OBJECTIVE: Human U three protein 14a (hUTP14a) facilitates tumorigenesis through promoting p53 and Rb degradation as well as enhancing c-Myc oncogenic activity. Moreover, hUTP14a expression is up-regulated in human hepatocellular cancer and colorectal cancer tissues. In this study, the expression of hUTP14a in non-small cell lung cancer (NSCLC) tissues was evaluated by immunohistochemistry staining (IHC). The relationship between hUTP14a expression levels and the clinical characteristics of the NSCLC patients were analyzed. METHODS: Lung cancer tissues and the adjacent non-cancerous tissues were collected from 123 cases of NSCLC patients including 53 cases of squamous cell carcinoma (SCC) and 70 cases of adenocarcinoma (ADC), who had accepted surgical resection at Peking University Third Hospital from May 2003 to April 2006. The expression level of hUTP14a was determined by IHC in human NSCLC tissues and the adjacent non-cancerous tissues. The associations between hUTP14a expression and the clinical pathological variables including gender, age, tumor size, histological type, differentiation degree and clinical pathological stage were analyzed using the Pearson's χ² test. RESULTS: The expression rate of hUTP14a in NSCLC tissues was significantly higher than that in the non-cancerous tissues (37.4% vs. 0, P<0.001). The expressions of hUTP14a in lung ADC and SCC were 48.6% and 20.6%, respectively. The expression rate of hUTP14a in both lung ADC and SCC was significantly higher than that in the adjacent non-cancerous tissues (P<0.001). In addition, the expression rate of hUTP14a in lung ADC was significantly higher than that in SCC (χ²=8.66, P=0.003). Furthermore, the expression rate of hUTP14a in the late pTNM stage of SCC was significantly higher than that in the early pTNM stage of SCC while hUTP14a expression level was not associated with pTNM stage of ADC. No correlation was found between hUTP14a expression and the other clinical pathologic features of the patients. CONCLUSION Expression of hUTP14a was up-regulated in NSCLC tissues and was correlated with pTNM stage of SCC, suggesting that hUTP14a might possess a potential as a candidate marker for the early diagnosis screening of NSCLC.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Humans ; Lung Neoplasms ; Prognosis ; Ribonucleoproteins, Small Nucleolar/metabolism*

Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; genetics ; metabolism

Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as KRAS. Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.
Biology ; Carcinoma, Non-Small-Cell Lung ; Glutamine ; Glycolysis ; Humans ; Lung Neoplasms ; Metabolism ; Up-Regulation

Non-small cell lung cancer is one of the leading causes of all cancer deaths, but despite years of research, it is still difficult to predict the response and clinical outcome of the disease. In recent years, new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed. EGFR is one of the most frequently over expressed proteins in various cancers, including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, EGFR has become an attractive target for various treatment strategies. However, it is important to note that not all patients with lung cancer are suitable for targeted treatment, and that patients should be selected for this treatment. Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with, and predict the likelihood of response to EGFR targeted therapy. There are many standard techniques to be used for the detection of EGFR. This overview summarizes the ongoing and future investigations to determine the status of the EGFR.
Carcinoma, Non-Small-Cell Lung ; blood ; metabolism ; Humans ; Receptor, Epidermal Growth Factor ; blood ; metabolism

Chemokine-like factor-like MARVEL transmembrane domain containing member/chemokine-like factor superfamily member (CMTM/CKLFSF) including CKLF and CMTM1-CMTM8 are a new family of proteins linking chemokines and transmembrane superfamilies. CMTM not only have broad chemotactic activities, but also associate with hematopoietic system, immune system, and tumor development and metastasis closely. CMTM proteins are involved in key biological processes of cancer development, which include activation and recycling of growth factor receptors, cell proliferation and metastasis, and regulation of the tumor immune microenvironment. This is a new focus of research on the relationship between CMTM and tumors, because CMTM4/CMTM6 can be considered as a regulator for programmed cell death ligand 1 (PD-L1). This paper reviews the role of CMTM family members on cancer, especially in tumor growth, metastasis and immune escape, summarize the latest findings on the relationship between CMTM and non-small cell lung cancer, and explores the potential clinical value of CMTM as a novel drug target or biomarker.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms ; MARVEL Domain-Containing Proteins/metabolism* ; Cell Proliferation ; Chemokines/metabolism* ; Tumor Microenvironment

Carcinoma, Non-Small-Cell Lung ; diagnosis ; metabolism ; therapy ; Humans ; Lung Neoplasms ; diagnosis ; metabolism ; therapy ; Receptor Protein-Tyrosine Kinases ; metabolism

OBJECTIVETo analyze the relationship between DNA content and biological behavior and its prognostic significance in non-small cell lung cancer.

