Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.

OBJECTIVE: Lung adenocarcinoma (LA) is one of the most common malignancies and is responsible for the greatest number of tumor-related deaths. Our research aimed to explore the molecular subtype signatures of LA to clarify the correlation among the immune microenvironment, clinical outcomes, and therapeutic response. METHODS: The LA immune cell marker genes (LICMGs) identified by single-cell RNA sequencing (scRNA-seq) analysis were used to discriminate the molecular subtypes and homologous immune and metabolic traits of GSE72094 LA cases. In addition, the model-building genes were identified from 1441 LICMGs by Cox-regression analysis, and a LA immune difference score (LIDscore) was developed to quantify individual differences in each patient, thereby predicting prognosis and susceptibility to immunotherapy and chemotherapy of LA patients. RESULTS: Patients of the GSE72094 cohort were divided into two distinct molecular subtypes based on LICMGs: immune activating subtype (Cluster-C1) and metabolically activating subtype (cluster-C2). The two molecular subtypes have distinct characteristics regarding prognosis, clinicopathology, genomics, immune microenvironment, and response to immunotherapy. Among the LICMGs, LGR4, GOLM1, CYP24A1, SFTPB, COL1A1, HLA-DQA1, MS4A7, PPARG, and IL7R were enrolled to construct a LIDscore model. Low-LIDscore patients had a higher survival rate due to abundant immune cell infiltration, activated immunity, and lower genetic variation, but probably the higher levels of Treg cells in the immune microenvironment lead to immune cell dysfunction and promote tumor immune escape, thus decreasing the responsiveness to immunotherapy compared with that of the high-LIDscore patients. Overall, high-LIDscore patients had a higher responsiveness to immunotherapy and a higher sensitivity to chemotherapy than the low-LIDscore group. CONCLUSIONS: Molecular subtypes based on LICMGs provided a promising strategy for predicting patient prognosis, biological characteristics, and immune microenvironment features. In addition, they helped identify the patients most likely to benefit from immunotherapy and chemotherapy.

Regulation of circular RNAs act as ceRNA in a hypoxic pulmonary hypertension rat model.

To explore potential critical genes and identify circular RNAs (circRNAs) that act as the competitive endogenous RNA (ceRNA) in a hypoxic pulmonary hypertension (HPH) rat model. Constructed rat model, and a bioinformatics method was used to analyse differentially expressed (DE) genes and construct a circRNA-miRNA-mRNA ceRNA regulatory network. Then, qRT-PCR was used to verify. The significant DEcircRNAs/DEmiRNAs/DEmRNAs was showed, and a ceRNA network with 8 DEcircRNAs, 9 DEmiRNAs and 46 DEmRNAs were constructed. The functional enrichment suggested the inflammatory response, NF-κB signalling, MAPK cascade and Toll-like receptor were associated with HPH. Further assessment confirmed that circ_002723, circ_008021, circ_016925 and circ_020581 could have a potential ceRNA mechanism by sponging miR-23a or miR-21 to control downstream target gene and be involved in the pathophysiology of HPH. The qRT-PCR validation results were consistent with the RNA-Seq results. This study revealed potentially important genes, pathways and ceRNA regulatory networks in HPH.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

[Expression of transcription factor SOX4 and its clinical significance in female lung cancer patients in Xuanwei area, Yunnan Province].

