[Research Advances of RAD51AP1 in Tumor Progression and Drug Resistance].

The genomic instability may lead to an initiation of cancer in many organisms. Homologous recombination repair (HRR) is vital in maintaining cellular genomic stability. RAD51 associated protein 1 (RAD51AP1), which plays a crucial role in HRR and primarily participates in forming D-loop, was reported as an essential protein for maintaining cellular genomic stability. However, recent studies showed that RAD51AP1 was significantly overexpressed in various cancer types and correlated with poor prognosis. These results suggested that RAD51AP1 may play a significant pro-cancer effect in multiple cancers. The underlying mechanism is still unclear. Cancer stemness-maintaining effects of RAD51AP1 might be considered as the most reliable mechanism. Meanwhile, RAD51AP1 also promoted resistance to radiation therapy and chemotherapy in many cancers. Thus, researches focused on RAD51AP1, and its regulatory molecules may provide new targets for overcoming cancer progression and treatment resistance. Here, we reviewed the latest research on RAD51AP1 in cancers and summarized its differential expression and prognostic implications. In this review, we also outlined the potential mechanisms of its pro-cancer and drug resistance-promoting effects to provide several potential directions for further research.
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Mediastinal lymph node dissection versus spared mediastinal lymph node dissection in stage IA non-small cell lung cancer presented as ground glass nodules: study protocol of a phase III, randomised, multicentre trial (MELDSIG) in China.

INTRODUCTION: Radical surgery including mediastinal lymph node dissection is the standard treatment for early-stage non-small cell lung cancer (NSCLC). About 50% lung nodules are pure ground glass or part-solid nodules, which are predominantly clinical stage IA NSCLC. Non-solid nodules rarely develop mediastinal lymph node metastasis. METHOD AND ANALYSIS: A phase III study was started in China to evaluate the non-inferiority in overall survival of spared mediastinal lymph node dissection compared with mediastinal lymph node dissection in stage IA NSCLC. A total of 1362 patients will be enrolled from 4 institutions in 2-3 years. The second endpoints are relapse-free survival and perioperative data, including duration of hospitalisation, duration of chest tube placement, operation time, blood loss. ETHICS AND DISSEMINATION: This protocol has been reviewed and approved by the Clinical Research Review Board of Tianjin Medical University Cancer Institute and Hospital. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04631770.

[Preliminary Recommendations on the Timing of Lung Surgery after 
Novel Coronavirus Infection in Patients with Pulmonary Nodules and Lung Cancer].

In recent years, the corona virus disease 2019 (COVID-19) pandemic has had a huge impact on the global medical, political and economic fields. Since the beginning of the COVID-19 epidemic, our understanding of the impact of COVID-19 has grown exponentially. Recently, the COVID-19 epidemic has changed rapidly in China, and there has been controversy over how to carry out surgical operations for patients with lung neoplastic lesions. Some studies have shown that lung cancer patients undergoing surgery are more likely to experience respiratory failure and perioperative death after contracting COVID-19 than the general population, however, delays in cancer treatment are also associated with increased mortality among these patients. In particular, the novel coronavirus Omikron variant has a higher transmissibility and may escape the immunity obtained through the previous novel coronavirus infection and vaccination. In order to minimize the risk of novel coronavirus infection in surgical patients, it is necessary to develop new treatment guidelines, expert consensus and preventive measures. However, the current rapid change of the epidemic situation has led to insufficient time and evidence to develop guidelines and consensus. Therefore, thoracic surgeons need to evaluate specific patient populations at higher risk of severe complications before surgery and weigh the benefit of surgical treatment against the risk of novel coronavirus infection. We try to give some recommendations on lung surgery during the current domestic epidemic situation based on the guidelines and consensus of oncology and thoracic surgery organizations in different regions on lung surgery.
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Neutrophil infiltration associated genes on the prognosis and tumor immune microenvironment of lung adenocarcinoma.

