Pathological Type Of Lung Cancer Research Articles

Study on the relationship between the pathological type of lung cancer caused by coke oven discharge and the contact type and exposure time

Objective: To study the pathological types of lung cancer caused by coke oven emissions and analyze the correlation between different exposure levels. Methods: In October 2020, the relevant data of 86 confirmed cases of lung cancer caused by coke oven emissions (including basic information of patients, relevant occupational exposure and clinical data) were collected, The workers were grouped according to the different COEs concentrations in their posts: workers in auxiliary posts were taken as the low exposure group (11 persons) , The workers at coke side and furnace bottom are the medium exposure group (14 persons) , and the workers at furnace top are the high exposure group (61 persons) , and the correlation between pathological types of lung cancer and different exposure levels was analyzed. Results: There was no significant difference in age and length of service among the groups (P>0.05) ; The number of lung cancer cases and pathological types among workers in each group were statistically significant (P=0.044) . After adjusting for interference factors, the number of undifferentiated cancers (mainly small cell lung cancer) increased with the increase of exposure level, with a statistically significant difference (P=0.001) . The incidence of lung cancer increased gradually with the length of service, and the incidence rate of lung cancer among workers of different working ages was statistically significant (P<0.05) . Conclusion: Undifferentiated small cell carcinoma is the most common pathological type of lung cancer caused by coke oven emissions, and the incidence of lung cancer tends to increase with the length of service.

MET alterations in advanced pulmonary sarcomatoid carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subset of NSCLC that accounts for about 0.5-1% of all primary lung carcinoma, and its malignant biological behavior is more aggressive than other pathological types of lung cancer. Recent studies have reported a variety of gene mutations associated with the occurrence, development and treatment of PSC, especially the mesenchymal-epithelial transition (MET) proto-oncogene alterations, including the exon 14 (METex14) skipping mutations as well as the amplification and overexpression of MET gene, which are associated with molecularly targeted therapy for PSC. METex14 skipping mutation is the most common and well-studied mutation type, occurring in about 22-31.8% of PSC patients, while the prevalence of MET amplification is reported as 4.8-13.6% and MET ovexpression is about 20.2%. Molecular pathology tests, including IHC and NGS, are valuable in determining the prognosis of patients with PSC and helping to determine the treatment. The existing clinical data have confirmed the efficacy of MET-TKI in PSC patients with MET alteration, among which the clinical study of Savolitinib has enrolled the largest proportion of PSC patients and achieved relatively good efficacy, but more clinical researches are still needed. The multi-disciplinary team may maximize the optimal treatment options for patients with the advanced PSC.

High expression of E2F transcription factors 7: An independent predictor of poor prognosis in patients with lung adenocarcinoma.

Adenocarcinoma is the most common pathological type of lung cancer. The E2F7 transcription factor has been confirmed to be related to the occurrence and development of a variety of solid tumors, but the relationship with the prognosis of lung cancer is still unclear. Therefore, we conducted this study to explore the prognostic value of E2F7 for lung adenocarcinoma (LUAD) patients.In this study, we analyzed samples from the Cancer Genome Atlas (TCGA) to study the correlation between the expression of E2F7 and clinical features, the difference in expression between tumors and normal tissues, the prognostic and diagnostic value, and Enrichment analysis of related genes. All statistical analysis uses R statistical software (version 3.6.3).The result shows that the expression level of E2F7 in LUAD was significantly higher than that of normal lung tissue (P = 1e-34). High expression of E2F7 was significantly correlated with gender (P = .034), pathologic stage (P = .046) and M stage (P = .025). Multivariate Cox analysis confirmed that E2F7 is an independent risk factor for OS in LUAD patients (P = .027). Genes related to cell cycle checkpoints, DNA damage telomere stress-induced senescence, DNA methylation, chromosome maintenance and mitotic prophase showed differential enrichment in the E2F7 high expression group.In short, high expression of E2F7 is an independent risk factor for OS in LUAD patients and has a high diagnostic value.

Potential Implications of the Lung Microbiota in Patients with Chronic Obstruction Pulmonary Disease and Non-Small Cell Lung Cancer.

