Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients

BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1 a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10 HSP60 and Mcl-1 is involved in the development of many tumors. OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and anti-Mcl-1 antibodies respectively by immunohistochemistry. RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I ∼ II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients. CONCLUSIONS: High expression of HSP10 HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients.

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The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures

Frontiers in Oncology ◽

10.3389/fonc.2021.567978 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tao Shi ◽

Shuai Zhu ◽

Hengjuan Guo ◽

Xiongfei Li ◽

Shikang Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Meta Analysis ◽

Small Cell ◽

Cochrane Library ◽

Small Cell Lung ◽

Resected Nsclc ◽

Nsclc Patients

IntroductionPrevious studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.ResultsA total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18–2.05, p < 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29–2.18, p < 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: OR = 1.27, 95% CI:1.01–1.59, p = 0.038), histology (ADC vs. SCC: OR = 0.54, 95% CI:0.38–0.77, p = 0.001), TNM stage (I vs. II–III: OR = 0.45, 95% CI:0.34–0.60, p = 0.000), smoking status (Yes vs No: OR = 1.43, 95% CI:1.14–1.80, p = 0.002) and lymph node metastasis (N+ vs N−: OR = 1.97, 95% CI:1.26–3.08, p = 0.003).ConclusionsThe results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.

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A nomogram for predicting overall survival in resected non-small cell lung cancer with chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21064 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21064-e21064

Author(s):

Yuan Zeng ◽

Wenhua Liang ◽

Jianxing He

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Seer Database ◽

Small Cell Lung ◽

Lymph Node Count ◽

Resected Nsclc ◽

Nsclc Patients

e21064 Background: Chemotherapy is very common for resected Non-Small-Cell Lung Cancer (NSCLC) patients. However, models for predicting the survival outcomes of resected NSCLC patients with chemotherapy are scarce. The aim of this study was to develop a clinical nomogram for predicting overall survival in these patients. Methods: A total of 16661 resected NSCLC with chemotherapy were cases extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the prognostic factors to build a nomogram.The model was subjected to bootstrap internal validation with the SEER database and external validations with 1108 patients from China. The predictive accuracy and discriminative ability were illustrated by calibration, concordance index (C-index) and risk group stratification. Results: On multivariate analysis independent factors for OS were age, sex, examined lymph node count, extent of surgery, N stage, T stage and grade which were then integrated into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year OS showed excellent agreement between nomogram prediction and actual observation. The C-index of the nomogram was higher than that of AJCC 8th edition system for predicting OS (training cohort, 0.61 vs. 0.58; P < 0.01; validation cohort, 0.66 vs. 0.63, P = 0.56). The stratification into different risk groups allowed significant distinction between survival curves. Conclusions: We established a nomogram that can provide individual prediction of OS for resected NSCLC patients with chemotherapy. This practical prognostic model may help clinicians for treatment planning and to guide future studies.

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Low TIP30 Protein Expression is Associated with a High Risk of Metastasis and Poor Prognosis for Non-Small-Cell Lung Cancer

Journal of Clinical Medicine ◽

10.3390/jcm8010083 ◽

2019 ◽

Vol 8 (1) ◽

pp. 83 ◽

Cited By ~ 1

Author(s):

Chao-Ju Chen ◽

Po-An Chou ◽

Ming-Shyan Huang ◽

Yu-Peng Liu

Keyword(s):

Lung Cancer ◽

Protein Expression ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients

Non-small-cell lung cancer (NSCLC) is a deadly malignancy with a high prevalence worldwide. A reliable biomarker that can predict the prognosis is required to determine the therapeutic strategy. TIP30 was first identified as a tumor suppressor. A number of mechanistic studies indicated that the downregulation of TIP30 enhances the stemness, migration and survival of NSCLC cells. However, the clinical relevance of TIP30 for the prognosis of NSCLC is unknown. From a meta-analysis of public microarray datasets, we showed the upregulation of TIP30 mRNA expression was associated with worse overall survival of NSCLC patients, which contradicted the tumor suppressive role of TIP30. It is worth noting that the TIP30 mRNA expression was not correlated with its protein expression in 15 NSCLC cell lines. The results from the immunohistochemistry of a tissue microarray showed the downregulation of the TIP30 protein expression was associated with a higher risk of metastasis. In addition, the decrease in TIP30 protein was correlated with worse overall and progression-free survival of the NSCLC patients. Multivariate analysis suggested the loss of TIP30 protein was an independent factor to predict the poor prognosis of NSCLC. Our data indicated that TIP30 protein, not mRNA, would be a potential prognostic biomarker of NSCLC.

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Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

Vaccines ◽

10.3390/vaccines9070689 ◽

2021 ◽

Vol 9 (7) ◽

pp. 689

Author(s):

Li-Chung Chiu ◽

Shu-Min Lin ◽

Yu-Lun Lo ◽

Scott Chih-Hsi Kuo ◽

Cheng-Ta Yang ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Disease Recurrence ◽

Small Cell ◽

Small Cell Lung ◽

Resected Nsclc ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.

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Abstract 5257: FGF9 overexpression promotes tumorigenic potential of non-small cell lung cancer (NSCLC) cells, and is associated with poor prognosis in NSCLC patients.

10.1158/1538-7445.am2013-5257 ◽

2013 ◽

Author(s):

Kota Ishioka ◽

Kenzo Soejima ◽

Hiroyuki Yasuda ◽

Keiko Ohgino ◽

Satoshi Yoda ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Small Cell Lung ◽

Tumorigenic Potential ◽

Nsclc Patients

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The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.684807 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiang Guo ◽

Dan Li ◽

Xiangyu Luo ◽

Ye Yuan ◽

Tian Li ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Endothelial Cell Proliferation ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Cerna Network ◽

Nsclc Patients

BackgroundThe occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.MethodsThe expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.ResultsExpression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.ConclusionsLINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.

