regulators in non-small cell lung cancer (NSCLC), we downloaded data from 422 patients from The Cancer Genome Atlas (TCGA) database. The relationship between the expression levels of m6A RNA methylation regulators and clinicopathological variables of NSCLC was analysed using R language. By analysing glioma data in TCGA, we found that a prognostic risk score model could be constructed based on 18 genes with m6A methylation modification. m6A gene alterations were significantly associated with tumour grade and tumour stage. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression models were used to identify 2 m6A RNA methylation modifiers: IFG2BP2, and METTL14 to construct risk profiles. Based on the risk profile, patients were divided into high-risk and low-risk groups. The overall survival rate of the low-risk group was significantly higher than that of the high-risk group. The results suggest that the prognostic risk score model constructed by m6A methylation regulators can predict the prognosis of glioma patients. IFG2BP2 and METTL14 may be the key m6A methylation regulators involved in the development of NSCLC and can be used as the molecular markers for the prognosis of NSCLC.

Referred molecular testing as a barrier to optimal treatment decision making in metastatic non-small cell lung cancer: Experience at a tertiary academic institution in Canada.

BACKGROUND: Molecular testing is critical to guiding treatment approaches in patients with metastatic non-small cell lung cancer (mNSCLC), with testing delays adversely impacting the timeliness of treatment decisions. Here, we aimed to evaluate the time from initial mNSCLC diagnosis to treatment decision (TTD) following implementation of in-house EGFR, ALK, and PD-L1 testing at our institution. METHODS: We conducted a retrospective chart review of 165 patients (send-out testing, n = 92; in-house testing, n = 73) with newly diagnosed mNSCLC treated at our institution. Data were compared during the send-out (March 2017-May 2019) and in-house (July 2019-March 2021) testing periods. We performed a detailed workflow analysis to provide insight on the pre-analytic, analytic, and post-analytic intervals that constituted the total TTD. RESULTS: TTD was significantly shorter with in-house testing (10 days vs. 18 days, p < 0.0001), driven largely by decreased internal handling and specimen transit times (2 days vs. 3 days, p < 0.0001) and laboratory turnaround times (TAT, 3 days vs. 8 days, p < 0.0001), with 96% of in-house cases meeting the international guideline of a ≤ 10-day intra-laboratory TAT (vs. 74% send-out, p < 0.001). Eighty-eight percent of patients with in-house testing had results available at their first oncology consultation (vs. 52% send-out, p < 0.0001), and all patients with in-house testing had results available at the time of treatment decision (vs. 86% send-out, p = 0.57). CONCLUSION: Our results demonstrate the advantages of in-house biomarker testing for mNSCLC at a tertiary oncology center. Incorporation of in-house testing may reduce barriers to offering personalized medicine by improving the time to optimal systemic therapy decision.

Highly Sensitive Detection of T790 M with a Three-Level Characteristic Current by Thymine-Hg(II)-Thymine in the α-Hemolysin Nanopore.

Sensitive detection of resistance mutation T790 M is of great significance for early diagnosis and prognostic monitoring of non-small-cell lung cancer (NSCLC). In this paper, we showed a highly sensitive detection strategy for T790 M using a three-level characteristic current signal pattern in an α-hemolysin nanopore. A probe was designed that formed a C-T mismatched base pair with wild-type/P and a T-T mismatched with the T790M/P. The T790M/P produced a unique three-level characteristic current signal in the presence of mercury ions(II): first, T790M-Hg2+-P entering the vestibule of α-HL under the transmembrane potential and overhang of probe occupying the ß-barrel, then probe unzipping from the T790M/P, T790 M temporally residing inside the nanocavity due to the interaction with Hg(II), and finally T790 M passing through the ß-barrel. The blocking current distribution was concentrated with a small relative standard deviation of about 3%, and the signal peaks of T790 M and wild-type can be completely separated with a high separation resolution of more than 2.5, which achieved the highly sensitive detection of T790 M down to 0.001 pM (confidence level P 95%) with a linear range from 0.001 pM to 1 nM in human serum samples. This highly sensitive recognition strategy enables the detection of low abundance T790 M and provides a method for prognostic monitoring in NSCLC patients.

Prognostic and clinicopathological value of osteopontin expression in non-small cell lung cancer: a meta-analysis and systematic review.