Recently, chronic obstructive pulmonary disease (COPD) has been considered as a common risk factor of non-small cell lung cancer (NSCLC). However, very few studies have been conducted on the effects of COPD on the lung microbiota in patients with NSCLC. To identify the lung microbiota in patients with COPD and NSCLC (CN), the microbiome of the induced sputa of 90 patients was analyzed using 16S rDNA sequencing. The results showed no significant differences in the bacterial diversities of induced sputa among patients with COPD, NSCLC, and CN and no intrinsic differences among patients with different pathological types of lung cancer. After surgical operation, the diversities of the induced sputa in patients with CN significantly decreased. More remarkably, both the microbial community phenotypes and the components of the induced sputa in patients with CN obviously differed from those in patients with COPD or NSCLC. The relative abundances of Streptococcus, Veillonella, Moraxella, and Actinomyces significantly decreased, but those of Neisseria and Acinetobacter significantly increased in patients with CN compared with those in patients with COPD or NSCLC alone, resulting in increased Gram-negative microbiota and, therefore, in potential pathogenicity and stress tolerance, as well as in enhancement of microbial glycolipid metabolism, amino acid metabolism, and oxidative stress. Although COPD did not affect the number of pulmonary flora species in patients with NSCLC, these significant alterations in the microbial populations, phenotypes, and functions of induced sputa due to COPD would contribute to inflammation-derived cancer progression in patients with CN.

AA amyloidosis associated with cancers.

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.

Abnormal Gene Expression Regulation Mechanism of Myeloid Cell Nuclear Differentiation Antigen in Lung Adenocarcinoma.

Simple SummaryLung adenocarcinoma is the main pathological type of lung cancer with a very low 5-year survival rate. In the present study, through analyzing the mRNA, miRNA, and DNA methylation sequencing data from TCGA, combined with the downloaded clinical data, we accidentally found that both methylation and gene expression of some genes were up-regulated or down-regulated, which is in contradiction with our general understanding. To probe the mechanism, we selected MNDA associated with lung cancer prognosis for further analysis. The results showed that the imbalance of methylase and demethylase resulted in the demethylation of MNDA. Moreover, the expression of SPI1, the main transcription factor of MNDA, was down-regulated, while the two miRNAs hsa-miR-33a-5p and hsa-miR-33b-5p, which directly targeted MNDA, were up-regulated, thus inhibiting the expression of MNDA. In conclusion, the abnormal expression of MNDA in lung cancer is the result of the combined effects of transcriptional and post-transcriptional regulation.Lung adenocarcinoma (LA) is the main pathological type of lung cancer with a very low 5-year survival rate. In the present study, after downloading the mRNA, miRNA, and DNA methylation sequencing data from TCGA, combined with the downloaded clinical data, comparative analysis, prognostic analysis, GO and KEGG analysis, GSEA analysis, methylation analysis, transcriptional regulation and post-transcriptional regulation were performed. We found that both methylation and gene expression of MNDA in LA were down-regulated, while high expression of MNDA was associated with good overall survival in LA. To probe the mechanism, further analysis showed that SPI1 was the main transcription factor of MNDA, but it was also down-regulated in LA. At the same time, the expression of eight target miRNAs of MNDA was significantly up-regulated, and the expression of hsa-miR-33a-5p and hsa-miR-33b-5p were verified to directly target MNDA. In conclusion, the abnormal expression of MNDA in LA is the result of the combined effects of transcriptional and post-transcriptional regulation.

Cuproptosis-Related Gene - SLC31A1, FDX1 and ATP7B - Polymorphisms are Associated with Risk of Lung Cancer.

BackgroundCuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in cuproptosis-related genes and lung cancer risk.MethodsSix SNPs of the SLC31A1, FDX1 and ATP7B genes were genotyped in a case–control cohort including 650 lung cancer cases and 650 controls using the MassARRAY platform.ResultsThe minor alleles of SLC31A1-rs10981694 and FDX1-rs10488764 were associated with an increased risk of lung cancer (rs10981694: OR=1.455, 95% CI: 1.201–1.763, p<0.001; rs10488764: OR=1.483, 95% CI: 1.244–1.768, p<0.001). In contrast, the minor alleles of rs9535826 and rs9535828 in ATP7B were related to a decreased risk of the disease (rs9535826: OR=0.714, 95% CI: 0.608–0.838 p<0.001; rs9535828: OR=0.679, 95% CI: 0.579–0.796, p<0.001). The frequencies of rs10981694-TG/GG and rs10488764-GA/AA genotypes were significantly higher in lung cancer cases than that in controls, making them risk genotypes for the disease (p < 0.001); while the rs9535826-TG/GG and rs9535828-GA/AA genotypes were protective genotypes and associated with a reduced risk of the disease (p<0.001). Genetic model evaluation revealed that SLC31A1-rs10981694 and FDX1-rs10488764 were associated with a growing risk of lung cancer in dominant, recessive and log-additive models (p<0.001). Moreover, rs9535826 and rs9535828 in ATP7B were related to a declining risk of the disease in three genetic models (p<0.001). In addition, stratification analysis showed that FDX1-rs10488764 was risk variant for lung cancer in both smokers and nonsmokers, and was associated with risk of each pathological type of lung cancer (p<0.008).ConclusionThe results shed new light on the correlation between cuproptosis-related genes and risk of lung cancer.

Research Progress of Antibody-drug Conjugates in Advanced Non-small Cell Lung Cancer

肺癌是全球发病率和死亡率最高的恶性肿瘤之一，非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌重要的病理类型之一，且晚期患者预后较差，内科治疗仍是其主要治疗手段。抗体偶联药物（antibody-drug conjugates, ADCs）是一类非常有潜力的新型抗肿瘤药物，由单克隆抗体和小分子细胞毒药物通过连接子偶联而成，在肺癌等实体瘤中应用前景广阔。本文对现阶段ADCs在晚期NSCLC中的作用机制和研究进展进行综述。

Correlation and clinical significance of methyltransferases SETDB1 and SPG20 methylation in lung adenocarcinoma

Objective: The incidence of primary lung adenocarcinoma is increasing year by year in worldwide, and it has surpassed squamous cell carcinoma to become the most common pathological type of lung cancer. Advances in medical technology have made the overall survival rate of lung cancer patients improve, but it is still very low. In the study, we investigated the methyltransferase SETDB1 expression and the methylation level of SPG20, and analyzed the correlation and its clinical significance in the pathogenesis of lung adenocarcinoma. Methods: 60 lung adenocarcinoma and normal lung tissues were selected.The expression of SPG20 and SETDB1 mRNA was examined by RT-qPCR; Protein expression of SPG20 and SETDB1 was determined by immunohistochemistry(SP) and immune protein imprinting(Western blot);Methylation level of SPG20 gene was determined by pyrosequencing. Correlation between SETDB1 and SPG20 methylation levels and both and clinical case characteristics was analysed by statistics. Western blot detection of SETDB1 and SPG20 protein expression in lung adenocarcinoma cells and normal bronchial mucosal epithelial cells.The small interfering RNA of SETDB1 was transfected into lung adenocarcinoma A549 cells by liposome-mediated method, the mRNA and protein expression levels of SETDB1 were detected by RT-qPCR and Wesrern blot, and the methylation level of SPG20 gene was detected by pyrosequencing. Results:Relative expression of SPG20 mRNA was significantly lower in lung adenocarcinoma tissue than in normal lung tissue, while relative SETDB1 mRNA expression was higher in cancer tissue than in normal lung tissue. SETDB1 protein expression was significantly higher in lung adenocarcinoma tissue than in normal lung tissue, while SPG20 protein showed lower expression in cancer tissue than in normal lung tissue. The methylation rate of the SPG20 gene was significantly higher in cancerous tissues than in normal lung tissue, the difference was statistically significant. SPG20 methylation in cancer tissues showed a correlation with SETDB1 and showed a positive correlation; SPG20 methylation and SETDB1 are closely related with TNM stage, tissue differentiation, and lymph node metastasis in lung adenocarcinoma. The vitro experiments showed that SETDB1 was highly expressed, while SPG20 was lowIn lung adenocarcinoma cells, SETDB1 was low and SPG20 was high in normal bronchial epithelial cells. RNA interference with SETDB1 could significantly reduce the mRNA and protein expression of SETDB1 in A549 cells, the methylation rate of SPG20 gene was significantly decreased, and the protein expression was increased. Conclusion:There is a significant correlation between methyltransferases SETDB1 and SPG20 methylation in lung adenocarcinoma, and high SETDB1 expression may be the upstream molecule of SPG20 methylation, working together in promoting the occurrence and development of lung adenocarcinoma.

