Renwang Liu

Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma: Known compounds as agents for LUAD

This study compared tumor‐related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment.

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.

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.

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.

Examined lymph node count in non-small-cell lung cancer: will it be a decision making approach in treatment of NSCLC?

Surgical therapy, which accurate staging and pathological diagnosis relay on, is still irreplaceable in the treatment strategy of lung cancer, especially for the early stage non-small-cell lung cancer (NSCLC) (1). Besides resection of tumors, many prognostic factors, including nodal status, histology, and tumor size, can be provided through surgical procedure. Nodal status, as one of the most important factors in the staging definition and adjuvant chemotherapy selection, has always been playing a significant role in the heath care of lung cancer patients (2). However, differing from gastrointestinal and breast cancer, the recommendation of lymph node (LN) dissection or examinations from NCCN is in the qualitative level and the studies focus on the examined lymph nodes (ELNs) is still insufficient in lung cancer (1,3,4). Thus, Liang et al. investigated the effect of ELNs in the staging and prognosis of NSCLC in a real-world retrospective analysis, which tried to provide a reliable evidence of LN management in the quantitative level for NSCLC patients (5).

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.

18F-FDG-PET-CT with Little Value in Different Diagnosis between Pulmonary Malignancy and Amyloidosis

Pulmonary amyloidosis is rare and is often misdiagnosed due a lack of general awareness of the condition. The role of PET-CT in the differential diagnosis between pulmonary amyloidosis and lung malignant tumors is still unclear. Herein, we describe a 61-year-old Chinese woman who presented with a right lower lobe pulmonary nodule, and right hilar and mediastinal lymph nodes shadows. On PET-CT examination, the patient was found to have right lower lung malignant lesions with multiple right hilar and mediastinal lymph node metastases. She was diagnosed with nephrotic syndrome with a history of pathologic type of amyloidosis over the previous two months. After performing right thoracotomy, a histopathologic diagnosis of pulmonary amyloidosis was made. The patient has done well postoperatively, showing no local recurrence in the lung or deterioration of her condition in a 12- month follow-up period. The pathology of nephrotic syndrome in patients with amyloidosis led to the diagnosis of systemic amyloidosis being made in this patient. From this case, combined with the domestic and international literature, we conclude that PET-CT is of little value for the different diagnosis between pulmonary amyloidosis and lung malignant tumors.