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Background Solid pulmonary nodules are different from subsolid nodules and the diagnosis is much more challenging. We intended to evaluate the diagnostic and prognostic value of radiomics and deep learning technologies for solid pulmonary nodules. Methods Retrospectively enroll patients with pathologically-confirmed solid pulmonary nodules and collect clinical data. Obtain pre-treatment high-resolution thoracic CT and manually delineate the nodule in 3D. Then, all patients were randomly divided into training and testing sets at a ratio of 7:3, and convolutional neural networks (CNN) models and random forest (RF) models were established. Survival analyses were performed for patients with solid adenocarcinomas. Results Totally 720 solid pulmonary nodules were enrolled, 348 benign and 372 malignant. The CNN model with clinical features achieved the highest AUC [0.819, 95% confidence interval (CI): 0.760–0.877] with a sensitivity of 0.778, specificity of 0.788 and accuracy of 0.783. No significant differences were observed between the CNN and radiomics models. There were 295 solid adenocarcinomas in survival analysis. Different disease-free survival was observed between the low-risk and high-risk groups divided according to the radiomics Rad-score. However, the groups based on deep learning signatures showed similar survival. Cox regression analysis indicated that the radiomics Rad-score (hazard ratio: 5.08, 95% CI: 2.61–9.90) was an independent predictor of recurrence. Conclusions The radiomics and deep learning models can well predict the malignancy of solid pulmonary nodules. Radiomics signatures also demonstrate prognostic value in solid adenocarcinomas.

Primary pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare non-small cell lung cancer (NSCLC) subtype. Clinical features have been described in our previous report, but molecular characteristics remain unclear. Herein, pLELC genomic features were explored. Among 41,574 lung cancers, 128 pLELCs and 162 non-pLELC NSCLCs were enrolled. Programmed cell death ligand 1 (PD-L1) and protein 53 (p53) expression was detected in 47 surgically resected pLELC samples by immunohistochemical assays. Multiomics genomic analyses, including whole-genome sequencing (WGS), RNA whole-transcriptome sequencing (RNA-seq), and Epstein-Barr virus (EBV) integration analyses, were performed on eight frozen pLELC tissues and compared with 50 lung adenocarcinomas (LUADs) and 50 lung squamous cell carcinomas (LUSCs) from The Cancer Genome Atlas (TCGA) and another 26 EBV-positive nasopharynx cancers (EBV+-NPCs). Progression-free survival (PFS) and overall survival (OS) of pLELC patients were better than those of non-pLELC patients. High PD-L1 or p53 expression was associated with extended disease-free survival (DFS). pLELC had 14 frequently mutated genes (FMGs). Somatically mutated genes and enrichment of genetic lesions were found, which differed from observations in LUAD, LUSC, and EBV+-nasopharyngeal carcinoma (NPC). Three tumor-associated genes, zinc finger and BTB domain-containing 16 (ZBTB16), peroxisome proliferator activated receptor gamma (PPARG), and transforming growth factor beta receptor 2 (TGFBR2), were downregulated with copy number variation (CNV) loss. EBV was prone to integrating into intergenic and intronic regions with two upregulated miR-BamH1-A rightward transcripts (BARTs), BART5-3P and BART20-3P. Our findings reveal that pLELC has a distinct genomic signature. Three tumor-associated genes with CNV loss and two miR-BARTs might be involved in pLELC tumorigenesis.