BACKGROUND: Although Osteopontin (OPN) has been reported to be associated with many different human cancers, the data on non-small cell lung cancer (NSCLC) are not definitive. This study aimed to explore the prognostic effect of OPN expression and clinicopathological characteristics in patients with NSCLC. METHODS: This study followed all aspects of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report. PubMed, Embase and the Cochrane Library were searched to identify the relative studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the prognostic value of the OPN in patients with NSCLC. The odds ratio (OR) was calculated to represent the relationship between OPN expression and clinicopathological parameters. RESULTS: A total of fifteen studies with 2173 participants were finally included. The results revealed that high expression of OPN was significantly associated with poorer overall survival (OS) (HR = 1.89; 95%CI = 1.68-2.11; p < 0.001). Moreover, a significant correlation was observed between increased OPN expression and poorly differentiated (well and moderately differentiated vs. poorly differentiated; pooled OR = 0.38; 95% CI = 0.23-0.64; p < 0.001), lymph node metastasis (absence vs. presence; pooled OR = 0.49; 95%CI = 0.32-0.74; p < 0.001), and distant metastasis (absence vs. presence; pooled OR = 0.18; 95%CI = 0.11-0.29; p < 0.001). CONCLUSION: This meta-analysis implies that OPN might be a valuable biomarker for a poor prognosis and poor clinicopathological outcomes for patients with NSCLC.

Our findings suggest that osteopontin is an important biomarker for poor prognosis and poor clinicopathological outcome in Non-small cell lung cancer (NSCLC) patients.Increased expression of osteopontin in NSCLC patients is associated not only with poorer survival but also with tumor differentiation, lymph node metastasis, and distant metastasis.This may be due to that osteopontin promotes multiple pathological processes including cancer cell proliferation, invasion, tumor progression, and metastasis in NSCLC.

CircBRIP1: a plasma diagnostic marker for non-small-cell lung cancer.

BACKGROUND: Circular RNA (circRNA), which has been demonstrated in studies to be abundantly prevalent in tumor cells and bodily fluids and to play a significant role in tumors, has the potential for biological markers to be used to assist tumor diagnosis. This study mainly discusses the potential of circBRIP1 as a biomarker for diagnosing non-small-cell lung cancer (NSCLC). METHODS: First, high-throughput sequencing screened the differentially expressed circBRIP1, and real-time fluorescence quantitative PCR (qRT-PCR) verified its expression in NSCLC. Next, sanger sequencing, agarose gel electrophoresis, RNase R assay, and fluorescence in situ hybridization (FISH) were used to verify its molecular characteristics. The diagnostic value was analyzed by the subject operating characteristic curve (ROC), and the cardinality test was analyzed for correlation with clinicopathological parameters. Finally, we tentatively predicted the downstream miRNA- or RNA-binding protein that may bind to circBRIP1. RESULTS: CircBRIP1 is highly expressed in NSCLC tissues, cells and plasma with good specificity and stability. CircBRIP1 not only can well-distinguish NSCLC patients from benign pulmonary diseases (BPD) patients, healthy individuals and small cell lung cancer (SCLC) patients, but it also has some potential for dynamic monitoring. Combined with the analysis of clinicopathological data, the high level of circRNA expression was related to the degree of tumor differentiation, TNM stage, T stage, lymph node metastasis and distal metastasis in NSCLC patients. In addition, circBRIP1 has a high diagnostic value. CONCLUSIONS: Plasma circBRIP1 is significantly overexpressed in NSCLC patients. It can be used as a sensitive biomarker with unique value for early diagnosis, tumor development and prognosis detection.

TEP RNA: a new frontier for early diagnosis of NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers. PURPOSE: Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article. CONCLUSION: The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.

Case report: Clinical complete response in advanced ALK-positive lung squamous cell carcinoma: a case study of successful anti-PD-1 immunotherapy post ALK-TKIs failure.

In patients with advanced lung adenocarcinoma (LADC) harboring the echinoderm microtubule-associated protein-like 4 (EML4) -anaplastic lymphoma kinase (ALK) rearrangement, targeted therapy typically demonstrates superior efficacy as an initial treatment compared to chemotherapy. Following resistance to ALK-tyrosine kinase inhibitors (TKIs), regimens incorporating platinum-based dual agents or combined with bevacizumab often show effectiveness. However, therapeutic alternatives become constrained after resistance develops to both TKIs and platinum-based therapies. Given that the majority of ALK-positive non-small cell lung carcinomas (NSCLC) are LADC, the benefits of TKIs for patients with ALK-positive lung squamous cell carcinoma (LSCC) and the optimal treatment strategy for these patients remain a subject of debate. In this case study, we report on a patient with advanced LSCC, in whom the EML4-ALK rearrangement was identified via ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction). The patient underwent oral treatment with crizotinib and alectinib, showing effectiveness in both first-line and second-line ALK-TKI therapies, albeit with limited progression-free survival (PFS). Subsequent resistance to second-generation TKI was followed by the detection of tumors in the left neck region via computed tomography (CT). Biopsy pathology revealed non-squamous cell carcinoma, and subsequent treatment with platinum-based double-drug therapy proved ineffective. Further analysis through next-generation sequencing (NGS) indicated ALK negativity but a high expression of programmed death-ligand 1 (PD-L1). Immunotherapy was then initiated, resulting in a PFS of over 29 months and clinical complete remission (cCR). This case underscores the potential benefit of ALK-TKIs in patients with ALK-positive LSCC. Resistance to second-generation TKIs may lead to ALK negativity and histological transformation, highlighting the necessity of repeated biopsies post-TKI resistance for informed treatment decision-making. As of November 2023, imaging studies continue to indicate cCR in the patient, with a survival time exceeding 47 months.