18F]AlF-NOTA-FAPI-04 PET/CT uptake in metastatic lesions on PET/CT imaging might distinguish different pathological types of lung cancer

PurposeHeterogeneity is found in the tumor microenvironment among different pathological types of tumors. Radionuclide-labeled fibroblast-activation-protein inhibitor (FAPI), as an important tracer for non-invasive imaging of the tumor microenvironment, can be used to evaluate the expression of FAP in cancer-associated fibroblasts, macrophages, and tumor cells. Our aim was to explore the ability of [18F]AlF-NOTA-FAPI-04 positron emission tomography (PET)/computed tomography (CT) to distinguish different types of lung cancer by evaluating the uptake of this tracer in primary and metastatic lesions.MethodsWe prospectively enrolled 61 patients with histopathologically proven primary lung cancer with metastases. PET/CT scanning was performed before any antitumor therapy and 1 h after injection of 235.10 ± 3.89 MBq of [18F]AlF-NOTA-FAPI-04. Maximum standard uptake values (SUVmax) were calculated for comparison among primary and metastatic lesions. Immunohistochemical staining for FAP was performed on tumor specimens.ResultsSixty-one patients with adenocarcinoma (ADC, n = 30), squamous cell carcinoma (SCC, n = 17), and small cell lung cancer (SCLC, n = 14) were enrolled in this study, and 61 primary tumors and 199 metastases were evaluated. No difference in [18F]AlF-NOTA-FAPI-04 uptake was observed among primary ADC, SCC, and SCLC tumors (P = 0.198). Additionally, no difference in uptake was found between primary and metastatic lesions of lung cancer with the same pathological type (P > 0.05). However, uptake did differ among metastases of differing pathological types (P < 0.001). The SUVmax of metastatic lymph nodes was highest for SCC, followed by ADC and then SCLC (P < 0.001). The SUVmax of bone metastases also was highest for SCC, followed by ADC and SCLC (P < 0.05), but no difference was observed between ADC and SCLC. The SUVmax of metastases in other organs was higher in SCC cases than in ADC cases but did not differ between SCC and SCLC or ADC and SCLC. Bone metastases exhibited higher uptake than those of lymph nodes and other organs in SCC and ADC (P < 0.05) but not in SCLC. Positive correlations were found between FAPI uptake and FAP expression in surgical plus biopsy specimens (r = 0.439, P = 0.012) and surgical specimens (r = 0.938, P = 0.005).Conclusion[18F]AlF-NOTA-FAPI-04 PET/CT imaging revealed differences in FAP expression in metastases of lung cancer, with the highest expression specifically in bone metastases, and thus, may be valuable for distinguishing different pathological types of lung cancer.

Exploration of Lung Cancer-Related Genetic Factors via Mendelian Randomization Method Based on Genomic and Transcriptomic Summarized Data.

