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ObjectiveTo reveal the differences of the related pathogenicity gene mutations between sebaceous adenocarcinoma （SC） of scalp and sebaceous adenoma （SA） of scalp on whole exome level. MethodsWhole exome sequencing was performed on a SC sample and a SA sample by Illumina Hiseq 2500 platform. Suspicious single nucleotide variation sites were selected for mutation conservation and functional analysis. SciClone was used to track subclone evolution and clonal map information was obtained for each tumor sample. The high-frequency significant gene mutations in the tumor sample were screened by MutSigCV software， and compared with the known driver genes. ResultsTwo driver genes TFDP1 and ACVR1B harboring mutations in scalp SC compared to SA were found. ConclusionsThe finding of mutation in driver genes TFDP1 and ACVR1B should be confirmed in a large cohort， which might reveal the mechanism of scalp SC development and find a therapeutic target for SC.
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With the discovery of lung cancer targets and drug development, targeted therapy has improved the clinical prognosis of non-small cell lung cancer (NSCLC) with driver gene mutations. Immune checkpoint inhibitors (ICIs) have shown good efficacy in driver gene-negative NSCLC. Although some patients with driver gene mutations benefited significantly from the corresponding targeted therapy, they did not respond well to immunotherapy. In most clinical trials and daily practice, patients with NSCLC and driver gene mutations such as EGFR and ALK are excluded or only account for a minority of patients. Applying immunotherapy to patients with driver gene mutations, selecting the best treatment regimens among targeted therapy, chemotherapy, and immunotherapy, and formulating the optimal treatment strategy are crucial to improve the prognosis of patients with advanced NSCLC and driver gene mutations. This paper reviews the characteristics of tumor immune microenvironment with different driver gene mutations and the application of immunotherapy for patients with NSCLC and different driver gene mutations.
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Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has "driver gene mutations" and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation. .
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Humans , Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy , Lung Neoplasms/therapy , Molecular Targeted Therapy , MutationABSTRACT
Venous thromboembolism (VTE) is one of the common complications of lung adenocarci-noma. The state of the driver genes of lung adenocarcinoma is related to the risk of VTE. The common driver genes include epidermal growth factor receptor, anaplastic lymphoma kinase, c-ros oncogene 1 receptor kinase and Kirsten rat sarcoma viral oncogene, etc.. Based on the study of the correlation between lung adenocarci-noma driver genes and VTE, it is of great significance for the early clinical prevention of VTE in patients with lung adenocarcinoma to screen out patients with high risk of VTE according to the state of the driver genes and finally evaluate the risk of VTE in patients with lung adenocarcinoma by combining conventional risk factors with the driver genes.
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In recent years, molecular targeted therapy has effectively improved the prognosis of advanced non-small cell lung cancer (NSCLC) patients with driver gene-positive, of which the efficacy is particularly significant for NSCLC patients with human epidermal growth factor receptor gene mutation, echinoderm microtubule-associated protein-4-anaplastic lymphoma kinase fusion gene, ROS1 gene rearrangement, etc. The selection of targeted therapy drugs is particularly important for advanced NSCLC patients with positive driver genes.
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BACKGROUND@#New treatment methods such as targeted therapy and immune checkpoint inhibitors have been applied to lung cancer patients. It is necessary to further understand the patients with lung cancer combined with pulmonary tuberculosis with the development of lung cancer research. The purpose of this study was to analyze the clinical characteristics of lung cancer patients with pulmonary tuberculosis, the status of driver genes, and their relationships.@*METHODS@#A retrospective analysis was performed on 405 patients with lung cancer and pulmonary tuberculosis hospitalized in our hospital from January 2014 to December 2019. The relationship between clinical characteristics and driver genes status was analyzed.@*RESULTS@#Among the 405 patients with lung cancer combined with pulmonary tuberculosis, 77.3% were male and 85.3% were patients with a history of smoking. The pathological type was mainly lung adenocarcinoma. When there were cavities in chest computed tomography (CT) , squamous cell carcinoma was the main type. 214 patients underwent driver genes testing. The epidermal growth factor receptor (EGFR) gene mutation rate was 35.9%, of which 41.8% were exon 19 deletion mutations and 50.9% were exon 21 L858R mutations. When there were cavities in the chest CT, the EGFR mutation rate was significantly reduced (16.1%). The positive rate of anaplastic lymphoma kinase (ALK) fusion gene detection was 2.5%, the mutation rate of c-ros oncogene 1 receptor kinase (ROS1) gene was 1.9%, the mutation rate of V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene was 1.1%, and the mutation rate of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene was 10.1%. The genetic mutation rate of female patients with lung cancer and pulmonary tuberculosis was 50.0%, and that of men was 27.9%.@*CONCLUSIONS@#Patients with lung cancer and pulmonary tuberculosis are predominantly male with smoking history. Adenocarcinoma is the most common pathological type. The positive rate of gene mutation was not significantly different from that of simple lung cancer, but when there were cavities in the chest image, the genetic mutation rate was significantly reduced.