Plasma sPD-L1 and VEGF levels are associated with the prognosis of NSCLC patients treated with combination immunotherapy.

The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P  = 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P  = 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HR = 6.834, 95% CI: 1.350-34.592, P  = 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P  = 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HR = 5.911, 95% CI: 1.391-25.122, P  = 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.

Diagnostic and prognostic value of serum soluble B7-H3 in nonsmall cell lung cancer.

The aim of this study was to investigate the utility of serum soluble B7-H3 (sB7-H3) as a diagnostic marker for early-stage nonsmall cell lung cancer (NSCLC) and its potential for evaluating the prognosis of patients with advanced-stage NSCLC. In this study, an ELISA was employed to detect the expression levels of sB7-H3 in a cohort of patients diagnosed with NSCLC ( n = 122) and a control group ( n = 42) during the same observation period. Comparative analyses were conducted to ascertain the variations in sB7-H3 concentrations between the NSCLC cohort and the healthy control group, as well as across pathological types and the presence and absence of lymph node metastasis. (1) The concentration of sB7-H3 in patients diagnosed with NSCLC exhibited a statistically significant increase compared to that observed in the healthy control group ( P < 0.05). Elevated expression levels of sB7-H3 demonstrated a significant correlation with pathological type, lymph node metastasis, tumor, node and metastasis stage and programmed cell death ligand (PD-L1) expression ( P < 0.05). (2) The diagnostic utility of sB7-H3 for the diagnosis of NSCLC and the heightened expression of PD-L1 demonstrated high levels of sensitivity and specificity. (3) Elevated levels of sB7-H3 emerged as an independent risk factor impacting the overall survival of patients diagnosed with advanced NSCLC. The findings of this study suggest that sB7-H3 holds promise as a diagnostic tool for early-stage NSCLC. The elevated expression of sB7-H3 appears to serve as a reliable indicator for assessing the prognosis of patients diagnosed with advanced NSCLC.

[Modern individualized diagnostics and treatment of non-small cell lung cancer]. / Moderne individualisierte Diagnostik und Behandlung des nichtkleinzelligen Lungenkarzinoms.

Approximately one half of patients with non-small cell lung cancer (NSCLC) are diagnosed at resectable tumor stages (I-IIIA), which can potentially be curatively treated. In the early tumor stages (tumor diameter ≤2 cm) sublobar resection (segmentectomy or atypical wedge resection) leads to a 5­year long-term survival comparable to lobectomy. The use of immunotherapy, especially within the framework of neoadjuvant treatment, is anticipated to change the surgical treatment of NSCLC in the future. With the introduction of lung cancer screening for certain risk groups in Germany planned for 2024, lung tumors can be expected to be diagnosed at earlier stages and more frequently curatively treated. This article provides an overview of the potential impact of lung cancer screening, modern minimally invasive surgical techniques and neoadjuvant treatment concepts for the surgical treatment of NSCLC.

The mRNA of solute carrier family 22, member 17 (SLC22A17) plays the potential diagnostic and prognostic role in advantage non-small cell lung cancer patients.

This study aims to evaluate the mRNA levels of solute carrier family 22, member 17 (SLC22A17) and its potential clinical value as a diagnostic and prognostic biomarker in non-small cell lung cancer. This prospective study measured SLC22A17 mRNA levels in lung cancer and paracancer tissues using quantitative reverse transcription-polymerase chain reaction (PCR). The levels of SLC22A17 mRNA in plasma samples from healthy control subjects and patients with lung cancer were also measured. The association between SLC22A17 mRNA levels in plasma and clinicopathological characteristics was determined. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic value of SLC22A17 in plasma. Survival curve analysis was performed using the Kaplan-Meier method. SLC22A17 mRNA levels were significantly higher in lung cancer samples than in the paired paracancerous tissues. Plasma SLC22A17 mRNA levels were also significantly higher in patients with lung cancer than in healthy controls. The COX analysis indicated that there was a significant correlation between elevated plasma SLC22A17 mRNA levels and lymph node metastasis, distant metastasis, and TNM stage. Furthermore, the ROC curve analysis demonstrated that plasma SLC22A17 had high diagnostic value. High plasma SLC22A17 mRNA levels are associated with a significantly shorter survival time. SLC22A17 is upregulated in lung cancer and may serve as a novel diagnostic and prognostic biomarker.