The detection rate of the solitary pulmonary nodule (SPN) is increasing with the popularization of CT scanning. Malignancy risk stratification for SPN is a major clinical difficulty.There have been several guidelines for SPN assessment. Inconsistency of these guidelines makes the clinical application difficult and confusing.In this Rapid Recommendation, solid and subsolid SPNs are recommended to be evaluated respectively. Six factors, namely the combination of age with sex, smoking history, history of malignancy, family history of malignancy, and nodule size, are recommended for malignancy risk stratification for both kinds of SPNs; the border of nodules (spiculation and lobulation) is recommended for evaluating solid SPNs and the density of nodules (pure or mixed ground-glass nodule) is recommended for subsolid nodules. Among them, smoking history and radiologic features (nodule diameter, border, and density) are of relatively higher importance. A scoring system was proposed to assist malignancy risk stratification of SPNs, with a total score ranging from six points to 15 points (if solid) or 17 points (if subsolid). For each SPN, regardless of solid or subsolid in nature, a total score of ≤ 7 points suggested a low risk of being malignant, while 7 to 9 points suggested medium risk, and ≥ 9 points suggested high risk.This rapid recommendation was developed using the MAGIC (Making GRADE the Irresistible Choice) methodological framework. First, a clinical subcommittee identified the topic of recommendation and requested evidence. Then, an independent evidence synthesis subcommittee performed a comprehensive literature review and evaluated the evidence. Finally, based on findings from the systematic review and use of real-world data, the clinical subcommittee formulated recommendations, including the scoring system, through a consensus procedure.A total of 13857 patients with SPNs were included in the meta-analysis and the association between 12 candidate factors and the risk of SPNs being malignant was studied. Eventually, seven factors were recommended for SPNs evaluation, and a scoring system was proposed.The parameters included are objective. Therefore, this recommendation is feasible in clinical practice. However, there are several uncertainties, such as a lack of further verification. It might be misclassified by the scoring system. Clinicians could choose the most suitable scheme according to the recommendation, along with their own experience in specific situations.

To assess the association between prespecified factors and the malignancy risk of solitary pulmonary nodules (SPNs) to support the development of rapid recommendations for daily use in the Chinese setting.The expert panel for the rapid recommendations voted for 12 candidate factors based on published guidelines, selected publications, and clinical experiences. We then searched Medline, Embase, and Web of Science up to October 17, 2021, for studies investigating the association between these factors and the diagnosis of malignant SPNs in patients with CT-identified SPNs through multivariable regression analysis. The risk of bias was assessed using the Agency for Healthcare Research and Quality (AHRQ) Checklist. We pooled adjusted odds ratios (aOR) between candidate factors and the diagnosis of the malignant SPNs.A total of 32 cross-sectional studies were included. Nine factors were statistically associated with malignant SPNs: age (aOR 1.06, 95% confidence interval [CI]: 1.05-1.07), smoking history (2.83, 1.84-4.36), history of extrathoracic malignancy (5.66, 2.80-11.46), history of malignancy (4.64, 3.37-6.39), family history of malignancy (3.11, 1.66-5.83), nodule diameter (1.23, 1.17-1.31), spiculation (3.41, 2.64-4.41), lobulation (3.85, 2.47-6.01), and mixed ground-glass opacity (mGGO) density of the nodule (5.56, 2.47-12.52). No statistical association was found between family history of lung cancer, emphysema, nodule border, and malignant SPNs.Nine prespecified factors were associated with the concurrent malignancy risk among patients with SPNs. Risk stratification for SPNs is warranted in clinical practice.

Background The prognostic value of TP53 commutation in epidermal growth factor receptor (EGFR) mutant lung cancer is controversial and we therefore conducted this systematic review and meta-analysis. Methods A systematic search was carried out in Pubmed, Web of Science, the Cochrane Library, Medline and Embase up to 19 April 2018. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), the relative risk (RR) of objective response rate (ORR) were calculated. Results Overall, a total of eight studies comprising 2979 patients were included. When generally comparing TP53 mutation group with TP53 wild-type group, we confirmed the prognostic value of poor OS of TP53 in EGFR mutant lung cancers (HR 1.73, 95% CI 1.22–2.44, P = 0.002). In subgroup analysis of OS, the prognostic value was maintained in patients treated with EGFR tyrosine kinase inhibitors (TKIs) but not in those treated with non-targeted therapy (HR 2.29, 95% CI 1.39–3.76, P = 0.001), and was also maintained in patients with advanced-stage lung cancers rather than those of all stages (HR 2.00, 95% CI 1.11–3.61, P = 0.021). For patients treated with EGFR TKIs, TP53 commutation was predictive of a poor PFS (HR 2.18, 95% CI 1.42–3.36, P < 0.001) but the prognostic value on ORR was not observed (RR 1.15, 95% CI 0.92–1.44, P = 0.212). Additional subgroup analysis based on TP53 mutation subtypes was not pooled due to limited data. Conclusion Generally we confirmed the prognostic value of poor OS and PFS of TP53 commutation in EGFR mutant lung cancers, and it should be further investigated and validated regarding the prognostic role of TP53 mutation subtypes.