The neutrophils exhibit both anti-tumor and pro-tumor effects in cancers. The correlation between neutrophils and tumor development in lung adenocarcinoma (LUAD) is still uncertain, possibly due to a lack of specific neutrophil infiltration evaluation methods. In this study, we identified 30 hub genes that were significantly associated with neutrophil infiltration in LUAD through data mining, survival analysis, and multiple tumor-infiltrating immune cells (TICs) analysis, including TIMER, CIBERSORT, QUANTISEQ, XCELL, and MCPCOUNTER. Consensus clustering analysis showed that these 30 hub genes were correlated with clinical features in LUAD. We further developed a neutrophil scoring system based on these hub genes. The neutrophil score was significantly correlated with prognosis and tumor immune microenvironment (TIME) in LUAD. It was also positively associated with PD-L1 expression and negatively associated with tumor mutational burden (TMB). When combined with the neutrophil score, the predictive capacity of PD-L1 and TMB for prognosis was significantly improved. Thus, the 30 hub genes might play an essential role in the interaction of neutrophils and LUAD, and the neutrophil scoring system might effectually assess the infiltration of neutrophils. Furthermore, we verified the expression of these 30 genes in the LUAD tumor tissues collected from our department. We further found that overexpressed TNFAIP6 and TLR6 and downregulated P2RY13, SCARF1, DPEP2, PRAM1, CYP27A1, CFP, GPX3, and NCF1 in LUAD tissue might be potentially associated with neutrophils pro-tumor effects. The following in vitro experiments demonstrated that TNFAIP6 and TLR6 were significantly overexpressed, and P2RY13 and CYP27A1 were significantly downregulated in LUAD cell lines, compared to BEAS-2B cells. Knocking down TNFAIP6 in A549 and PC9 resulted in the upregulation of FAS, CCL3, and ICAM-1, and the downregulation of CCL2, CXCR4, and VEGF-A in neutrophils when co-culturing with the conditioned medium (CM) from LUAD cells. Knocking down TNFAIP6 in LUAD also led to an elevated early apoptosis rate of neutrophils. Therefore, overexpressed TNFAIP6 in LUAD cancer cells might lead to neutrophils "N2" polarization, which exhibited pro-tumor effects. Further research based on the genes identified in this pilot study might shed light on neutrophils' effects on LUAD in the future.

Systematic pan-cancer analysis showed that RAD51AP1 was associated with immune microenvironment, tumor stemness, and prognosis.

Although RAD51 associated protein 1 (RAD51AP1) is crucial in genome stability maintenance, it also promotes cancer development with an unclear mechanism. In this study, we collected intact expression data of RAD51AP1 from the public database, and verified it was significantly over-expressed in 33 cancer types and correlated with poor prognosis in 13 cancer types, including glioma, adrenocortical carcinoma, lung adenocarcinoma. We further authenticated that RAD51AP1 is up-regulated in several typical cancer cell lines and promotes cancer cell proliferation in vitro. Moreover, we also demonstrated that RAD51AP1 was significantly positively related to cancer stemness score mRNAsi in 27 cancer types and broadly correlated to tumor-infiltrating immune cells in various cancers in a diverse manner. It was also negatively associated with immunophenoscore (IPS) and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) scores and positively correlated with mutant-allele tumor heterogeneity (MATH), tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression in multiple cancers. The tumor stemness enhancing and tumor immune microenvironment affecting functions of RAD51AP1 might compose its carcinogenesis mechanism. Further investigations beyond the bioinformatics level should confirm these findings in each specific cancer.

Advances in the Study of Circadian Genes in Non-Small Cell Lung Cancer.

Circadian genes regulate several physiological functions such as circadian rhythm and metabolism and participate in the cytogenesis and progression of various malignancies. The abnormal expression of these genes in non-small cell lung cancer (NSCLC) is closely related to the clinicopathological features of NSCLC and may promote or inhibit NSCLC progression. Circadian rhythm disorders and clock gene abnormalities may increase the risk of lung cancer in some populations. We collected 15 circadian genes in NSCLC, namely PER1, PER2, PER3, TIMELESS, Cry1, Cry2, CLOCK, BMAL1/ARNTL-1, ARNTL2, NPAS2, NR1D1(REV-ERB), DEC1, DEC2, RORα, and RORγ, and determined their relationships with the clinicopathological features of patients and the potential mechanisms promoting or inhibiting NSCLC progression. We also summarized the studies on circadian rhythm disorders and circadian genes associated with lung cancer risk. The present study aimed to provide theoretical support for the future exploration of new therapeutic targets and for the primary prevention of NSCLC from the perspective of circadian genes. Interpretation of circadian rhythms in lung cancer could guide further lung cancer mechanism research and drug development that could lead to more effective treatments and improve patient outcomes.

