Solitary Pulmonary Lesion in Patients with History of Malignancy: Primary Lung Cancer or Metastatic Cancer?

BACKGROUND: Defining the status of solitary pulmonary lesion (SPL) in patients with history of malignancy is important because primary lung cancer (PLC) or intrapulmonary metastasis might indicate different surgical strategies. The aim of this study is to identify factors related to the status of these lesions and construct a clinical model to estimate the pretest probability of PLC. METHODS: From January 2005 to January 2016, 104 patients with previous malignancy and suitable for surgery were retrospectively studied. Univariate and multivariate analyses were performed to identify possible factors related to SPLs. A nomogram was constructed to differentiate PLC from intrapulmonary metastasis. RESULTS: Ninety-seven (93.3%) patients were diagnosed as malignant postoperatively, including 61 patients with intrapulmonary metastasis and 36 patients with PLC. Multivariate analysis showed that site of primary tumor [head and neck squamous cell cancer: odds ratio (OR) = 28.509, P = 0.006; genitourinary cancer: OR = 23.928, P = 0.012], negative lymph node status of primary tumor (OR = 3.154, P = 0.038), spiculation of SPL (OR = 3.972, P = 0.022), and central location of SPL (OR = 4.679, P = 0.026) were four independent factors differentiating PLC from intrapulmonary metastasis. All of these were included in the nomogram. The C-index of the nomogram for predicting probability was 0.82. CONCLUSIONS: Incidence of malignant SPLs was fairly high in patients with history of malignancy. A nomogram including site and lymph node status of primary tumor, and spiculation and location of SPL might be a good tool for differentiating PLC from intrapulmonary metastasis preoperatively and guiding treatment.

[Retracted] MicroRNA­19a­3p inhibits the cellular proliferation and invasion of non­small cell lung cancer by downregulating UBAP2L.

[This retracts the article DOI: 10.3892/etm.2020.8926.].

MicroRNA-19a-3p inhibits the cellular proliferation and invasion of non-small cell lung cancer by downregulating UBAP2L.

MicroRNAs (miRNAs) are increasingly recognized as important regulators of non-small cell lung cancer (NSCLC) progression by directly regulating their target genes. The aim of the present study was to assess the biological role of miR-19a-3p in NSCLC. It was revealed that miR-19a-3p expression was significantly downregulated in human NSCLC tissues and cell lines compared with normal tissues and lung epithelial cells. In addition, a lower miR-19a-3p expression was significantly associated with Tumor Node Metastasis stage and lymph node metastasis. Furthermore, the upregulation of miR-19a-3p in NSCLC cell lines significantly inhibited cell proliferation, migration and invasion, as determined using an MTT, colony formation, wound healing and transwell Matrigel invasion assays, respectively. A luciferase reporter assay and western blotting determined that ubiquitin associated protein 2 like (UBAP2L) was a direct target of miR-19a-3p and could be inhibited through the upregulation of miR-19a-3p in NSCLC. In addition, UBAP2L silencing induced similar effects to those observed following miR-19a-3p overexpression. The overexpression of UBAP2L partially reversed the effects of miR-19a-3p on NSCLC cell lines. Collectively, these data indicated that miR-19a-3p may serve as a tumor suppressor partly through the regulation of UBAP2L expression in NSCLC and that the targeting of miR-19a-3p may be a novel method for NSCLC treatment.

MiR-520b restrains cell growth by targeting HDAC4 in lung cancer.

BACKGROUND: MicroRNAs (miRNAs) function as tumor promoting or tumor suppressing factors in many cancers. MiR-520b contributes to progression in head-neck and liver cancers, spinal osteosarcoma, and glioma; however, the association of miR-520b with lung cancer progression remains unknown. In this investigation, we explore the effect of miR-520b targeting HDAC4 on lung cancer growth. METHODS: The regulation of miR-520b or its inhibitor on HDAC4 expression was analyzed using Western blot analysis. After treatment of miR-520b or its inhibitor, miR-520b and HDAC4 levels were examined using quantitative real time-PCR. The modulation of miR-520b on HDAC4 was investigated by luciferase reporter gene assay. Cell proliferation evaluation was performed using colony formation and methyl-thiazolyl-tetrazolium assays. The correlation between miR-520b and HDAC4 in human clinical samples was verified using Pearson's correlation coefficient. RESULTS: An obvious decrease in HDAC4 expression was observed in lung cancer A549 cells treated with different doses of miR-520b. The miR-520b inhibitor enhanced HDAC4 expression in lung cancer cells. Bioinformatics predicted the targeting of miR-520b on HDAC4. MiR-520b directly targeted the 3' untranslated region of HDAC4. The introduction of miR-520b obviously inhibited cell proliferation in vitro. Anti-miR-520b was capable of accelerating lung cancer cell proliferation; however, HDAC4 knockdown destroyed anti-miR-520b-induced cell proliferation. Finally, a negative correlation between miR-520b and HDAC4 was observed in clinical human lung cancer samples. CONCLUSION: MiR-520b decreases HDAC4 expression to control cell proliferation in lung cancer.

[Applicable Value of AMSS-PCR in Lung Cancer Gene Mutation Detection].

BACKGROUND: The detection of driver oncogenes of lung cancer is of great importance. There are various gene detection techniques nowadays which are different from each other. We carried out this study to investigate the specificity and sensitivity of assay panels based on an Amplification Refractory Mutation System-polymerase chain reaction (ARMS-PCR) technique of Amplification Mutation Specific System (AMSS) in detection of lung cancer gene mutation. To estimate the applicable value of assay panels in clinical settings. METHODS: We collected cancer tissue specimens or fluid specimens from 309 patients. Mutation results were presented for those samples previously detected by ARMS-PCR. In comparison, we carried out AMSS-PCR using (epidermal growth factor receptor, EGFR) assay panel and Six-Alliance assay panel as well as Sanger sequencing. Software SPSS 22.0 (SPSS IBM) was used for statistical analysis. RESULTS: The rates of consistency between the results by assay panels and Sanger sequencing or ARMS-PCR were 97.41% and 97.73%, respectively. Besides, EGFR assay panel had higher consistency rates with other detection methods than Six-Alliance assay panel. As for consistency test, the Kappa values of assay panels with Sanger sequencing, assay panels with ARMS-PCR, and ARMS-PCR with Sanger sequencing were 0.946, 0.953, and 0.913, respectively. The receiver operating characteristic curve (ROC) area under curve (AUC) of assay panels was 0.976 referring to Sanger sequencing, and 0.975 as ARMS-PCR was referred to. CONCLUSIONS: AMSS-PCR can make an optimal cancer gene mutation detection method for clinical settings.