Existing challenges of lung cancer screening included non-accessibility of computed tomography (CT) scanners and inter-reader variability, especially in resource-limited areas. The combination of mobile CT and deep learning technique has inspired innovations in the routine clinical practice.This study recruited participants prospectively in two rural sites of western China. A deep learning system was developed to assist clinicians to identify the nodules and evaluate the malignancy with state-of-the-art performance assessed by recall, free-response receiver operating characteristic curve (FROC), accuracy (ACC), area under the receiver operating characteristic curve (AUC).This study enrolled 12,360 participants scanned by mobile CT vehicle, and detected 9511 (76.95%) patients with pulmonary nodules. Majority of participants were female (8169, 66.09%), and never-smokers (9784, 79.16%). After 1-year follow-up, 86 patients were diagnosed with lung cancer, with 80 (93.03%) of adenocarcinoma, and 73 (84.88%) at stage I. This deep learning system was developed to detect nodules (recall of 0.9507; FROC of 0.6470) and stratify the risk (ACC of 0.8696; macro-AUC of 0.8516) automatically.A novel model for lung cancer screening, the integration mobile CT with deep learning, was proposed. It enabled specialists to increase the accuracy and consistency of workflow and has potential to assist clinicians in detecting early-stage lung cancer effectively.

Lung cancer is the leading cause of cancer death and there have been clinical prediction models. This study aimed to evaluate the diagnostic performance of published models and create new models to evaluate the probability of malignant solitary pulmonary nodules (SPNs) in Chinese population. We consecutively enrolled 2061 patients with SPNs from West China Hospital between January 2008 and December 2016, each SPN was pathologically confirmed. First, four published prediction models, Mayo clinic model, Veterans Affairs (VA) model, Brock model and People’s Hospital of Peking University (PEH) model were validated in our patients. Then, utilizing logistic regression, decision tree and random forest (RF), we developed three new models and internally validated them. Area under the receiver operating characteristic curve (AUC) values of four published models were as follows: Mayo 0.705 (95% CI 0.658–0.752, n = 726), VA 0.64 6 (95% CI 0.598–0.695, n = 800), Brock 0.575 (95% CI 0.502–0.648, n = 550) and PEH 0.675 (95% CI 0.627–0.723, n = 726). Logistic regression model, decision tree model and RF model were developed, AUC values of these models were 0.842 (95% CI 0.778–0.906), 0.734 (95% CI 0.647–0.821), 0.851 (95% CI 0.789–0.914), respectively. The four published lung cancer prediction models do not apply to our population, and we have established new models that can be used to predict the probability of malignant SPNs.

BackgroundPrimary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor and often misdiagnosed as squamous carcinoma. In the current study, clinical characteristics and outcome of primary pulmonary LELC were systematically compared with pulmonary squamous carcinoma.MethodsForty-two cases of primary pulmonary LELC and 134 squamous carcinomas were enrolled retrospectively. Characteristic and prognosis difference between the two groups was compared, and the independent prognostic factor for pulmonary LELC was identified as well.ResultsIn comparison to squamous carcinoma, pulmonary LELC was more common in women with a younger median age and less smokers. LELC seemed to be smaller in diameter on computed tomography (CT) scans than squamous carcinoma, with scarce spiculation and vascular convergence signs. Epstein-Bar virus-encoded RNA (EBER) by in-situ hybridization was detected in 33 LELC cases, among whom 27 ones were positive in serum EBV-DNA examination. LELC patients presented a much longer median progression-free survival (PFS) than squamous carcinoma. Positive serum EBV-DNA, distant lymph node invasion, advanced clinical stage and receiving radiotherapy were correlated with the shorter PFS in LELC patients. However, only positive serum EBV-DNA was the independent PFS predictor.ConclusionPulmonary LELC looks like distinct from squamous carcinoma. Middle-aged women and nonsmokers are comparatively predominated. CT features of pulmonary LELC are relatively less-malignant. Correspondently, the progression of pulmonary LELC is seemingly favorable than squamous carcinoma and the positive serum EBV-DNA appears to be the predictor of PFS.