Effect of Upper Arm Position Changes on the Occurrence of Ipsilateral Shoulder Pain After Single-Operator Port Thoracoscopy.

BACKGROUND: The aim of this study was to explore the factors associated with the occurrence of ISP after VATS to reduce the incidence of ISP and improve patients' quality of life. METHODS: The data of patients were collected between June 2020 and August 2020 in the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital. The angle of upper arm was measured intraoperatively. The patient's postoperative shoulder function was quantified using the Constant-Murley shoulder function rating score. The proportional hazards model was applied to identify multiple influence factors. RESULTS: A total of 140 eligible patients met criteria. At postoperative day 3, only the age influenced patients' shoulder pain. At postoperative day 14, univariate and multivariate logistic regression analyses showed that age (odds ratio [OR]: 1.098 [1.046-1.152]; P < 0.001) and upper arm Angle A (OR: 1.064 [1.011-1.121]; P = 0.018) were independent risk factors for low shoulder function scores. However, height was its protective factor (OR: 0.923 [0.871-0.977]; P = 0.006). At postoperative day 42, univariate and multivariate logistic regression analyses showed that age (OR: 1.079 [1.036-1.124]; P < 0.001) was a risk factor for low shoulder function scores, and height (OR: 0.933 [0.886-0.983]; P = 0.009) was its protective factor. In contrast, upper arm Angle B was not statistically associated with low shoulder function scores (P>0.05). In addition, the reduction in ipsilateral Shoulder scores after surgery was higher in patients with more than 113° of angle A (P = 0.025). CONCLUSION: ISP was closely related to the angle of anterior flexion of the upper arm on the patient's operative side intraoperatively. The increase in the degree of postoperative shoulder injury is more pronounced for an anterior flexion angle of >113°. Therefore, we recommend that the angle of anterior flexion of the upper extremity should be <113° intraoperatively.

Comparison of Lobectomy and Sublobar Resection for Stage IA Elderly NSCLC Patients (≥70 Years): A Population-Based Propensity Score Matching's Study.

BACKGROUND: To investigate the differences in survival between lobectomy and sub-lobar resection for elderly stage I non-small-cell lung cancer (NSCLC) patients using the Surveillance, Epidemiology, and End Results (SEER) registry. METHOD: The data of stage IA elderly NSCLC patients (≥ 70 years) with tumors less than or equal to 3 cm in diameter were extracted. Propensity-matched analysis was used. Lung cancer-specific survival (LCSS) was compared among the patients after lobectomy and sub-lobar resection. The proportional hazards model was applied to identify multiple prognostic factors. RESULTS: A total of 3,504 patients met criteria after propensity score matching (PSM). Although the LCSS was better for lobectomy than for sub-lobar resection in patients with tumors ≤ 3 cm before PSM (p < 0.001), no significant difference in the LCSS was identified between the two treatment groups after PSM (p = 0.191). Multivariate Cox regression showed the elder age, male gender, squamous cell carcinoma (SQC) histology type, poor/undifferentiated grade and a large tumor size were associated with poor LCSS. The subgroup analysis of tumor sizes, histologic types and lymph nodes (LNs) dissection, there were also no significant difference for LCSS between lobectomy and sub-lobar resection. The sub-lobar resection was further divided into segmentectomy or wedge resection, and it demonstrated that no significant differences in LCSS were identified among the treatment subgroups either. Multivariate Cox regression analysis showed that the elder age, poor/undifferentiated grade and a large tumor size were a statistically significant independent factor associated with survival. CONCLUSION: In terms of LCSS, lobectomy has no significant advantage over sub-lobar resection in elderly patients with stage IA NSCLC if lymph node assessment is performed adequately. The present data may contribute to develop a more suitable surgical treatment strategy for the stage IA elderly NSCLC patients.