Lung carcinoma is one of the most deadly malignant tumors in mankind. With the rising incidence of lung cancer, searching for the high effective cures become more and more imperative. There has been sufficient research evidence that living habits and situations such as smoking and air pollution are associated with an increased risk of lung cancer. Simultaneously, the influence of individual genetic susceptibility on lung carcinoma morbidity has been confirmed, and a growing body of evidence has been accumulated on the relationship between various risk factors and the risk of different pathological types of lung cancer. Additionally, the analyses from many large-scale cancer registries have shown a degree of familial aggregation of lung cancer. To explore lung cancer-related genetic factors, Genome-Wide Association Studies (GWAS) have been used to identify several lung cancer susceptibility sites and have been widely validated. However, the biological mechanism behind the impact of these site mutations on lung cancer remains unclear. Therefore, this study applied the Summary data-based Mendelian Randomization (SMR) model through the integration of two GWAS datasets and four expression Quantitative Trait Loci (eQTL) datasets to identify susceptibility genes. Using this strategy, we found ten of Single Nucleotide Polymorphisms (SNPs) sites that affect the occurrence and development of lung tumors by regulating the expression of seven genes. Further analysis of the signaling pathway about these genes not only provides important clues to explain the pathogenesis of lung cancer but also has critical significance for the diagnosis and treatment of lung cancer.

Correlation between apparent diffusion coefficient and Ki-67 in different pathological types of lung cancer.

BackgroundComputed tomography (CT) is common and valuable non-invasive method to evaluate proliferative activity in lung cancer; however, magnetic resonance (MR) is rarely used in lung cancer. To evaluate whether there were different expression levels of Ki-67 in different pathological types of lung cancer and the correlation between Ki-67 index and apparent diffusion coefficient (ADC) value.MethodsThe clinical and pathological data of 165 patients with lung cancer confirmed by needle biopsy or surgery were retrospectively evaluated, among whom 54 underwent MR examination. The level of Ki-67 was tested using the international standard IHC 2-step method. Kruskal-Wallis H test was used to compare the different expression level of Ki-67 index of adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, and the least significant difference (LSD) method was used for pair-group comparison. Spearman correlation coefficient was used to analyze the correlation between Ki-67 index and ADC value. All statistical tests were bilateral, and P<0.05 was considered statistically significant.ResultsThe median of Ki-67 index in adenocarcinoma, squamous cell carcinoma, and small cell carcinoma were 20 (10, 30), 40 (40, 60), and 70 (60, 80), respectively. There was a statistical difference in the expression level of Ki-67 index in the 3 different pathological types of lung cancer (H=103.762, P=0.000). In 54 cases of lung cancer with MR examination, there was a significant negative correlation between average ADC value and expression level of Ki-67 index (r=−0.506, P=0.000), while there was no correlation between ADC value and Ki-67 index in distinguishing different pathological types of lung cancer.ConclusionsThe expression level of Ki-67 index was different among different pathological types of lung cancer. The ADC value is correlated with Ki-67 index in lung cancer, which can be used to evaluate the proliferative activity of lung cancer.

Advances in Biomarkers for Immunotherapy of Non-small Cell Lung Cancer

肺癌是全球死亡率最高的恶性肿瘤，非小细胞肺癌（non-small cell lung cancer, NSCLC）是其最常见的病理类型。近年来，免疫治疗给NSCLC的治疗带来划时代的变革，尤其是针对程序性死亡受体1（programmed cell death 1, PD-1）/程序性死亡配体1（programmed cell death ligand 1, PD-L1）的免疫检查点抑制剂（immune checkpoint inhibitors, ICIs），目前已被批准用于转移性NSCLC或部分局部晚期NSCLC患者的一线治疗和二线治疗。然而，仅15%-30%晚期NSCLC患者可以从免疫治疗中获得持续缓解和长期生存，如何探寻良好的生物标志物来有效地预测免疫治疗的疗效是当前面临的巨大挑战之一。本文对NSCLC免疫治疗疗效预测生物标志物的研究进展进行综述。

Identification and validation of an individualized prognostic signature of lung squamous cell carcinoma based on ferroptosis-related genes.