METHODSTumor DNA content was determined by flow cytometry in the specimens from 58 patients with resected non-small cell lung cancer. The DNA content of each cell subpopulation was expressed as the DNA index (DI), and an internal standard was provided by the normal pulmonary parenchymal cells in the same specimen. The prognostic value of DNA content in non-small cell lung cancer was assessed by Cox's model analysis.

RESULTSIn qualitative analysis, there was no relationship between DNA ploidy (diploidy or aneuploidy) and the following factors: tumor size, metastasis of lymph node, clinical stage, pathologic type, pathologic grade or survival. In quantitative analysis, high DNA index was observed in tumor size > 3 cm, metastasis of lymph node, stage III/IV, adenocarcinoma and shorter survival, which was statistically significant. Cox's model analysis showed that DNA index was a prognostic factor in non-small cell lung cancer and DNA index > 2.0 was an independent prognostic factor.

CONCLUSIONDNA index analysis is useful for the evaluation of the biological behavior and the prognosis of non-small cell lung cancer.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; DNA, Neoplasm ; metabolism ; Female ; Humans ; Lung Neoplasms ; metabolism ; Male ; Middle Aged

OBJECTIVETo investigate the clinical significance of phosphorylated caspase-8 by Src in patients with operable non-small cell lung cancer.

METHODSSrc and caspase-8 expressions were tested using immunohistochemistry in non-small cell lung cancer tissues and control lung tissues. The expression of phosphorylated caspase-8 at 380 tyrosine by Src was detected using Western blotting. The disease-free survival (DFS) of patients positive and negative for phosphorylated caspase-8 was analyzed with Kaplan-Meire survival curve.

RESULTSNo significant difference was found in the positivity rate of caspase-8 or Src between the cancer tissues and control lung tissues (76.3% vs 83.3%, P>0.05; 70.1% vs 66.4%, P>0.05). All the patients with Casp8- and Src-positive cancers were positive for phosphoryalted caspase-8, whose expression rate was significantly higher in the cancer tissues than in the paired control lung tissues (52.4% vs 7.1%, P<0.05). The 2-year DFS was significantly higher in patients negative for phosphorylated caspase-8 than in the positive patients (32.0% vs 60.3%, P<0.05).

CONCLUSIONPhosphorylated caspase-8 may serve as a predictor for a poorer DFS in patients with operable non-small cell lung cancer.

Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Caspase 8 ; metabolism ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; Phosphorylation

The incidence and mortality of lung cancer rank top in China. One important factor is the occurrence of metastasis. With the development of science technology, the effect of surgical treatment on lung cancer is improved. Moreover, the use of targeted therapy has achieved a new height for the treatment of lung cancer. However, the recurrence rate remains high even the tumor was completely resected at early stage. The occurrence of lymph node micrometastasis is considered as one of the plausible explanations. The difficulty indetecting micrometastasis has been greatly reduced. Although studies dig deeper into the lymph node micrometastasis, there are still some controversies including the selection of surgical procedures, the pathological staging and prognosis about patients with lymph node micrometastasis. This review manages to generalize the latest research progress of lymph node micrometastasis.
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Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Neoplasm Micrometastasis ; Risk Factors

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1 alpha (HIF-1 alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1 alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1 alpha positive carcinomas, MVD was significantly higher in HIF-1 alpha positive SCCs than in HIF-1 alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1 alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1 alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.
Adenocarcinoma/metabolism* ; Adenocarcinoma/pathology ; Animals ; Antigens, CD34/metabolism ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Carcinoma, Squamous Cell/metabolism* ; Carcinoma, Squamous Cell/pathology ; Cell Division/physiology* ; Human ; Immunohistochemistry ; Proliferating Cell Nuclear Antigen/metabolism ; Survival Rate ; Transcription Factors/metabolism* ; Vascular Endothelial Growth Factor A/metabolism