Outcomes of lobectomy on pulmonary function for early stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Lung cancer is the first cause of cancer mortality worldwide. Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. An epidemiological survey discovered that the presence of COPD increases the risk of lung cancer by 4.5-fold. Lobectomy is considered to be the standard surgical method for early stage non-small cell lung cancer (NSCLC). However, the influence of lobectomy on the loss of pulmonary function has not been fully investigated in NSCLC patients with COPD. METHODS: We searched the PubMed database using the following strategies: COPD and pulmonary function test (MeSH term) and lobectomy (MeSH term) from 01 January 1990 to 01 January 2019. We selected the articles of patients with COPD. A total of six studies, including 195 patients with COPD, provided lung function values before and after surgery. RESULTS: Five out of six studies focused on the short-term change of pulmonary function (within 3-6 months) after lobectomy, and the average loss of FEV1 was 0.11 L (range: -0.33-0.09 L). One study investigated the long-term change of pulmonary function (within 1-2 years) after lobectomy, and the average loss of FEV1 was 0.15 L (range: -0.29-0.05 L). CONCLUSIONS: A short-term (3-6 months) loss of pulmonary function after operation is acceptable for lung cancer patients with COPD. However, there may be a high risk of postoperative complications in NSCLC patients with COPD. Therefore, surgical treatment needs to be carefully considered for these patients.

Anterior mediastinal metastasis of primary fallopian tube adenocarcinoma: a case report.

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a malignant tumor of the female genital tract that mostly presents intraperitoneal dissemination in clinical practice. The incidence of upper anterior mediastinal metastasis in PFTCs is extremely rare. We herein report a rare case of PFTC mediastinal metastasis after radical resection. When anterior mediastinal metastasis of an unknown origin is encountered, the possibility of PFTC should be considered. CASE PRESENTATION: A 68-year-old female who was previously diagnosed with PFTC after radical resection of a primary tumor in the fallopian tube was admitted to our department with a right anterior mediastinum mass. Radical resection of the mediastinal mass was performed, and poorly differentiated metastatic adenocarcinoma of the fallopian tube was confirmed. There was no recurrence in the 24 months after the curative operation. CONCLUSION: To our knowledge, no mediastinal metastasis of PFTC has been reported yet. Thus, we presented this rare case indicating the heterogeneity of this malignant disease and to draw attention to the occasional distant metastasis of PFTC in clinical practice.

Secretagogin, a marker for neuroendocrine cells, is more sensitive and specific in large cell neuroendocrine carcinoma compared with the markers CD56, CgA, Syn and Napsin A.

A common method to distinguish large cell neuroendocrine carcinoma (LCNEC) from non-neuroendocrine large cell carcinoma (non-NE LCC) is from using specific immunohistochemistry markers, such as CgA, Syn, CD56 and Napsin A, however, the results remain controversial using these markers. Secretagogin (SCGN) is a newly discovered biomarker of neuroendocrine cells. In the present study, the expression of SCGN in 33 cases of human lung large cell carcinoma (LCC), including 17 cases of LCNEC and 16 cases of non-neuroendocrine (NE) LCC and lung cancer cell lines (A549, H1650, H358, H292 and H661). The association between SCGN expression and the clinicopathological characteristics of patients, including sex, age, clinical stage and metastasis, was analyzed. The results revealed that the different lung cancer cell lines had different expression levels of SCGN, and the SCGN protein was localized in the nucleus and cytoplasm of A549 cells detected using immunofluorescence. A total of 54.5% (18/33) of specimens positively expressed the SCGN protein. Of the 17 patients with LCNEC, only 23.5% (4/17) of cases were CgA positive, 35.29% (6/17) were Syn positive, 41.2% (7/17) were CD56 positive, and 41.2% (7/17) were Napsin A positive. However, SCGN was positively detected in 94.1% (16/17) of patients with LCNEC, which was more frequent compared with that in CgA, Syn, CD56 and Napsin A. Analysis of the clinical characteristics indicated that SCGN expression was only significantly associated with pathological type in patients with lung cancer (P<0.001). Furthermore, a positive correlation was observed between SCGN expression and CgA, Syn, and CD56 expression in patients with LCNEC. SCGN was co-localized with the NE markers (CgA, Syn, and CD56) in A549 lung cancer cells and in LCNEC tissues. Thus, SCGN displayed more sensitivity and specificity in lung cancer cells with NE differentiation. A combined analysis of SCGN and other common NE markers may be a potential tool for diagnosing these tumors.