OBJECTIVE: To investigate the expression of transcription factor SOX4 in lung cancer tissues of female patients in Xuanwei area, Yunnan Province, and explore its correlation with clinicopathological characteristics and prognosis of the female patients. METHODS: Real-time PCR was applied on lung cancer specimens and their corresponding normal lung tissues from 96 female cases of Xuanwei area to assess the expression of SOX4 mRNA. Immunohistochemical staining was performed to investigate the SOX4 protein expression, and further to elucidate its correlation with clinicopathological characteristics and prognosis. RESULTS: The expression level of SOX4 mRNA in the cancer tissues (2.53 ± 1.65) was significantly higher than that of matched normal tissues (1.43 ± 1.14, P = 0.003). Immunohistochemical staining showed that there were 53.1% (51/96) positive expression of SOX4 protein in the cancer tissue and only 26.0% (25/96) in matched normal tissue (P < 0.001). The expression of SOX4 protein had a significant correlation with clinical stage, lymph node metastasis and differentiation of tumor (P < 0.05). The survival analysis by Kaplan-Meier method showed that patients with positive expression of SOX4 protein, lymph node metastasis and advanced tumor stage had a significantly shorter median survival time (P < 0.05). Cox regression survival analysis showed that pathological grade was a significant independent factor affecting prognosis. CONCLUSIONS: The expressions of SOX4 mRNA and protein are significantly up-regulated in Xuanwei female lung cancer patients. Patients with positive SOX4 expression have a shorter median survival time. SOX4 protein expression level combined with pathological grade can be used as a prognostic indicator of female lung cancer patients in Xuanwei area, Yunnan Province.

[Relationship between high incidence of lung cancer among non-smoking women and silica in C1 bituminous coal in Xuanwei, Yunnan Province, China].

OBJECTIVE: To measure the content of silica in C1 bituminous coal and its combustion products in the high-incidence area of lung cancer in Xuanwei, Yunnan Province, China and to investigate the relationship between high incidence of lung cancer among non-smoking women and silica produced naturally in C1 bituminous coal in Xuan Wei. METHODS: The C1 bituminous coal widely used in the high-incidence area of lung cancer in Xuanwei was selected as experiment group, while the C2+1, K7, and M30 bituminous coal that was mined and used in the low-incidence area of lung cancer in Xuanwei for more than 10 years were selected as control group. Fourteen paraffin-embedded cancer tissue samples from the non-smoking women with non-small cell lung cancer who were born in Xuanwei and were at least the 3rd generation of the family living there were collected from the department of pathology, the third affiliated hospital of kunming medical university (tumor hospital of yunnan province). Titrimetric potassium silicofluoride method was used to measure the content of silica in raw coal and its bottom ashes in 20 samples from the experimental group and control group. Scanning electron microscopy (SEM) was used to observe the morphology of silica particles in C1 bituminous coal and its bottom ashes, and scanning electron microscopy coupled with energy dispersive X-ray analyzer (SEM-EDX) was used to analyze the microscopic composition. Transmission electron microscope (TEM) was used to observe the morphology of silica particles in the bottom ashes and coal soot of C1 bituminous coal as well as the lung cancer tissue from the non-smoking women in Xuanwei, and transmission electron microscope coupled with energy dispersive X-ray analyzer (TEM-EDX) was used to analyze the microscopic composition. The silica particles were separated from the coal soot and bottom ashes and characterized by physical method. RESULTS: The silica content in C1 bituminous coal and its bottom ashes was significantly higher than that in C2+1, K7, and M30 bituminous coal (P < 0.05). The bottom ashes of C1 bituminous coal contained a large quantity of silica particles, mostly with microscale sizes. Silica particles were found in the soot of C1 bituminous coal and the lung cancer tissue from non-smoking women in Xuanwei. The silica particles in the bottom ashes were mostly 120 ∼ 500 nm in diameter, had various shapes, and contained such elements as iron, aluminium, calcium, and potassium; the silica particles in the coal soot were mostly nanoscale, ranging from 37 nm to 80 nm in diameter, had various shapes, with some in fibrous form, had non smooth surfaces, and contained such elements as iron, potassium, calcium, aluminium, and sulfur. CONCLUSION: In Xuanwei, the incidence of lung cancer among non-smoking women is high in the area where silica-rich C1 bituminous coal is produced. There are silica particles enriched in both the combustion products (coal soot and bottom ashes) of C1 bituminous coal and the cancer tissue from the non-smoking women with non-small cell lung cancer, with similar morphology and microscopic composition. We hypothesize that the silica particles from combusted C1 bituminous coal in Xuanwei are mixed with indoor air and inhaled along with other suspended particles.

Fibrinogen-to-albumin ratio predicts overall survival of hepatocellular carcinoma.

