Higher maternal embryonic leucine zipper kinase mRNA expression level is a poor prognostic factor in non-small-cell lung carcinoma patients

2019 ◽  
Vol 13 (16) ◽  
pp. 1349-1361
Author(s):  
Xuefeng Zang ◽  
Chunyan Qian ◽  
Ye Ruan ◽  
Junwen Xie ◽  
Ting Luo ◽  
...  

Aim: To elucidate potential prognostic significance of MELK mRNA expression in non-small-cell lung carcinoma patients. Methods: A loop algorithm based on R software was used to select genes with the best prognostic value. Mantel–Haenszel method and functional enrichment analysis were used to perform this analysis. Results: MELK mRNA expression level in tumor tissue is significantly higher than that in normal/benign tissue (p < 0.001), and gradually increases from stage I to IV (lung adenocarcinoma: p = 0.011; lung squamous cell carcinoma: p = 0.002), and is negatively correlated with prognosis in lung adenocarcinoma patients (HR: 2.025 in univariate analysis; HR: 2.162 in multivariate analysis). However, it does not show a significant correlation in lung squamous cell carcinoma patients. Conclusion: MELK is a poor biomarker for non-small-cell lung carcinoma patients and can potentially be used as a therapeutic target.

Author(s):  
Ran Su ◽  
Jiahang Zhang ◽  
Xiaofeng Liu ◽  
Leyi Wei

Abstract Motivation Non-small-cell lung carcinoma (NSCLC) mainly consists of two subtypes: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). It has been reported that the genetic and epigenetic profiles vary strikingly between LUAD and LUSC in the process of tumorigenesis and development. Efficient and precise treatment can be made if subtypes can be identified correctly. Identification of discriminative expression signatures has been explored recently to aid the classification of NSCLC subtypes. Results In this study, we designed a classification model integrating both mRNA and long non-coding RNA (lncRNA) expression data to effectively classify the subtypes of NSCLC. A gene selection algorithm, named WGRFE, was proposed to identify the most discriminative gene signatures within the recursive feature elimination (RFE) framework. GeneRank scores considering both expression level and correlation, together with the importance generated by classifiers were all taken into account to improve the selection performance. Moreover, a module-based initial filtering of the genes was performed to reduce the computation cost of RFE. We validated the proposed algorithm on The Cancer Genome Atlas (TCGA) dataset. The results demonstrate that the developed approach identified a small number of expression signatures for accurate subtype classification and particularly, we here for the first time show the potential role of LncRNA in building computational NSCLC subtype classification models. Availability and implementation The R implementation for the proposed approach is available at https://github.com/RanSuLab/NSCLC-subtype-classification.


2022 ◽  
Vol 9 (01) ◽  
pp. 5800-5907
Author(s):  
Dr. Savita Singh ◽  
Dr. Kuldeep Singh

BACKGROUND :- Lung cancer is the leading cause of cancer-related mortality over word wide, Although the pathological diagnosis of lung carcinoma is limited as only small specimen available for diagnosis.the availability of targeted therapies has created a need for precise subtyping of non-small cell lung carcinoma . Several recent studies have demonstrated that the use of  Immunohistochemical markers can be helpful in differentiating lung squamous cell carcinoma (LSCC) from lung adenocarcinoma (LAC) not on surgically resected material but also on small biopsy samples and cytology. AIM  (1)          To classify the non small cell lung carcinoma  into major categories like squamous cell carcinoma (LSCC) and adenocarcinoma (LAC) and other categories by applying  immunohistochemicalmarker like  p40 (truncated p63) and Napsin A    (2)     To analyse the sensitivity and specificity of p40 and Napsin A in light of histomorphology and/or other relevant immunohistochemical markers available, using appropriate statistical tests. Material and methods:- This  study was a one and half year (18 months) prospective study from Jan 2017 to June 2018, conducted in department of pathology on patients attending the outpatient and inpatient department of TB and respiratory disease, a total of  210 bronchoscopic guided biopsies / transthoracic (CT/MRI /guided) small tissue biopsies from the patients suspected of lung malignancy were incorporated in the study. 20 corresponding resection specimens (wedge resection and lobectomy) were also included in the study for correlation of morphology and immunohistochemical findings on small biopsies. RESULTS:-In our study IHC for both p40 and napsin –A aided in subtyping of  71.9% cases of non small cell lung carcinoma and this diagnostic accuracy was found to be statistically significant with p-value < 0.05.,on statistical analysis  we found that napsin-A had a sensitivity of  90% and specificity of 80%. Also, positive predictive value and negative predictive value were seen to be 88.0% and 81.8% respectively.    


2019 ◽  
Vol 7 ◽  
pp. 2050313X1988159
Author(s):  
Roxana Mititelu ◽  
Mathieu Powell

Acrokeratosis paraneoplastica (Bazex syndrome) is a paraneoplastic syndrome frequently associated with squamous cell carcinoma of the aerodigestive tract. We present a case of acrokeratosis paraneoplastica associated with non-small-cell lung carcinoma, which completely resolved once the carcinoma was resected.


2007 ◽  
Vol 131 (10) ◽  
pp. 1555-1560
Author(s):  
Konstantin Shilo ◽  
Tatiana Dracheva ◽  
Haresh Mani ◽  
Junya Fukuoka ◽  
Isabell A. Sesterhenn ◽  
...  

Abstract Context.—α-Methylacyl CoA racemase (AMACR) is an oxidative enzyme involved in isomeric transformation of fatty acids entering the beta-oxidation pathway. AMACR serves as a useful marker in establishing a diagnosis of prostatic malignancy; however, limited information is available in regard to its presence in pulmonary neoplasms. Objective.—To investigate AMACR expression within a spectrum of lung carcinomas and its correlation with patients' survival. Design.—Four hundred seventy-seven pulmonary carcinomas, including 150 squamous cell carcinomas, 150 adenocarcinomas, 46 typical carcinoids, 31 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 72 small cell carcinomas, were studied immunohistochemically using tissue microarray–based samples. Results.—Overall, pulmonary tumors were positive for AMACR in a significant percentage (47%) of cases. Among tumor types, 22% of squamous cell carcinoma, 56% of adenocarcinoma, 72% of typical carcinoid, 52% of atypical carcinoid, 70% of large cell neuroendocrine carcinoma, and 51% of small cell lung carcinoma were positive for AMACR. Furthermore, the Kaplan-Meier analysis revealed that the patients with AMACR-positive small cell carcinoma had better survival (19% vs 5% after 5 years, P = .04) than patients with AMACR-negative tumors. Such survival advantage was seen for patients with stage I–II (P = .01) but not stage III–IV small cell carcinomas (P = .58). Conclusions.—These results indicate that, similar to prostate cancer, the overexpression of AMACR frequently occurs in pulmonary carcinomas. Additionally, its positive correlation with outcome of stage I–II small cell lung carcinoma warrants further investigation of the AMACR role in the prognosis of this tumor.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1208
Author(s):  
Katarzyna Wadowska ◽  
Piotr Błasiak ◽  
Adam Rzechonek ◽  
Iwona Bil-Lula ◽  
Mariola Śliwińska-Mossoń

Background: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. Methods: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients’ sera and plasmas, along with IL-6, TNF-α, SAA1, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. Results: Glucose concentrations showed statistically significant (p < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. Conclusion: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB.


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