Correlation between PD-L1 expression status and efficacy of immunotherapy as second-line or later-line therapy in advanced non-small cell lung cancer patients.

OBJECTIVE: The objective of this study is to evaluate the correlation between tumor proportionality scores (TPS) and the effectiveness of immune checkpoint inhibitors (ICIs) as the second or subsequent line therapies for individuals who received diagnoses of advanced non-small cell lung cancer (NSCLC). METHODS: The retrospective analysis was conducted on the medical records of a total of 143 patients who received diagnoses of stage IIIB/IV NSCLC and were admitted to our hospital from the beginning of 2019 to the end of September 2022. The follow-up period ended on 01 January 2023. The study used Kaplan-Meier survival curves to assess the progression-free survival (PFS) and overall survival (OS) of patients. Univariate and multivariate Cox proportional risk models were used to analyze the factors associated with the PFS and OS of advanced-stage NSCLC patients who received ICIs as the second or subsequent lines. RESULTS: Patients diagnosed with NSCLC who had a TPS ≥1% and got treatment with ICIs exhibit notably elevated rates of partial response, objective response rate, disease control rate and extended PFS in comparison to NSCLC patients with a TPS of <1% (P < 0.05). NSCLC patients with TPS within 1-49% [hazard ratio (HR) = 0.372; 95% confidence interval (CI), 0.140-0.993; P = 0.048] or ≥50% (HR = 0.276; 95% CI, 0.095-0.796; P = 0.017) were significantly associated with prolonged PFS, which were conducted by multivariate Cox regression analysis. CONCLUSION: Programmed death protein-1 expression status may be predictive markers of the effectiveness of ICIs as the second or subsequent lines of therapies in advanced NSCLC are influenced by TPS.

Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma.

OBJECTIVE: To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed. METHODS: First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed. RESULTS: Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression. CONCLUSION: This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.

Interleukin-17 levels correlate with poor prognosis and vascular endothelial growth factor concentration in the serum of patients with non-small cell lung cancer.

OBJECTIVE: The aim of this study was to explore the clinical role of serum interleukin-17 in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHOD: IL-17 expression and microvessel density (MVD) were measured via immunohistochemistry in 58 NSCLC tissues. Serum IL-17 and VEGF levels in NSCLC patients (n = 43) and healthy controls (n = 37) were analyzed via enzyme-linked immunosorbent assay. RESULTS: Serum IL-17 was elevated and the levels positively correlated with VEGF concentration in NSCLC patients. Multivariate analyses revealed that serum IL-17 levels were an independent prognostic factor in NSCLC. CONCLUSION: IL-17 may play a role in NSCLC progression by promoting angiogenesis.

Newly identified biomarkers for detecting circulating tumor cells in lung adenocarcinoma.

Circulating tumor cells (CTCs) have been implicated in cancer prognosis and follow up. Detection of CTCs was considered significant in cancer evaluation. However, due to the heterogeneity and rareness of CTCs, detecting them with a single maker is usually challenged with low specificity and sensitivity. Previous studies concerning CTCs detection in lung cancer mainly focused on non-small cell lung carcinoma. Currently, there is no report yet describing the CTC detection with multiple markers in lung adenocarcinoma. In this study, by employing quantitative real-time PCR, we identified four candidate genes (mRNA) that were significantly elevated in peripheral blood mononuclear cells and biopsy tissue samples from patients with lung adenocarcinoma: cytokeratin 7 (CK7), Ca(2+)-activated chloride channel-2 (CLCA2), hyaluronan-mediated motility receptor (HMMR), and human telomerase catalytic subunit (hTERT). Then, the four markers were used for CTC detection; namely, positive detection was defined if at least one of the four markers was elevated. The positive CTC detection rate was 74.0% in patients with lung adenocarcinoma while 2.2% for healthy controls, 6.3% for benign lung disease, and 48.0% for non-adenocarcinoma non-small cell lung carcinoma. Furthermore, in a three-year follow-up study, patients with an increase in the detection markers of CTCs (CK7, CLCA2, HMMR or hTERT) on day 90 after first detection had shorter survival time compared to those with a decrease. These results demonstrate that the combination of the four markers with specificity and sensitivity is of great value in lung adenocarcinoma prognosis and follow up.

Combination of four gene markers to detect circulating tumor cells in the peripheral blood of patients with advanced lung adenocarcinoma using real-time PCR.

The aim of this study was to establish a robust and reliable assay for the detection of circulating tumor cells (CTCs) in the peripheral blood (PB) of patients with advanced lung adenocarcinoma. We used real-time reverse transcription PCR (RT-PCR) to detect survivin, human telomerase reverse transcriptase (hTERT), cytokeratin-7 (CK-7) and thyroid transcription factor 1 (TTF-1) mRNA expression levels in 68 advanced lung adenocarcinoma patients and 30 healthy patients. Statistical analyses were additionally performed to examine the correlation between the mRNA expression levels of these markers with the clinicopathological features of advanced lung adenocarcinoma patients. The sensitivity of these four mRNA markers in the PB of advanced lung adenocarcinoma patients was 41.18, 61.76, 41.18 and 35.29%, respectively. The sensitivity of these four markers combined was 82.35%, which was significantly higher compared with single marker detection. Statistical analysis demonstrated that high expression levels of survivin, hTERT and TTF-1 mRNA are positively correlated with lymph node classification, and high expression levels of survivin, hTERT, CK7 and TTF-1 mRNA are positively correlated with distant metastasis (P<0.05). In addition, overexpression of these four mRNA markers is positively correlated with disease progression (P<0.05). Our data suggest that the combination of survivin, hTERT, CK-7 and TTF-1 mRNA markers may provide a valuable tool for CTC detection and is associated with disease progression in advanced lung adenocarcinoma patients.