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Leptomeningeal metastasis (LM) is one of the serious complications of advanced non-small cell lung cancer (NSCLC), although the incidence is not high, the clinical symptoms are severe and the prognosis is poor. LM is prone to occur in patients with positive driver gene than negative. At present, the treatment of LM mainly includes molecular targeted therapy, systemic chemotherapy, whole brain radiotherapy, intrathecal chemotherapy and immunotherapy. Although there are many treatments, the efficacy of LM is still unsatisfactory. This article reviews the drug therapy of sensitive driver gene positive NSCLC LM.
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Lung micropapillary adenocarcinoma is characterized by frequent metastasis, lymph node infiltration, high recurrence rate and low overall survival rate as a high-grade lung adenocarcinoma. Special oncogenic pathway is activated and immune microenvironment is established in this subtype of tumor. This article reviews the Pathological phenomena and molecular features of micropapillary adenocarcinoma studied in recent years, aiming to deepen the understanding of micropapillary lesions and lay the foundation for formulating specific treatment strategies. .
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In recent years, the checkpoint inhibitors targeted programmed cell death 1 (PD-1) and its ligand 1 (PD-1 ligand, PD-L1) achieved landmark significance in treating a variety of cancers including non-small cell lung cancer (NSCLC). However, current immunotherapy is not precise enough, only 15%-20% of the unselected patients can benefit from the therapy, and there is a possibility of hyperprogression (HP). Therefore, how to select the dominant population is crucial. Although many studies have emphasized the importance of PD-L1 and tumor mutation burden (TMB) and other indicators to guide immunotherapy, current PD-L1 expression level and mutation load cannot be used as a decisive and excluded predictive marker based on various obstacles. With the deepening of research, we found that there is a close relationship between lung cancer-driver gene mutation and aberrant activation of PD-1/PD-L1 signal pathways, and the correlation between gene mutation and immunotherapy efficacy has broad research value. This article will revolve around the above issues. .
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Humans , Carcinoma, Non-Small-Cell Lung , Genetics , Allergy and Immunology , Therapeutics , Immunotherapy , Methods , Lung Neoplasms , Genetics , Allergy and Immunology , Therapeutics , Treatment OutcomeABSTRACT
BACKGROUND@#Non-small cell lung cancer (NSCLC) with neuroendocrine differentiation (NED) was a new pathologic type and uncommon in clinics. The aim of this study is to observe the relationship between clinical pathologic characteristics, imagination, biological behavior and prognosis in NSCLC-NED.@*METHODS@#The clinical data of 47 patients with NSCLC-NED admitted from January 2009 to November 2017 in the Fifth Medical Center of General Hospital of People's Liberation Army were collected. The demographic data and imaging characteristics were summarized. Pathological features, treatment and prognosis, analysis of the correlation between different factors and prognosis.@*RESULTS@#Of the 47 patients with NSCLC-NED, the median age was 61 years (45 years-78 years), 38 males and 9 females; 37 were poorly differentiated cancer with NED, and 10 were middle differentiated cancer with NED; 2 cases of driving gene positive (1 case of EGFR sensitive mutation, 1 case of ALK fusion), objective response rate (ORR) of first-line chemotherapy was 34.5%, and median progression-free survival (PFS) was 4 months; the median overall survival (OS) was 11 months, and only 2 cases (4.2%, 2/47) of OS were over 2 years.@*CONCLUSIONS@#NSCLC-NED is different from simple NSCLC or pulmonary neuroendocrine tumors. Males, ≤70 years old, severely smoking, and patients with lower tumor differentiation often have NED, and most of them are stage IV. This type of patient-driven gene positive proportion is lower than the general adenocarcinoma population, less sensitive to chemotherapy, and the overall survival is shorter, indicating a poor prognosis.
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Brain is the most common site of lung cancer metastasis, and the incidenceis are higher if patients have driver gene mutation. Patients with brain metastasis have a poor prognosis; further, different treatment methods affect the disease status and prognosis. In recent years, with the development of precision medicine, gradual progress has been made in treatments for lung cancer patients with brain metastasis, especially for those with driver gene mutations. This review first highlights the challenges of brain metastasis treatments, and then summarizes the research progress regarding targeted therapies for patients with driver gene mutation-positive lung cancer and brain metastasis. This review could help guide clinical decision making for individualized treatment in daily clinical practice.