[Preliminary Recommendations for Lung Surgery during 2019 Novel Coronavirus Disease (COVID-19) Epidemic Period].

In December 2019, China diagnosed the first patient with 2019 novel coronavirus disease (COVID-19), and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of COVID-19. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.

Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma.

BACKGROUND: This study compared tumor-related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment. METHODS: Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype-tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug-pathway network for LUAD was constructed, and molecular docking was carried out. RESULTS: After the integration of 57 LUAD-related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD-related oncogenic pathways were involved in the LUAD drug-pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly. CONCLUSION: Our study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG-028671, may have potential roles for LUAD treatment but require further experimental verification.

Clinical implication of MEN1 mutation in surgically resected thymic carcinoid patients.

Thymic carcinoid is a rare but very aggressive neuroendocrine tumour derived from the neuroendocrine system. Here we report a male patient with thymic atypical carcinoid. Though thymic carcinoid is relatively common, the gene sequencing profile was performed and the gene sequencing result indicated germline multiple endocrine neoplasia type 1 (MEN1) mutation and two somatic mutations on MEN1 gene and no copy number variation or fusion events were detected. It is well-known that the mutation of MEN1 is the typical manifestation of MEN1 syndrome, which is an autosome dominant disease that includes varying combinations of more than 20 endocrine and non-endocrine tumors. In the English literature, 7 cases of solitary thymic carcinoid harboring somatic variants in MEN1 are reported in the absence of other organs involvement as MEN1 syndrome presents. We summarized the clinical features and prognosis of this rare thymic tumor.

Serum microRNA-139-5p is downregulated in lung cancer patients with lytic bone metastasis.

Bone remodeling can be interrupted by tumor cells which leads to an inappropriate balance of osteoblasts and osteoclasts. As the progenitors of osteoblasts, mesenchymal stem cells (MSCs) have been reported to exhibit an abnormal osteogenic differentiation potential in some cancer­related bone lesions. However, the evidence is very limited in terms of the biological alterations of MSCs in the bone metastasis of non­small cell lung cancers (NSCLC). We investigated the expression and function of miR­139­5p in MSC osteogenic differentiation in vitro in normal and NSCLC-exposed condition. Then, we compared the serum miR­139­5p in stage IV lung adenocarcinoma cancer patients with and without lytic bone metastasis. We found that MSCs exhibited a significant increase in miR­139­5p expression after exposure to osteogenic differentiation induction medium. However, Notch1, which was confirmed as a target of miR­139­5p by luciferase and western blot assays, showed a marked downregulated expression together with its pathway downstream factors during MSC osteogenesis. miR­139­5p positively regulated MSC osteogenic differentiation but this effect was abrogated significantly by Notch1 knockdown. After exposure to conditions of lung cancer cells A549 and L9981, MSCs exhibited significant downregulation of miR­139­5p expression and early osteogenic marker ALP activity. Furthermore, we demonstrated that the expression of serum miR­139­5p from lung adenocarcinoma patients with lytic bone metastasis was significantly lower compared to that in patients with metastases in other organs. The potential roles of miR­139­5p as a biomarker and treatment target in monitoring and controlling bone metastasis in lung cancer patients are worthy of being further explored.

The investigation for potential modifier genes in patients with neurofibromatosis type 1 based on next-generation sequencing.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is a common Mendelian multi-system disorder that is characterized by café-au-lait spots (CLS), axillary freckling, optic glioma and plexiform neurofibroma. Various mutations of the NF1 gene are widely accepted to be the main cause of this disease, while whether there are still certain other modifier genes that could influence the phenotypes of NF1 is our concern. PATIENTS AND METHODS: One proband and his father are involved, who are characterized by plexiform neurofibroma and cutaneous neurofibroma, respectively. Enhanced Computed tomography (CT) and Positron emission tomography-CT (PET-CT) were taken to collect the radiographic data, and the specimens of this neurofibroma as well as the blood samples from the father and son were sent for panel mutation screening of 295 tumor-related genes based on next-generation screening. Furthermore, the NF1 gene mutations were referred with Canis lupus familiaris, Rattus norvegicus, Gallus gallus, Danio rerio, and Drosophila melanogaster NF1 sequencing for evolutionary conservativeness and then analyzed in Condel databases for pathogenicity prediction. RESULTS: The radiography indicated that the benign plexiform neurofibroma only occurred in the son. Also, TP53, FANCA, BCL6, PIK3C2G, RNF43, FGFR4, FLT3, ERBB2, PAK7, NSD1, MEN1 and TSC1 were uniquely found mutated in the son, which could be candidates as new modifier genes; besides, RNF43 was also mutated in public neurofibroma seuquencing data. By KEGG pathway annotation, phosphoinositide-3-kinase-Akt pathway was altered in both the public plexiform neurofibroma sample and in our proband patient. CONCLUSION: This study reexamined the background germline mutations and suggested their potential value as modifier genes that may influence the phenotype heterogenity.