BackgroundLung squamous cell carcinoma (LUSC), one of the main pathological types of lung cancer, has led to consequential socioeconomic burden. Ferroptosis is an iron‐dependent form of cell death process with potentials for therapeutic target in various kinds of tumors. However, whether ferroptosis‐related genes (FRGs) are associated with the prognosis of LUSC patients is still unclear. The aim of this study was to establish a FRGs‐based signature which could stratify patients with LUSC.MethodsThe RNA sequencing profiles and corresponding clinical data of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) dataset. A FRG‐based signature was developed using the TCGA‐LUSC cohort and validated in the GEO cohort. Gene set enrichment analysis (GSEA) and analysis of immune cell characteristics were conducted to assess the relationship between FRGs and biological function or immune status. A nomogram based on selected clinical factors and the risk scores which were generated from the FRG‐based signature was developed using the TCGA cohort and validated in the GEO cohort.ResultsA set of 16 FRGs, significantly associated with overall survival (OS) in the TCGA cohort, was identified and could classify LUSC patients into two risk groups. Kaplan–Meier analysis illustrated that the survival rate of the high‐risk group was significantly lower than the low‐risk group. Assessment and external validation of the signature showed that the survival predictive performance of this signature was adequate. Additionally, multiple pathways and functions were enriched through GSEA and the analysis of immune cell characteristics showed significantly different abundances of immune cells among the two risk groups. Finally, a nomogram integrating the FRG‐based signature and selected clinical factors was also developed and assessed in both the TCGA and GEO cohort.ConclusionThis study indicated the association between the FRGs and prognosis of patients with LUSC. Targeting ferroptosis may serve as a novel potential therapeutic alternative for LUSC.

Genomic comparison between cerebrospinal fluid and primary tumor revealed the genetic events associated with brain metastasis in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.

Research Progress of the Clinical Application of Small Cell Lung Cancer Related Tumor Markers and Biochemical Indicators

With continual advances in medicine, more studies on early diagnosis, therapeutic evaluation, and prognosis of lung cancer have emerged in recent years, particularly in regard to small cell lung cancer (SCLC), which is a pathological type of lung cancer with the highest grade. In the era of medical treatment scarcity, early diagnosis of SCLC, evaluation of treatment effect, recurrence factors, and prognosis are important to treat patients with SCLC, prolong their survival, and improve their life quality. The research on the changes of serum tumor markers and biochemical indicators in the early diagnosis and treatment of SCLC has gradually become a hot topic. Therefore, this article reviews the research progress of serum tumor markers and biochemical indicators of SCLC.

Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway.

Lung cancer is the most common malignant tumor type and it is associated with poor prognosis. The identification of potential biomarkers is of great significance for the early diagnosis and treatment of lung cancer. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The present study aimed to investigate the mechanism via which thyroid hormone receptor-interacting protein 13 (TRIP13) participates in the malignant progression of NSCLC. Immunohistochemistry, reverse transcription-quantitative PCR and western blotting were used to assess the expression level of TRIP13. According to The Cancer Genome Atlas database, TRIP13 was upregulated in NSCLC tissues compared with adjacent normal tissues. Moreover, TRIP13 knockdown increased apoptosis, induced cell cycle arrest in the S phase and inhibited the proliferation, invasion and migration of H1299 cells in vitro. Furthermore, TRIP13 upregulation was closely associated with tumor metastasis via epithelial-mesenchymal transformation. In conclusion, TRIP13 could promote the malignant progression of lung cancer, and TRIP13 may be a potential biomarker for the early diagnosis and treatment of NSCLC.

Identification of Prognostic Signature and Gliclazide as Candidate Drugs in Lung Adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, with high incidence and mortality. To improve the curative effect and prolong the survival of patients, it is necessary to find new biomarkers to accurately predict the prognosis of patients and explore new strategy to treat high-risk LUAD.MethodsA comprehensive genome-wide profiling analysis was conducted using a retrospective pool of LUAD patient data from the previous datasets of Gene Expression Omnibus (GEO) including GSE18842, GSE19188, GSE40791 and GSE50081 and The Cancer Genome Atlas (TCGA). Differential gene analysis and Cox proportional hazard model were used to identify differentially expressed genes with survival significance as candidate prognostic genes. The Kaplan–Meier with log-rank test was used to assess survival difference. A risk score model was developed and validated using TCGA-LUAD and GSE50081. Additionally, The Connectivity Map (CMAP) was used to predict drugs for the treatment of LUAD. The anti-cancer effect and mechanism of its candidate drugs were studied in LUAD cell lines.ResultsWe identified a 5-gene signature (KIF20A, KLF4, KRT6A, LIFR and RGS13). Risk Score (RS) based on 5-gene signature was significantly associated with overall survival (OS). Nomogram combining RS with clinical pathology parameters could potently predict the prognosis of patients with LUAD. Moreover, gliclazide was identified as a candidate drug for the treatment of high-RS LUAD. Finally, gliclazide was shown to induce cell cycle arrest and apoptosis in LUAD cells possibly by targeting CCNB1, CCNB2, CDK1 and AURKA.ConclusionThis study identified a 5-gene signature that can predict the prognosis of patients with LUAD, and Gliclazide as a potential therapeutic drug for LUAD. It provides a new direction for the prognosis and treatment of patients with LUAD.