BACKGROUND: Fibrinogen-to-albumin ratio (FAR) has been found to be of prognostic significance for several types of malignant tumors. However, less is known about the association between FAR and survival outcomes in hepatocellular carcinoma (HCC) patients. AIM: To explore the association between FAR and prognosis and survival in patients with HCC. METHODS: A total of 366 histologically confirmed HCC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant data were extracted from the hospital information system. The optimal cutoff for baseline serum FAR measured upon disease diagnosis was established using the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional hazards models were used to determine the crude and adjusted associations between FAR and the overall survival (OS) of the HCC patients while controlling for various covariates. The restricted cubic spline (RCS) was applied to estimate the dose-response trend in the FAR-OS association. RESULTS: The optimal cutoff value for baseline FAR determined by the ROC was 0.081. Multivariate Cox proportional hazards model revealed that a lower baseline serum FAR level was associated with an adjusted hazard ratio of 2.43 (95% confidence interval: 1.87-3.15) in the OS of HCC patients, with identifiable dose-response trend in the RCS. Subgroup analysis showed that this FAR-OS association was more prominent in HCC patients with a lower baseline serum aspartate aminotransferase or carbohydrate antigen 125 level. CONCLUSION: Serum FAR is a prominent prognostic indicator for HCC. Intervention measures aimed at reducing FAR might result in survival benefit for HCC patients.

Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer.

CACNA1E is a gene encoding the ion-conducting α1 subunit of R-type voltage-dependent calcium channels, whose roles in tumorigenesis remain to be determined. We previously showed that CACNA1E was significantly mutated in patients with non-small cell lung cancer (NSCLC) who were long-term exposed to household air pollution, with a mutation rate of 19% (15 of 79 cases). Here we showed that CACNA1E was also mutated in 207 (12.8%) of the 1616 patients with NSCLC in The Cancer Genome Atlas (TCGA) datasets. At mRNA and protein levels, CACNA1E was elevated in tumor tissues compared to counterpart non-tumoral lung tissues in NSCLCs of the public datasets and our settings, and its expression level was inversely associated with clinical outcome of the patients. Overexpression of wild type (WT) or A275S or R249G mutant CACNA1E transcripts promoted NSCLC cell proliferation with activation of epidermal growth factor receptor (EGFR) signaling pathway, whereas knockdown of this gene exerted inhibitory effects on NSCLC cells in vitro and in vivo. CACNA1E increased current density and Ca2+ entrance, whereas calcium channel blockers inhibited NSCLC cell proliferation. These data indicate that CACNA1E is required for NSCLC cell proliferation, and blockade of this oncoprotein may have therapeutic potentials for this deadly disease.

[Effects of enalapril on NF-kappaB expression in mucus hypersecretion rats induced by acrolein exposure].

OBJECTIVE: To investigate the effects of enalapril on nuclear factor-kappa B (NF-kappaB) expression in a rat model of mucus hypersecretion induced by acrolein. METHODS: The rat model of mucus hypersecretion was established by the inhalation of acrolein. Then the mucus hypersecretion rats were treated by enalapril. The AB/PAS stain was performed to measure the secretion of airway in the rats, while the mRNA and protein expression levels of NF-kappaB in the airway were detected by RT-PCR, ISH, immunohistochemistry and Western blot. RESULTS: With the inhalation of acrolein, the airway secretion increased obviously, while the mRNA and protein expressions of NF-kappaB in lung were increased. The treatment of enalapril resulted in a significant decrease of airway secretion, as well as the downregulation of NF-kappaB in both protein and gene level. CONCLUSION: Enalapril (ACE inhibitor) treatment could effectively decrease pulmonary mucus hypersecretion in acrolein-treated rats, which may be related to the downregulation of NF-kappaB expression.

[Changes of proteomics in the lung of rats subjected to acrolein inhalation after enalapril administration].