Since the discovery of X-rays at the end of the 19th century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics. These techniques have given rise to genomics, proteomics, metabolomics and other systems biology subspecialties, including radiogenomics. Radiogenomics is an important revolution in the traditional visually identifiable imaging technology and constitutes a new branch, radiomics. Radiomics is aimed at extracting quantitative imaging features automatically and developing models to predict lesion phenotypes in a non-invasive manner. Here, we summarize the advent and development of radiomics, the basic process and challenges in clinical practice, with a focus on applications in pulmonary nodule evaluations, including diagnostics, pathological and molecular classifications, treatment response assessments and prognostic predictions, especially in radiotherapy.

RPS6KB1 is the kinase of ribosomal protein S6 which is 70 kDa and is required for protein translation. Although the abnormal activation of RPS6KB1 has been found in types of diseases, its role and clinical significance in non-small cell lung cancer (NSCLC) has not been fully investigated. In this study, we identified that RPS6KB1 was over-phosphorylated (p-RPS6KB1) in NSCLC and it was an independent unfavorable prognostic marker for NSCLC patients. In spite of the frequent expression of total RPS6KB1 and p-RPS6KB1 in NSCLC specimens by immunohistochemical staining (IHC), only p-RPS6KB1 was associated with the clinicopathologic characteristics of NSCLC subjects. Kaplan-Meier survival analysis revealed that the increased expression of p-RPS6KB1 indicated a poorer 5-year overall survival (OS) for NSCLC patients, while the difference between the positive or negative RPS6KB1 group was not significant. Univariate and multivariate Cox regression analysis was then used to confirm the independent prognostic value of p-RPS6KB1. To illustrate the underlying mechanism of RPS6KB1 phosphorylation in NSCLC, LY2584702 was employed to inhibit the RPS6KB1 phosphorylation specifically both in lung adenocarcinoma cell line A549 and squamous cell carcinoma cell line SK-MES-1. As expected, RPS6KB1 dephosphorylation remarkably suppressed cells proliferation in CCK-8 test, and promoted more cells arresting in G0-G1 phase by cell cycle analysis. Moreover, apoptotic A549 cells with RPS6KB1 dephosphorylation increased dramatically, with an elevating trend in SK-MES-1, indicating a potential involvement of RPS6KB1 phosphorylation in inducing apoptosis. In conclusion, our data suggest that RPS6KB1 is over-activated as p-RPS6KB1 in NSCLC, rather than just the total protein overexpressing. The phosphorylation level of RPS6KB1 might be used as a novel prognostic marker for NSCLC patients.

Overexpression of Raf‐1 has commonly been observed in solid tumors including non‐small cell lung cancer (NSCLC). The objective of this study was to investigate whether overexpression of Raf‐1, phosphorylated‐Raf‐1 (p‐Raf‐1) or both correlates with poor survival rate in NSCLC patients and to explore associations between expression of these proteins and NSCLC cell fate both in vitro and in vivo. Expression of Raf‐1 and p‐Raf‐1 were detected by immunohistochemistry in tumor specimens from 152 NSCLC patients and associations between their expression and the clinicopathological characteristics were assessed. Five‐year median survival rate of patients were analyzed by Kaplan–Meier method, log‐rank test and Cox regression. Cell fate was compared between normal tumor cells and those with Raf‐1 silencing, in both the adenocarcinoma cell line A549 and xenografted mice that were infected with the A549 cell line. The incidence of overexpression of both Raf‐1 and p‐Raf‐1 in NSCLC was much higher than normal control (P

