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Lung cancer is the malignant tumor with the highest mortality rate in the world. Heterogeneity of lung cancer, usually studied by sequencing technology, is considered to have important clinical significance in current studies. However, general sequencing technology can only explain the differences between samples integrally and its resolution is not enough to describe the differences between the individual cells. Therefore, people urgently hope to understand the cell type, state, subgroup distribution in the tumor microenvironment and the communication behavior between cells in the single cell level. Single-cell sequencing technology solves this problem. Using this technique will contribute to further understanding the mechanism of the occurrence and development of lung cancer, discovering new diagnostic markers and therapeutic targets, and providing theoretical references for the precise treatment of lung cancer patients in the future. This article reviews the progress of single-cell sequencing technology and focuses on its research on lung cancer tumor heterogeneity, tumor microenvironment, invasion and metastasis, treatment response, and drug resistance. .
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BACKGROUND@#Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers.@*METHODS@#Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis.@*RESULTS@#The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006).@*CONCLUSIONS@#In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.
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Objective To investigate the expression of Fascin in early-stage NSCLC, evaluate the relevance between Fascin expression level and prognosis.Methods The immunohistochemistry method was used to assess the expression of Fas-cin in 111 lung cancer FFPE tissues with stage Ⅰ and Ⅱ NSCLC.The relationship between Fascin expression and the clinico-pathological characteristics was analyzed.The prognostic significance of Fascin expression was evaluated with Kaplan-Meier sur-vival analysis.Results In the early-stage of NSCLC, the positive rate of Fascin expression was 64.8%, no expression in the paracarcinoma tissue.The positive rate of squamous cell carcinoma was 78.7% and was significantly higher than that in adeno-carcinoma 48.0%(P<0.01).Whether in squamous cell carcinoma or adenocarcinoma group, the expression of Fascin was correlated significantly with lymph node metastasis tumor stages and DFS(P<0.05).And the positive expression of Fascin was an independent risk factor of poor prognosis for patient with NSCLC .Conclusion Fascin is expected to be a biomarker for the prognosis of patients with early-stage NSCLC.
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<p><b>OBJECTIVE</b>The aim of this study was to detect the plasma concentration of OLC1 (overexpressed in lung cancer 1) protein as a potential cancer biomarker, and evaluating its clinical application value in the diagnosis of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>We prepared OLC1 antibody with OLC1 full length protein, in 5-6-week old Bal B/c mice. Each mouse was immunized four times at a dose of 15-30 µg antigen protein, and the interval between two consecutive immunizations was two weeks. Antibody screening was made by ELISA and Western blot, and a double antibody sandwich ELISA kit was developed. We used this established ELISA kit to detect the plasma concentration of OLC1 protein in 281 NSCLC patients and 92 gender- and age-matched healthy controls. Area under the receiver operating characteristic curve (AUC) was used to evaluate the detection efficacy of OLC1.</p><p><b>RESULTS</b>We obtained 11 OLC1 monoclonal antibodies and successfully established the ELISA kit to detect the plasma concentration of OLC1 with a detection range from 1.95 ng/ml to 62.50 ng/ml. OLC1 concentration in the case group (124.69 ng/ml) was significantly higher than that in the control group (67.07 ng/ml, P < 0.001). In the scenario of distinguishing NSCLC from control group, AUC result was 0.69. When the cut-off was set at 67.72 ng/ml, the sensitivity and specificity was 84.4% and 51.1%, respectively. In term of distinguishing early lung cancer (IA) from normal controls, the AUC, sensitivity and specificity were 0.68, 77.8% and 54.4%, respectively.</p><p><b>CONCLUSION</b>The plasma concentration of OLC1 protein is significantly elevated in NSCLC patients. OLC1 may be as a potential cancer biomarker applied in clinical diagnosis.</p>