OBJECTIVE: To study the molecular mechanism of enalapril on rat chronic bronchopneumonia model with proteomics method. METHODS: Enalapril treatment applied to the recovery of chronic bronchopneumonia in rats, after enalapril administration, two-dimensional electrophoresis and mass spectrometry were performed to analyze the difference of the peptide finger print map and amino acid sequence of rat lung tissues in acrolein inhalation group and enalapril treatment group. RESULTS: Three differential protein spots from average 545 protein spots were found in lung tissues of two groups. These protein spots were identified as glyceraldehyde-3-phosphate dehydrogenase, T-kininogen 1 precursor and dihydropyrimidinase-like 2 with mass spectrometry. The significant upregulation in the level of dihydropyrimidinase-like 2, downregulation of glyceraldehyde-3-phosphate dehydrogenase, and the lose of T-kininogen 1 precursor in enalapril treatment group were observed. CONCLUSION: The expression difference in three proteins might contribute to the preventive role of enalapril on acrolein inhalation induced rat chronic bronchopneumonia.

Connexins and cAMP Cross-Talk in Cancer Progression and Metastasis.

Connexin-containing gap junctions mediate the direct exchange of small molecules between cells, thus promoting cell-cell communication. Connexins (Cxs) have been widely studied as key tumor-suppressors. However, certain Cx subtypes, such as Cx43 and Cx26, are overexpressed in metastatic tumor lesions. Cyclic adenosine monophosphate (cAMP) signaling regulates Cx expression and function via transcriptional control and phosphorylation. cAMP also passes through gap junction channels between adjacent cells, regulating cell cycle progression, particularly in cancer cell populations. Low levels of cAMP are sufficient to activate key effectors. The present review evaluates the mechanisms underlying Cx regulation by cAMP signaling and the role of gap junctions in cancer progression and metastasis. A deeper understanding of these processes might facilitate the development of novel anticancer drugs.

Connexins in Lung Cancer and Brain Metastasis.

Connexins (Cxs) are involved in the brain metastasis of lung cancer cells. Thus, it is necessary to determine whether gap junction-forming Cxs are involved in the communication between lung cancer cells and the host cells, such as endothelial cells, forming the brain-blood-barrier, and cells in the central nervous system. Data from multiple studies support that Cxs function as tumor suppressors during lung cancer occurrence. However, recent evidence suggests that during metastasis to the brain, cancer cells establish communication with the host. This review discusses junctional or non-junctional hemichannel studies in lung cancer development and brain metastasis, highlighting important unanswered questions and controversies.

The influences of TGF-ß1 upon the human adenocarcinoma cell of lung A549 and cellular immunity.

BACKGROUND: The cellular immunity of lung cancer patients is mainly the immune response of T cells, which plays an important role in tumour cell killing and immune surveillance. Transforming growth factor 1 (TGF-ß1) is secreted by tumour cells that can suppress the immune response and is an important group of immune down-regulation factors. Our study aims to investigate the effect of TGF-ß1 on the morphology and cellular immune function of A549 and peripheral blood mononuclear cells (PBMCs). METHODS: A549 cell line was cultured, PBMCs were cultured with different concentrations of TGF-ß1, and the morphology of A549 cells and PBMCs were seen. The levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and TNF and the numbers of CD3, CD4, CD8, CD4/CD8, and CD3 CD25 and CD4 CD25 in PBMCs were detected. RESULTS: During co-culture of A549 with PBMCs, TGF-ß1 can induced A549 showing epithelial-to-mesenchymal transition, enhanced its ability of migration and infiltration. Simultaneously, TGF-ß1 can depressing the growth and proliferation of PBMCs, inhibiting T-cell activation, and accelerating the PBMCs apoptosis. TGF-ß1 can inhibits A549 Th1 related-cytokines, enhance Th2 related-cytokines, cause the disorder of Th1/Th2, resulting in the Th1 cellular dominate immunity decline. CONCLUSIONS: TGF-ß1 may affect the secretion of related cytokines, hinder the activation of T lymphocytes, destroy the immune surveillance and killing effect of the body, and thus inhibit the cellular immunity.

Suppression of Musashi­2 by the small compound largazole exerts inhibitory effects on malignant cells.