The importance of apoptosis during the process of inhibiting tumorigenesis has been recognized. The role of BH3-only proapoptotic protein Bcl-2-associated death (BAD) in tumor growth remains controversial. The aim of this study was to explore the role of BAD in lung cancer cells. Our study showed that expression of BAD was upregulated in A549 cells by a recombinant lentivirus overexpressing BAD. In vitro, BAD overexpression significantly inhibited A549 cell proliferation and induced apoptosis in cell proliferation and apoptosis assays, respectively. The effect of BAD on A549 cells was studied in tumor xenograft of nude mice and the results showed that the tumor volume in the experimental group was smaller than the control groups. Further, immunohistochemical technique was used to determine the cell proliferation and apoptosis status of the lung tumor xenograft cells. This demonstrated that the in vivo and in vitro results were consistent. Taken together, our results indicate that overexpression of BAD inhibits the growth of A549 cells in vitro and in vivo, through inhibiting cell proliferation and inducing apoptosis. Thus, BAD could be a potential therapeutic target.

The mammalian Janus kinase (JAK) family plays a critical role in cytokine/growth factor signalling pathways and is associated with human cancers. In this study, we explored the role of JAK1 in the non-small cell lung cancer (NSCLC) cell line A549 and its molecular crosstalk with the phosphatidyl inositol-3-kinase (PI3K)/mammalian target of the rapamycin (mTOR) pathway. One hundred and two NSCLC and 50 normal lung specimens were collected after surgical resection. JAK1 expression and phosphorylation were determined via immunohistochemical staining (IHC) assay. A stable knockdown of JAK1 was performed in A549 cells by RNA interference. Stable cell proliferation, cell cycle, apoptosis, and invasion were characterised in vitro. Tumourigenicity was analysed in vivo. The NSCLC xenograft protein expression of PI3K/mTOR pathway molecules was determined by Western blot assay. JAK1 expression was higher in NSCLC tissues than in normal lung tissues (P

Background Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is involved in multiple cellular bioactivities. However, its clinicopathological significance in non-small cell lung cancer (NSCLC) is poorly understood. Methods Expressions of total rpS6 (t-rpS6) and phosphorylated rpS6 (Ser235/236, p-rpS6) were detected immunohistochemically in 316 NSCLC tissues and 82 adjacent controls, followed by statistical evaluation of the relationship between proteins expressions and patients’ survivals to identify their prognostic values. Cytological experiments with overexpressing or silencing rpS6 by lentivirus in human bronchial epithelial (HBE) and NSCLC cell lines were performed to explore potential mechanisms by which rpS6 affects the clinical development of NSCLC. Additionally, specific RNA interference for Akt1, Akt2, Akt3, Akt inhibitor and subsequent cellular bioactivity tests were employed as well to investigate the upstream regulation of rpS6. Results Positive rates of t-rpS6 and p-rpS6 were both significantly increased in NSCLC tissues, compared with controls (82.91 vs 62.20 % for t-rpS6; 52.22 vs 21.95 % for p-rpS6; both P

Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.

Background Glycogen synthase kinase 3 beta (GSK3β) is centrally involved in diverse cellular processes, including proliferation and apoptosis. This study aimed to investigate the influence of GSK3β expression on the prognosis of human non-small cell lung cancer (NSCLC) and the effects of GSK3β inhibition in NSCLC cell lines. Methods Immunohistochemical and western blot assays were used to evaluate the GSK3β expression level in human NSCLC tissues. Lentiviral RNA interference was performed to inhibit the expression of GSK3β in the A549, H292, H1299 and SK-MES-1 cell lines. Cell survival, apoptosis and motility were evaluated in vivo and in vitro. Results The levels of GSK3β were greater in NSCLC tissues (n = 211) than in control tissues (n = 194) (P