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The impact of programmed death-ligand 1 expression on the prognosis of early-stage resected non-small cell lung cancer: A meta-analysis of literatures.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21004 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21004-e21004

Author(s):

Shuai Zhu ◽

Xiongfei Li ◽

Shikang Zhao ◽

Yanye Wang ◽

Xi Lei ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Meta Analysis ◽

Small Cell ◽

Cochrane Library ◽

Small Cell Lung ◽

Resected Nsclc ◽

Nsclc Patients

e21004 Background: Previous studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as a poor prognostic biomarker for the survival in advanced-stage non-small-cell lung cancer (NSCLC) patients. However, the value of PD-L1 expression for the prognosis of early-stage NSCLC patients after complete resection remains controversial. Here, we conduct a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in resected NSCLC. Methods: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched up until June 30 2019, for studies evaluating the expression of PD-L1 and prognosis of the resected NSCLC. Hazard ratios (HRs) with 95% confidence interval (CI) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also performed. Results: A total of 15 studies involving 3501 patients were enrolled. The pooled hazard ratio (HR) showed that PD-L1 expression was related to a much shorter DFS (HR = 1.63, 95% CI: 1.26-2.12, P = 0.022), as well a significantly worse OS (HR = 1.68, 95% CI: 1.32-2.14, P = 0.000). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: HR = 1.25, 95% CI:1.02-1.52, p = 0.028), tumor stage (III/IV vs. I/ II: HR = 2.39, 95% CI:1.85-3.08, p = 0.000), lymph node metastasis (N+ vs N-: HR = 3.54, 95%CI:2.56-4.88, p = 0.000) and smoking status (Yes vs No: HR = 1.37,95% CI:1.20-1.560, p = 0.000). Conclusions: The results of this meta-analysis suggest that PD-L1 expression predict an unfavorable prognosis in early-stage resected NSCLC. The role of individualized anti-PD-L1/PD-1immunotherapy in the adjuvant settings of resected NSCLC is worthy of being further investigated.

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Elevated expression of mcl-1 inhibits apoptosis and predicts poor prognosis in patients with surgically resected non-small cell lung cancer

Diagnostic Pathology ◽

10.1186/s13000-019-0884-3 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Qiuyuan Wen ◽

Yuting Zhan ◽

Hongmei Zheng ◽

Hongjing Zang ◽

Jiadi Luo ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Proliferation Index ◽

Small Cell Lung ◽

Elevated Expression ◽

Nsclc Patients

Abstract Background Mcl-1, an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-PARP) can serve as a marker of cell apoptosis. Previously we reported that treatment of Mnk inhibitor CGP57380 resulted in decreased Mcl-1 expression while increased c-PARP expression in non-small cell lung cancer (NSCLC) cells. In this study, we aimed to investigate association between Mcl-1 expression and clinicopathological features of NSCLC, and their correlation between Mcl-1 and both proliferation index (PI) and apoptotic index (AI) in NSCLC patients. Methods Tissue microarrays (TMA) including 350 cases of surgically resected NSCLC were utilize and stained with Mcl-1, Ki-67 and c-PARP antibodies, PI and AI were then evaluated, respectively. Results Higher Mcl-1 expression and PI were observed in NSCLC compared with non-cancerous lung tissues (non-CLT), while AI was significantly lower in lung adenocarcinoma (ADC) compared with non-CLT. Additionally, Mcl-1 expression in lung ADC was evidently higher than that of in lung squamous cell carcinoma (SCC). The elevated Mcl-1 expression was associated with PI, and inversely related to AI in NSCLC. NSCLC patients with elevated Mcl-1 expression and high PI, or with high Mcl-1 expression and low AI had remarkably shorter overall survival time than these patients with low Mcl-1 expression. Conclusions Elevated expression of Mcl-1 might be inversely proportional to disease progression of NSCLC patients by promoting cell proliferation and inhibiting apoptosis, and Mcl-1 might serve as novel biomarker of poor prognosis for NSCLC patients.

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Upregulation of Serum miR-629 Predicts Poor Prognosis for Non-Small-Cell Lung Cancer

Disease Markers ◽

10.1155/2021/8819934 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Fayong Liu ◽

Tianshui Li ◽

Ping Hu ◽

Li Dai

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

High Serum ◽

Small Cell ◽

Clinicopathological Parameters ◽

Healthy Controls ◽

Small Cell Lung ◽

Aberrant Expression ◽

Nsclc Patients

Non-small-cell lung cancer (NSCLC) is one of the most common types of cancer worldwide. Accumulating evidence has suggested that aberrant expression of microRNAs (miRNAs) is involved in the carcinogenesis and progression of NSCLC. The current study is aimed at investigating the clinical significance of serum miR-629 in NSCLC. The expression levels of serum miR-629 in patients with NSCLC, patients with nonmalignant lung diseases, and healthy controls were assessed by real-time quantitative polymerase chain reaction. Our results showed that serum miR-629 levels were significantly upregulated in NSCLC patients compared to the controls. Serum miR-629 exhibited better performance for discriminating NSCLC patients from healthy controls, compared to the traditional biomarkers CYFRA 21-1 and CEA. In addition, a high serum miR-629 level was positively correlated with adverse clinicopathological parameters including lymph node metastasis, differentiation, and clinical stage. Serum miR-629 was dramatically reduced in the NSCLC cases receiving surgical treatment. Moreover, the patients in the high serum miR-629 group suffered poorer overall survival and disease-free survival than those in the low serum miR-629 group. In conclusion, serum miR-629 might serve as a potential prognostic biomarker for NSCLC.

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