Human Endogenous Retrovirus-H Long Terminal Repeat- Associating Protein 2 (HHLA2) is a Novel Immune Checkpoint Protein in Lung Cancer which Predicts Survival.

Background:Lung cancer is one of the most frequently diagnosed malignancies. Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a recently discovered ligand of the B7 family. Blocking this immune checkpoint has become an important treatment option for lung cancer. Methods:The study includes 62 biopsy specimens either bronchoscopic or CT-guided biopsies diagnosed as lung cancer in Hospitals of Faculty of Medicine, Mansoura University, Egypt during the period from 2016 to 2020. Immunohistochemical Staining for HHLA2 and EGFR was performed. HHLA2 expression was assessed in different pathological types of lung Cancer, and it was correlated with other clinicopathologic parameters and patient prognosis. Results:We found a significant association between HHLA2 expression and metastasis. About 83% of patients presented with metastasis showed positive expression of HHLA2 compared to 44.4% in patients with no metastasis (p=0.02). Also, results show significant mild positive correlation between expression of HHLA2 and EGFR markers (p=0.045). The mean OS time in cases with positive HHLA2 expression was nearly half that of patients with negative expression of the markers. However, this difference was not statistically significant. But, PFS of patients was significantly lower among the group with positive expression of HHLA2 compared to the group with negative expression of HHLA2 (p= 0.01). Conclusions:This study reports that recently discovered, HHLA2 is over expressed in lung cancer associating with higher stage. It is also correlated with EGFR overexpression. HHLA2 could serve as a predictor of progression and distant metastasis. Also, it has potential to be effective immune target in lung cancer immunotherapy such as checkpoint blockade and antibody-drug conjugate treatment.

Low-dose spectral CT perfusion imaging of lung cancer quantitative analysis in different pathological subtypes.

BackgroundTo explore the value of the quantitative parameters of low-dose computed tomography (CT) perfusion in the diagnosis of lung cancers of different pathological types.MethodsEighty-five patients with lung cancer confirmed by pathology underwent enhanced spectral CT imaging with a General Electric (GE) Revolution Xtream CT scanner, including 7 patients with lung squamous cell carcinoma, 8 patients with small cell carcinoma, 67 patients with lung adenocarcinoma, and 3 patients with other pathologies. The low-dose CT perfusion parameters [blood flow (BF), blood volume (BV), time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), positive enhancement integral (PEI), time to peak (TTP) and time to maximum (Tmax)] were calculated and compared among the first three groups. One-way analysis of variance (ANOVA) or the Kruskal-Wallis test was used to compare the quantitative parameters among the three groups, and the Bonferroni method was used to correct for multiple comparisons.ResultsAmong the quantitative parameters, MSI was significantly different among the three lung cancers (adenocarcinoma vs. squamous cell carcinoma vs. small cell carcinoma: 11.37±8.74 vs. 2.35±0.88 vs. 1.40±0.26, respectively; P=0.016). The MSI of lung adenocarcinoma was lower than that of non-adenocarcinoma (P=0.001), and the MSI of small cell carcinoma was lower than that of non-small cell carcinoma (P=0.014). There were no significant differences in the other parameters among these three groups (P>0.05).ConclusionsLow-dose CT perfusion parameters may have a certain value in classifying the pathological type of lung cancer.