Gene Expression In Cancer Tissues Research Articles

Evaluation of the expression of miRNA-214 and circ-0005407 markers and their associated ZFAND3 gene in Oral squamous cell carcinoma

Background and objectiveCancer biomarkers serve as measurable indicators for the early detection of cancer, as they can be detected in sample tissues. They play a crucial role in optimizing decision-making in clinical practice. To advanve in this field, it is necessary to identify of markers with higher sensitivity, specificity, and positive predictive value. Therfore, wer have chosen to investigate the expression of multiple biomarkers simultaneously in oral squamous cell carcinoma. Materials and methodsIn this experimental study, we investigated the expression levels of miRNA-214, circ-0005407, and ZFAND3 genes using the quantitative RealTime PCR method. The samples examined included 30 samples of fresh cancerous tissue and adjacent normal tissue obtained from the Cancer Institute of Imam Khomeini Hospital. The data were analyzed using the dependent samples t-test and ANOVA test. FindingsThe mean CT values of circ-0005407, miRNA-214, and ZFAND3 in the cancerous and normal groups were (15.48 ± 1.62 & 13.23 ± 1.63), (16.64 ± 1.51 & 13.21 ± 1.29), and (14.41 ± 1.07 & 16.72 ± 1.28), respectively. There was a statistically significant difference in the expression levels of all markers in the two investigated groups (P˂0.05). The fold change levels in circ-0005407, miRNA-214, and ZFAND3 gene markers were (0.51,0.22,6.34) respectively, indicating an increase in gene expression in cancerous tissue compared to normal. However, the other two markers showed decreased expression in cancerous tissue compared to normal tissue. ConclusionBased on the data obtained regarding the change in expression levels of these markers in cancerous tissue compared to normal tissue, it seems that these biomarkers can be used in the early diagnosis of oral cancer.

The novel biomarker LUNAR1 overexpression in cervical cancerous tissues specimens and its association with clinicopathological properties

BackgroundCervical cancer (CC) constitutes the fourth prevalent malignancy and cause of mortality in women worldwide. LUNAR1 is a specific LncRNA that promotes cancer cells through Notch signaling. However, molecular mechanisms of LUNAR1 in the CC progression remain obscure. In the present research, the LUNAR1 gene expression in CC tissue compared with adjacent non-cancerous tissue specimens and its association with the changing of LUNAR1 expression and clinicopathological properties of CC patients were perused. MethodsAfter collecting 115 pairs of CC tissue specimens and adjacent non-cancerous tissue, the processes of total RNA extraction and cDNA synthesis were performed. The differences in LUNAR1 expression in cancerous tissue and adjacent non-cancerous samples were detected through the qRT-PCR. Eventually, the differences of LUNAR1 expression and its linked with patients' clinicopathological properties and the potential of LUNAR1 to serve as a biomarker were evaluated. ResultsSignificant overexpression of the LUNAR1 occurred in CC tissue compared with adjacent non-cancerous tissue specimens (P < 0.001). Our results illustrated a meaningful association between the LUNAR1 overexpression, lymph node metastasis (P = 0.047), and cervical tumor invasion depth (P = 0.002). The ROC curve representative the potential biomarker's function of LUNAR1 with AUC, sensitivity%, and specificity%, 0.95, 77 %, and 99 %, respectively (P < 0.0001; 95 % CI = 0.92–0.97). ConclusionsProbably, the LUNAR1 could be involved as a novel oncogenic LncRNA in the progression of CC due to the substantial overexpression in cervical cancerous tissue specimens. The high sensitivity% and specificity% of LUNAR1 suggested that LUNAR1 could be a potential therapeutic and diagnostic biomarker for CC patients.

Upregulated Ly-6 gene expression is associated with poor overall survival in uterine corpus endometrial carcinoma patients

Abstract The human Ly-6 (hLy-6) gene family has recently gained interest for its possible role in tumor progression. High expression of hLy-6 genes is associated with poor overall survival in pancreatic ductal adenocarcinoma patients. To expand upon this work, we have carried out in silico analyses of all known hLy-6 gene expression in other cancers using TNMplot which shows differential gene expression in cancer tissues. We have also analyzed the patient survival by Kaplan-Meier plotter after mining the TCGA database. We report that upregulated expression of several hLy-6 genes is associated with poor cancer patient survival in many other cancer types, especially uterine corpus endometrial carcinoma (UCEC). Importantly, the expression of a number of hLy-6 genes is elevated in UCEC tissue when compared to the expression in normal uterine tissue. Further analysis of tumor-specific expression of the hLy-6 gene family is needed to uncover the function of Ly-6 proteins as well as the signaling pathways these proteins trigger that endow tumor survival and poor patient prognosis. Human Ly-6 gene products can potentially be used as biomarkers for cancer detection and as tumor associated antigens to identify high-risk cancer patients and appropriately design and/or calibrate cancer treatments for such patients.