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Objective To analyze driver genes status and its clinical characteristics of advanced lung adenocarcinoma, then evaluate the status of first-line treatment in a single centric real-world. Methods EGFR, ALK, ROS-1 gene in 204 advanced lung adenocarcinoma tissue were tested by ARMS-PCR method. And the relationship between driver genes status and clinical characteristics was analyzed as the first line treatment in real clinical practice. Results The positive rate of driver genes status in 204 advanced lung adenocarcinoma was 53.9％ (110/204) , including EGFR mutation 46.1％ (94/204) , ALK positive 6.4％ (13/204) and ROS1 positive 1.5％ (3/204). The driving genes status was significantly correlated with gender, smoking history, tumor staging and serosal invasion (P < 0.05). There were significantly differences among the proportion of first-line standard treatment in different subgroup (P = 0.000) , the first-line standard treatment rate of EGFR mutation, ALK/ROS1 positive and drive gene negative were 77.7％, 37.5％, and 46.8％ respectively. And the ratio of using 1 st generation EGFR-TKIs in all patients is 70.6％ (60/85). Conclusion More than half of advanced lung adenocarcinoma have driver genes changes, and EGFR-TKI first-line treatment has higher acceptability in real-word.
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In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
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Humans , Carcinoma, Non-Small-Cell Lung , Diagnosis , Drug Therapy , Genetics , Pathology , Lung Neoplasms , Diagnosis , Drug Therapy , Genetics , Pathology , Mutation , PrognosisABSTRACT
Brain metastasis was a common metastasis site and leading cause of death in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors had improved survival of NSCLC patients with positive drive gene. It also brings good news to NSCLC patients with positive drive gene and brain metastases. However, there is still no effective treatment for NSCLC patients with drive gene-negative and brain metastases. In recent years, immunotherapy has made breakthrough progress and become important first and second line treatment options of NSCLC especially in patients with drive gene-negative. The role of immunotherapy in specific populations of NSCLC-brain metastasis patients, especially drive gene-negative patients has become the focus of attention. In this report, we review the research progress of immunotherapy in NSCLC with brain metastases, especially in driver-negative patients, analyze the limitations of existing research and future challenge. .
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Humans , Brain Neoplasms , Allergy and Immunology , Therapeutics , Carcinoma, Non-Small-Cell Lung , Genetics , Pathology , Immunotherapy , Methods , Lung Neoplasms , Genetics , Pathology , Patient SelectionABSTRACT
Objective: To detect eight highly related driver genes in non-small cell lung cancer (NSCLC), and to analyze the relationship between gene variations and clinical-pathological features. Methods: We collected 212 NSCLC samples from Tianjin Medical University Cancer Institute and Hospital, and sequenced eight genes which are EGFR, KRAS, BRAF, ALK, MET, ERBB2, ROS1 and RET. Results: EGFR gene variation rate was as high as 52.8%, followed by KRAS (8.5%), ALK (8.0%), ERBB2 (6.1%), MET (3.8%), BRAF (1.4%), RET (0.9%) and ROS1 (0.9%) in eight detecting genes, at least one driver gene variant was detected in 75% samples, and driver gene variant showed strong mutual exclusion. The most common EGFR mutations were 19 exon deletion and L858R mutation, and the mutation of EGFR T790M was accompanied by the above two mutations. The proportion of non-EGFR T790M mutations in patients with exon 19 dele-tion was lower than that of L858R mutations (P=0.04). There were 15.2% patients with EGFR mutation accompanied by EGFR amplifica-tion, and the proportion of patients with EGFR mutation frequency greater than 40% with EGFR amplification was higher than that without EGFR amplification (P<0.01). Women, non-smoking, patients with adenocarcinoma were prone to carry EGFR especially EGFR sensitive mutations (P<0.01). Patients with lung adenocarcinoma (P=0.013), late clinical stage (P=0.048), and lymph node metastasis (P=0.027) had a higher proportion of EGFR amplification. The incidence of KRAS mutation was higher in men, left lung cancer and smoking patients (P=0.009, P=0.048, P=0.037). Patients with non-KRAS mutations, ALK fusions were younger (P=0.005, P=0.031), and with KRAS mutations were older (P=0.055). Conclusions: Next-generation sequencing (NGS) can simultaneously detect eight highly re-lated driver genes in NSCLC patients to provide evidence for clinicians. NGS based on detection of multiple genes provides more possi- bilities for individualized diagnosis and treatment of NSCLC.