RNA­binding protein Musashi­2 (MSI2) serves as a regulator of numerous pivotal biological processes associated with cancer initiation, development and resistance to treatment, and may represent a promising drug target. However, whether MSI2 inhibition is of value in antitumor treatment remains to be determined. The present study demonstrated that MSI2 was upregulated in non­small cell lung cancer (NSCLC) and was inversely associated with the clinical outcome of the patients. Molecular docking analysis demonstrated that the small compound largazole binds to and may be a potential inhibitor of MSI2. Largazole markedly decreased the protein and mRNA levels of MSI2 and suppressed its downstream mammalian target of rapamycin signaling pathway. Largazole also inhibited the proliferation and induced apoptosis of NSCLC and chronic myeloid leukemia (CML) cells (including bone marrow mononuclear cells harvested from CML patients). These results indicate that MSI2 is an emerging therapeutic target for NSCLC and CML, and the MSI2 inhibitor largazole may hold promise as a treatment for these malignancies.

Systematic identification of CDC34 that functions to stabilize EGFR and promote lung carcinogenesis.

BACKGROUND: How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified. METHODS: A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated in vitro and in vivo. FINDINGS: We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation in vitro and in vivo. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation. INTERPRETATION: These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.

[Determination of thirty three elements in lung cancer tissues of patients with lung cancer by microwave digestion-ICP-MS].

A method for determining 33 elements in lung tissues of patients with lung cancer was developed by using vacuum freeze-drying microwave digestion-ICP-MS. The lung tissue samples were treated by vacuum freeze-drying equipment. After microwave digestion in HNO3-H2O2 solution system, the samples were diluted with the method of constant volume. Under the optimized conditions the samples were analyzed by ICP-MS. The double internal standard elements Rh and Re were used to compensate for matrix suppression effect and sensitivity drift. The analytical results showed that the detection limits of the 33 elements were 0.01-0.45 ng x mL(-1). The national standard reference material GBW(E)080193 bovine liver was analyzed by the described method and the measured element values accorded with the standard values or the reference values. The relative standard deviation (RSD) of the method was 2.1%-14.3%. The recovery rates of the studied elements were 90.1%-117.5%. The contents of 33 elements in lung cancer tissues, paracancerous lung tissues and benign lung tissues of 6 patients with lung cancer were determined by the method. It was indicated that the method is rapid, simple and accurate for determining multi-elements in human lung tissue and other biological samples.

Systematic analysis of concentrations of 52 elements in tumor and counterpart normal tissues of patients with non-small cell lung cancer.

BACKGROUND: Many studies have documented the abnormal concentrations of major/trace elements in serum or malignant tissues of patients, but very few works systematically tested the concentrations of elements in tumor tissues in comparison with paired adjacent normal tissues from the same patients. METHODS: Tumor and adjacent normal lung tissues were obtained from 93 patients with previously untreated NSCLC, and 43 patients whose tumor and paired normal lung tissues reached 200 mg or more were selected for measurement of the elements' concentrations using an inductively coupled plasma-atomic emission spectrometer. RESULTS: We found that the concentrations of the 52 elements varied from 0.4 ng/g tissue (Lu, Pd, and Tm) to 1 658 000 ng/g (Na), 1 951 000 ng/g (P), and 2 495 000 ng/g (K). Thirty eight of the 52 (73.1%) elements showed approximately equal concentrations in tumor and adjacent normal lung tissues of the patients. The concentrations of nine elements (K, P, Mg, Zn, Rb, Cu, Se, Cs, and Tl) in tumor samples were significantly higher than their paired normal lung tissues, and five elements (Na, Fe, Cr, Cd, and Ge) exhibited decreased concentrations in cancer samples compared to counterpart normal lung tissues. Low Fe in tumor samples was associated with smoking history, whereas low Cr was associated with histology (squamous cell carcinoma) of the patients. CONCLUSIONS: Our results demonstrate that measurement of elements' concentrations in both cancer and paired normal tissues is important to get insights into the roles of these elements in carcinogenesis, and therapeutic approaches to normalize the elements are warranted to treat NSCLCs.

The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy.

Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on lung epithelial cells in vitro and in vivo, which is mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppresses BaP-induced lung cancer. In 37 patients treated with anti-PD-1 antibody pembrolizumab, 13/16 (81.3%) patients who achieve partial response or stable disease express high levels of AhR, whereas 12/16 (75%) patients with progression disease exhibit low levels of AhR in tumor tissues. AhR inhibitors exert significant antitumor activity and synergize with anti-PD-L1 antibody in lung cancer mouse models. These results demonstrate that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.

Lung cancer imaging methods in China from 2005 to 2014: A national, multicenter study.

BACKGROUND: The study was conducted to examine changes in diagnostic and staging imaging methods for lung cancer in China over a 10-year period and to determine the relationships between such changes and socioeconomic development. METHODS: This was a hospital-based, nationwide, multicenter retrospective study of primary lung cancer cases. The data were extracted from the 10-year primary lung cancer databases at eight tertiary hospitals from various geographic areas in China. The chi-squared test was used to assess the differences and the Cochran-Armitage trend test was used to estimate the trends of changes. RESULTS: A total of 7184 lung cancer cases were analyzed. Over the 10-year period, the utilization ratio of diagnostic imaging methods, such as chest computed tomography (CT) and chest magnetic resonance imaging (MRI), increased from 65.79% to 81.42% and from 0.73% to 1.96%, respectively, while the utilization ratio of chest X-ray declined from 50.15% to 30.93%. Staging imaging methods, such as positron emission tomography-CT, neck ultrasound, brain MRI, bone scintigraphy, and bone MRI increased from 0.73% to 9.29%, 22.95% to 47.92%, 8.77% to 40.71%, 42.40% to 62.22%, and 0.88% to 4.65%, respectively; abdominal ultrasound declined from 83.33% to 59.9%. These trends were more notable in less developed areas than in areas with substantial economic development. CONCLUSION: Overall, chest CT was the most common radiological diagnostic method for lung cancer in China. Imaging methods for lung cancer tend to be used in a diverse, rational, and regionally balanced manner.

Clinical characteristics and medical service utilization of lung cancer in China, 2005-2014: Overall design and results from a multicenter retrospective epidemiologic survey.

OBJECTIVES: This study aimed to explore the clinical profile and its trajectory of lung cancer on clinicopathological characteristics and medical service utilization in China. METHODS: Patients diagnosed with primary lung cancer in tertiary hospitals during 2005-14 were selected from seven geographic regions of China. Data on clinical characteristics and medical service utilization was extracted from medical record, and the ten-year trends were explored. RESULTS: A total of 7184 patients were included, the mean age was 58.3 years and the male-to-female-ratio was 2.7. From 2005 to 2014, the proportion of ≥60 year-old patients increased from 41.2% to 56.2% (p < 0.001). The smoking rate decreased from 62.9% to 51.1% (p < 0.001) and the proportion of females increased from 23.5% to 31.9% (p < 0.001). The proportion of advanced stage increased from 41.9% to 47.4% (p < 0.001). Adenocarcinoma's proportion increased from 36.4% to 53.5% (p < 0.001) while that of squamous carcinoma decreased from 45.4% to 34.4% (p < 0.001). The application of chest X-ray dropped from 50.2% to 31.0% (p < 0.001) but that of chest CT increased from 65.8% to 81.4% (p < 0.001). As two main treatment options, chemotherapy (p = 0.290) and surgery (p = 0.497) remained stable. The medical expenditure per patient increased from 40,508 to 66,020 Chinese Yuan (p < 0.001). CONCLUSIONS: The sustaining high smoking exposure, increasing proportion of female patients, advancing clinical stage, shifting of predominant pathology and increasing medical expenditure demonstrate potential challenges and directions on lung cancer prevention and control in China. Despite substantial changes of clinical characteristics, main treatment options remained unchanged, which needs further investigation.

What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BACKGROUND: Most lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population. METHODS: We conducted a 10 years (2005-2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions. RESULTS: A total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477-3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721-0.989). The odds of having both symptoms and physical signs were higher in patients with late-stage disease than in those with early-stage disease (P < 0.0001). CONCLUSIONS: The symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.