Clinical and pathological characteristics of 11 NSCLC patients with c-MET exon 14 skipping.

Background: The aim of the present study was to summarize the clinical and pathological characteristics of 11 non-small cell lung cancer (NSCLC) patients with mesenchymal-epithelial transition factor exon 14 skipping (METex14). Methods: From 2018 to 2021, medical records of 763 NSCLC patients were reviewed and 11 patients carrying METex14 were identified from the Affiliated Hospital of Guangdong Medical University. Their clinical data were subsequently examined for pathological and related clinical information including symptom and diagnosis, imaging and follow-up. Results: The METex14 cohort includes 9 males and 2 females and the age range was 69-85 years, with a median age of 77 years. Of the patients one is diagnosed with stage IVB lung adenosquamous carcinoma, 7 with lung adenocarcinoma (1 with stage IIIA and 6 with stage IV), and 3 with stage IV lung sarcomatoid carcinoma. 3 reached stable disease until the end of follow-up and 4 died within a year due to multiple metastases. In 4 cases, the patients received selective MET inhibitor treatment all lived longer than 7 months. There were 4 heterozygous point mutations and 1 deletion of the MET gene in this cohort, as follows: c.G3028T (p.D1010Y); c.G3028A (p.D1010N); c.G3005C (p.V1002A); c.3022C>G and MET c.3021_3028+20del (E14). Conclusions: According to the data that we collected, the incidence of NSCLC carrying METex14 is low and male outnumber female in our sample pool. Selective target therapy had better prognosis than multitargeted tyrosine kinase inhibitor (TKI) such as crizotinib or standard therapy.

The Value of Serum Exosomal miR-184 in the Diagnosis of NSCLC.

Lung cancer has the highest morbidity rate (11.6%) and mortality rate (18.4%) among all current tumors. The morbidity rate in China accounts for approximately one-third, and it is still rising. Nonsmall cell lung cancer is the most common type of lung cancer, accounting for 80%-85% of all lung cancers, and approximately 57% of patients with advanced nonsmall cell lung cancer have distant metastases at the time of diagnosis. To explore the expression changes in microRNA-184 (miR-184) and its clinical value in serum exosomes of patients with nonsmall cell lung cancer (NSCLC). This study adopted a case-control study method, selecting 88 patients (NSCLC group) from June 2015 to June 2017 in our hospital who are confirmed to have NSCLC by fiber-optic bronchoscopy, and 90 patients who are confirmed to have benign lung diseases by pathological examination during the same period (control group). Fluorescence quantitative PCR technology is used to detect the levels of miR-184 in serum exosomes of the two groups, and the differences in the levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics are analyzed. According to the results of the 3-year follow-up, the miR-184 levels in serum exosomes of NSCLC patients are grouped and compared. The expression level of miR-184 in serum exosomes in the NSCLC group is significantly higher than that in the control group, and the difference between the two groups is statistically significant (p < 0.05). The ROC curve is drawn with the expression level of miR-184 in serum exosomes of the two groups of patients. The results showed that the area under the ROC curve for the differential diagnosis of NSCLC and benign lung tumors with the expression level of miR-184 in serum exosomes is 0.927, and the sensitivity is 87.61%, while the specificity is 84.02%. The expression levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics, in different TNM stages [(I+II) vs. (III+IV)], lymph node metastasis (yes vs. no), and different degrees of differentiation [(High + Medium) vs. Poorly differentiated] are compared and showed statistical significance (p < 0.05). In 88 NSCLC patients, after 3 years of follow-up, 33 survived, and 55 died, with a survival rate of 37.50%. The expression of miR-184 in serum exosomes of the 33 surviving patients is significantly lower than that of the nonsurviving group (p < 0.05). The expression level of miR-184 in serum exosomes of NSCLC patients is significantly increased, which has a certain value for the differential diagnosis of the nature of benign and malignant lung diseases and is closely related to the prognosis of patients.

Serum exosomal miR-16-5p functions as a tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in lung adenocarcinoma by regulating PD-L1 expression.

OBJECTIVES: We aimed at investigating whether serum exosomal miR-16-5p could be utilized as an immunotherapy biomarker in lung adenocarcinoma (LUAD) patients administered by programmed cell death ligand-1 (PD-L1) inhibitors, and to evaluate its functions in LUAD progression. METHODS: Sixty LUAD sufferers and 20 healthy controls (HCs) were covered in this work. We applied both IHC and WB to examine PD-L1 level in clinical tissue samples and utilized WB to quantify PD-L1 expression in LUAD cells and LUAD xenograft tissues, respectively. Transmission electron microscopy (TEM), WB, and nanoparticle tracking analysis (NTA) were executed to confirm the exosomes isolated from serum specimens and cell culture media. To quantify of exosomal miR-16-5p level from serum and culture medium of cultured cell, qRT-PCR experiment was utilized. The connection between tissue PD-L1 level and serum exosomal miR-16-5p expression in PD-L1-positive sufferers administered by PD-L1 inhibitors was verified using Spearman correlation coefficient analysis. In addition, the overall survival (OS) and progression-free survival (PFS) rates among PD-L1 inhibitor managed sufferers were acquired through a follow-up visit. Finally, we used a group of assays, including 5-bromo-2'-dexoyuridine (BrdU) and colony formation test, wound healing experiment, flow cytometry, and nude mice xenograft experiment, to explore the functions of circulating exosomal miR-16-5p on LUAD cell proliferation, apoptosis, and migration, as well as tumor development, respectively. RESULTS: PD-L1 expression was positively related to T stage (tumor size stage), and PD-L1 inhibitor treatment reduced the PD-L1 expression and mitigated T stage in PD-L1-positive LUAD sufferers. For PD-L1-positive LUAD sufferers, elevated PD-L1 expression or reduced serum exosomal miR-16-5p level were linked to longer PFS and OS upon PD-L1 inhibitor treatment. The number of exosomes in patient's serum was more than that in the serum of healthy individuals, and PD-L1 inhibitor treatment decreased the number of serum-derived exosomes in PD-L1-positive LUAD sufferers. Exosome-derived miR-16-5p was downregulated in patient's serum and cell culture medium, and this was negatively linked to tumor stage and PD-L1 expression. Meanwhile, PD-L1 inhibitor treatment could increase the serum exosomal miR-16-5p expression, and the expression change of serum exosomal miR-16-5p was diametrically related to PD-L1 after the treatment. Moreover, the overexpression of PD-L1 accelerated tumor growth and decreased the exosomal miR-16-5p content in cell culture media, while exosomal miR-16-5p overexpression in cell culture media inhibited tumor development by decreasing the PD-L1 expression. Exosomal miR-16-5p overexpression in cell culture media also depressed LUAD cell proliferation and migration, and stimulated cell apoptosis, especially in the cells which cultured in the mediums with PD-L1 inhibitor in vitro. CONCLUSIONS: Serum exosomal miR-16-5p may be a latent tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in LUAD by regulating the PD-L1 expression.