Clinicopathological and genetic characteristics of pulmonary large cell carcinoma under 2015 WHO classification: a pilot study.

Pulmonary large cell carcinoma (LCC) was re-defined under the 2015 WHO classification criteria. However, the clinicopathological features and genetic mutation statuses of Chinese LCC patients based on the new classification have rarely been investigated. Twenty-four Chinese surgically resected LCC patients previously diagnosed under the 2004 WHO criteria were re-classified under the 2015 WHO criteria. Genetic analysis was performed using next-generation sequencing of 46 cancer-related genes. The correlation of clinicopathological and genetic data was further analyzed. Eight patients were re-defined as LCCs, and 16 patients were defined as non-LCCs under the refined criteria. All LCC patients were male, and 7 patients were smokers. No significant differences in age, gender, smoking status, primary site, TNM staging and overall survival were observed between the LCC and non-LCC patients under the refined criteria. Four of the 8 LCC patients presented TP53 mutations, and no somatic mutations were detected in the other 4 LCCs under the refined criteria. For the 16 non-LCCs, not only TP53 and KRAS but also EGFR, KIT, PIK3CA, PTEN, IDH1, APC, ATM and BRAF mutations were also observed. In addition, LCCs without TP53 mutations did not present any gene mutations under the 2004 or 2015 WHO criteria. Importantly, the patients with TP53 mutation exhibited a trend with a worse survival outcome at the time of follow-up. The new WHO diagnosis criteria have superior performance in precise molecular classification for LCC patients.

Primary pulmonary malignant fibrous histiocytoma: case report and literature review.

Malignant fibrous histiocytoma (MFH) is an aggressive soft tissue sarcoma known to occur in various organs. Primary MFH arising in the lung is quite rare. Herein we report a case of a 61-year-old male with primary pulmonary MFH and explore the underlying molecular mechanisms by next-generation sequencing (NGS). Five gene mutations in TSC2, ARID1B, CDK8, KDM5C and CASP8 were detected, and the mTOR inhibitor might be an effective treatment for this patient. In addition, we reviewed the scientific literature of approximately 23 primary pulmonary MFH case reports since 1990 and summarized the clinical features and prognosis of this rare pulmonary malignant tumor.

Concurrent epidermal growth factor receptor T790M secondary mutation and epithelial-mesenchymal transition in a lung adenocarcinoma patient with EGFR-TKI drug resistance.

Almost all epidermal growth factor receptor (EGFR)-mutant lung cancers develop resistance to EGFR-tyrosine kinase inhibitors. Several mechanisms for this acquired resistance have been identified, including development of an EGFR T790M mutation, MET amplification, hepatocyte growth factor overexpression, loss of phosphatase and tensin homolog expression, epithelial-mesenchymal transition, and transformation to small cell lung cancer. Herein, we report a case of a lung cancer patient with EGFR exon 19 deletion who was resistant to EGFR-tyrosine kinase inhibitor treatment during disease progression. Using histological and gene sequencing analysis, we observed that the primary adenocarcinoma acquired T790M mutation in EGFR exon 20, and a secondary sarcomatoid carcinoma developed in the vicinity. Assessment of E-cadherin and Vimentin expression confirmed that the sarcomatoid carcinoma had undergone an epithelial-mesenchymal transition. Therefore, it is important to perform a tissue re-biopsy after the development of resistance to identify the best treatment options. Surgical resection might be a better "salvage" treatment in cases of oligometastatic progression.