Background Pulmonary sclerosing hemangioma (SH) is an uncommon tumor. The aim of this study was to identify the origin of pulmonary SH and summarize its clinicopathologic features. Methods Data of 26 cases of pulmonary SH were collected and reviewed, including their clinical symptoms, chest radiological examinations, treatments, and pathological findings. Results Female patients of pulmonary SH were markedly frequent (n=23, 88.46%). Solitary mass or nodule in the lung fields was the most common manifestation (n=24, 92.31%), especially in the right middle lobe (n=9, 34.62%). There were two kinds of tumor cells: lining cells and round cells. All tumors contained a mixture of papillary, solid, sclerotic, and hemorrhagic patterns. Immunohistochemistry with a variable number of antibodies was performed for some cases. All of the detected specimens revealed strong reaction of lining cells with epithelial markers, such as thyroid transcription factor-1 (TTF-1), epithelial membrane antigen (EMA), cytokeratin (CK), pancytokeratin (PCK), and cytokeratin 7 (CK-7), while round cells were positive with TTF-1 and EMA. Until the end of last contact, none of the patients died or suffered from the recurrence of the disease after surgical treatment. Conclusions Pulmonary SH is a unique neoplasm of the lung with a characteristic solitary mass or nodule. Pulmonary epithelium might be the primary origin of the tumor cells.

The standard definition of high-risk individuals for lung cancer was not uniform and the value of chest digital radiography (DR) in lung cancer screening was still unproven. The aim of this study was to assess whether the original questionnaire named as "Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer" combined with DR examinations could detect early stage of lung cancer effectively. The Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer had been designed in previous studies. Subjects with scores over 116 points were regarded as high-risk individuals and underwent the current DR scans at least once a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of the scoring questionnaire combined with DR scans was estimated by 3-year results. Among 1,537 subjects, 13, 11, and 7 were diagnosed with lung cancer in the first, second, and third year, respectively, indicating the detection rate of 2.02 % (31/1,537). In addition, 77.42 % (24/31) of the patients were in stage I and 51.61 % (16/31) were adenocarcinomas. For the 31 cases, 28 were defined as detected cancers, while the other three were interval ones, only accounting for 0.20 % (3/1,504) of individuals with negative judgments. The protocol of Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with DR scans is a cost-effective and safe approach to detect early stage of lung cancer.

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

As a rare disease, pulmonary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (PMZL-MALT), is often misdiagnosed. The aim of this study is to summarize the clinical and pathological features of this disease and improve the awareness of doctors.Seven cases (female 5, male 2) diagnosed of PMZL-MALT in West China Hospital between November 2008 and November 2010, were analyzed retrospectively, including their symptoms, radiological findings, pathological examinations, treatment and prognosis.The median age of the patients were 62 years old (range 34-79 years). Six patients suffered from cough and sputum. Pulmonary consolidation was the most frequent manifestation, leading a misdiagnosis of pneumonia with CT examinations. Pathological diagnosis was obtained via fiberoptic bronchoscopy in six patients and percutaneous pulmonary biopsy for the rest one. In the seven cases, immunohistochemical results showed CD20(+), CD79a(+), while CD3 epsilon(-), CD5(-), CyclinD1(-), CD10(-), Bcl-2(-) and CD30(-). Additionally, the expression of Ki-67 was below 10%. Further PCR analysis showed evidence of immunoglobulin heavy chain gene rearrangement in tissues from six subjects. Based on the disease location and patients' wishes, compared with two cases just receiving symptomatic treatments, the other five ones took in chemotherapies.Since there were no specific clinical features for patients of PMZL-MALT, histopathological examination was the only effective means to confirm the diagnosis.

BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has been shown to contribute to tumorigenesis. This study explored protein expression profiles of mTOR pathway and the relationship with prognosis in patients with nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via immunohistochemical staining assay. The clinical prognostic values of both single and combined protein expression were investigated with univariate and multivariate survival analysis. RESULTS: Compared with normal lung tissues, the protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR expression was associated with histological differentiation, histological type, lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate analysis showed that the combination of p-mTOR/p-P70S6K is an independent prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides clinical evidence that activated components of mTOR pathway, not total protein, are predictors of poor prognosis in NSCLC. Moreover, evaluating protein-expression profiles of these molecules might be a new strategy for individual therapy in subjects with NSCLC. Cancer 2011;. © 2011 American Cancer Society.