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Objective To investigate the relationship between the driver genes mutation and the survival in patients with pulmonary adenocarcinoma brain metastasis. Methods We enrolled 200 patients with pulmonary adenocarcinoma brain metastasis confirmed histologically from Jan 2013 to Dec 2015, and tested EGFR, KRAS, ALK, Her-2 gene mutation, analyzed the relationship between EGFR gene mutation and clinicopathological data and prognosis of the patients.Results The mutation rates of EGFR, KRAS, ALK and Her-2 gene mutation were 48.5％, 5.5％, 6.5％, 3.5％, respectively. Compared with EGFR gene mutation patients, the sex, age, BMI, differentiation were significant different (P＜0.05), however, the smoking was not significant different (P＞0.05). Patients with EGFR gene mutation who received targeted therapy survived longer than who did not receive targeted therapy, (28.0 ±4.5) months vs (11.2 ±1.4) months. By Log Rank (Mantel-Cox), the median survival time between the two groups was statistically significant (P＜0.05).Conclusions The mutation rate of EGFR gene mutation was high in patients with pulmonary adenocarcinoma brain metastasis, and the patients will survivel longer by targeted therapy.
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With the rapid development of targeted therapy for lung cancer , dramatic changes are under way in the therapeutic means , drugs as well as the treatment concept .This article gives representation of the precision targeted therapy from the following 3 aspects:basic requirements for detection before treatment , higher requirements for selecting targeted drugs according to the subtypes of driver genes , and perfect requirements for dynamic adjustment with molecular changes for drug resistance .Through this review , the essence of precision medicine and whole process management for lung cancer might be better understood .
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Background and purpose:Lung cancer is the leading cause of morbidity and cancer-related mortality worldwide. A variety of driver genes were detected in lung cancer. Studies have shown that different gene mutations of lung cancer were found between different races. Most of Uyghurs live in Xinjiang, accompanied by a high morbidity of lung cancer. This study aimed to investigate the expression of driver genes in Uyghur patients with lung cancer in Xinjiang, China.Methods:This study collected the tissue specimens of 43 Uyghur patients with lung cancer, with a very different method to detectEGFR gene expression. real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR) was used to detectK-ras,ALK,ROS1, mutatedBRAF andPIK3CA gene expression. Analysis of the correlation between lung cancer gene mutations in Uyghur and clinical features of patients with lung cancer were performed.Results:Among 43 cases of specimens,EGFR mutation rate was 11.63%, while theEGFR gene mutation rates in adenocarcinoma and squamous cell carcinoma were 26.67% and 4.76%, respectively.EGFR gene mutation was not detected in large cell carcinoma, adenosquamous carcinoma and small cell lung cancer.EGFR gene mutation rate in patients with adenocarcinoma (26.67%) was signiifcantly higher than that in other types of lung cancer (3.57%). The difference was statistically signiifcant (P=0.024). There were 6 patients withK-ras12/13 heterozygous mutation, and the mutation detection rate was 16.28% (6/43). There were 2 patients withPIK3CA heterozygous mutation, and the mu-tation detection rate was 4.65% (2/43).EGFR andK-ras mutations occurred simultaneously in 1 case. No relationship was found betweenEGFR mutations and age, gender, smoking status, TNM staging, ECOG score among Uyghur lung cancer patients. This study did not ifnd mutation inALK,ROS1 fusion gene andBRAF gene among the 43 specimens. Conclusion:Compared with Asian populations, Xinjiang Uyghur patients with lung cancer have a lower rate ofEGFR mutations and a higher rate ofK-ras mutations, which is similar to the characteristics of European Caucasians.
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Objective:To establish a method based on the iPLEX analysis of MassARRAY mass spectrometry platform to detect multiplex genetic mutations among Chinese lung cancer patients. Methods:We reviewed the related literature and data of lung cancer treatments. We also determined 99 mutation hot spots in 13 target genes, namely, EGFR, KRAS, ALK, FGFR1, FGFR2, FGFR3, PIK3CA, BRAF, PTEN, MET, ERBB2, AKT1, and STK11, which are closely related to the pathogenesis, drug resistance, and metastasis of lung cancer and are associated with relevant transduction pathways. A total of 297 primers comprising 99 paired forward and reverse amplification primers and 99 matched extension primers were designed by using Assay Design in accordance with the mutation label and format requirements of the MassARRAY platform. The detection method was established by analyzing eight cell lines and six lung cancer specimens;the proposed method was then validated through comparisons with a LungCarta kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results:The proposed method could detect multiplex genetic mutations in the lung cancer cell lines, and this finding is consistent with that observed using previously reported methods. The proposed method could also detect such mutations in clinical lung cancer specimens;this result is also consistent with that observed by using the LungCarta kit. However, an FGFR2 mutation was detected only by using the proposed method. The measured sensitivity and specificity were 100%and 96.3%, respectively. Conclusion:The proposed MassARRAY technology-based method could detect multiplex genetic mutations among Chinese lung cancer patients. Indeed, the proposed method can be potentially applied to detect mutations in cancer cells.