Evaluation of the association between centrosome amplification in tumor tissue of breast cancer patients and changes in the expression of CETN1 and CNTROB genes

One of the contributing factors of cancer is the chromosomal aberration caused by centrosome amplification (CA). Changes in the expression of centrosomal genes can cause centrosomal abnormalities. Among the genes involved are CETN1 and CNTROB. Considering the importance and prevalence of breast cancer the aim of this study was to investigate the expression of these genes and its association with CA in breast cancer in women. In this case-control study, 40 breast cancer patients were referred to Mehr hospital selected and invasive breast cancer was confirmed by pathological tests. IHC method was done on paraffin-embedded breast cancer tissue to evaluate centrosome amplification by targeting Pericentrin antibody. Real-time PCR performed to gene expression of CETN1 and CNTROB. The data were analyzed by t-test and ANOVA test. The results showed that CA in breast tumor cells significantly was more than adjacent normal cells (p ≤ 0.05). Results of CETN1 and CNTROB gene expression showed increase expression in tumor tissue compared to control, respectively (p = 0.01, P = 0.02). Our finding showed that alterations of CETN1 and CNTROB gene expression in cancer tissues of patients were excessive in comparison with normal tissues, which could cause cell proliferation, tumor growth and metastasis. It is suggested to find basic strategies for diagnosis and treatment of breast cancer needed more samples of breast cancer, and other genes involved in the function of centrosomes.

The Effect of Endurance Training Along with Curcumin on VEGF-A Level and VEGFR Gene Expression in Cancer Tissue of Female Mice with Breast Cancer

The Effect of Endurance Training Along with Curcumin on VEGF-A Level and VEGFR Gene Expression in Cancer Tissue of Female Mice with Breast Cancer

Clinical Significance of PRKCI Gene Expression in Cancerous Tissue in Patients With Gastric Cancer.

The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.

The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population.

The molecular mechanism of hepatocellular carcinoma (HCC) is related to DNA damage caused by oxidative stress products induced by hepatitis B virus (HBV) or C (HCV) infection and exposure to environmental pollutants. Single-nucleotide polymorphisms (SNPs) of DNA damage response (DDR) genes may influence individual susceptibility to environmental risk factors and affect DNA repair efficacy, which, in turn, can influence the risk of HCC. The study evaluates a panel of 15 SNPs in 11 DDR genes (XRCC1, XRCC3, XPD, MUTYH, LIG1, LIG3, hOGG1, PARP1, NFIL1, FEN1, and APEX1) in 65 HCC patients, 50 HBV- and 50 HCV-infected non-cancerous patients, and 50 healthy controls. It also estimates the mRNA expression of nine DDR genes in cancerous and adjacent healthy liver tissues. Two of the investigated polymorphisms (rs1052133 and rs13181) were associated with HCC risk. For all investigated genes, the level of mRNA was significantly lower in HCC cancer tissue than in non-cancerous liver tissue. Seven of the investigated polymorphisms were statistically related to gene expression in cancer tissues. The disruption of DDR genes may be responsible for hepatocellular transformation in HCV-infected patients.

Abstract 1518: Lung adenocarcinoma differential expression analysis using the Maverix RNA-Seq pipeline

Abstract Background RNA-Seq is a powerful means of identifying changes in gene expression in cancerous tissue. Widespread adoption of RNA-Seq is hampered by lack of familiarity with the appropriate analysis tools and excessive turn around time. Maverix Biomics, Inc offers a scalable, reliable, validated, and easily accessible differential expression pipeline for translational and clinical researchers to analyze and explore RNA-Seq data. Here we describe the pipeline, demonstrate the available tools and visualizations, and provide benchmarks for completion time from lung adenocarcinoma. Results Lung adenocarcinoma samples appear very different compared to their normal counterparts in terms of overall gene expression and exhibit many differentially expressed genes. For analysis completion time, parallelization is far superior than the theoretical curve without parallelization. It took 7.9 hours to analyze two samples, but took only 13.1 hours to analyze 25 samples. We found 2246 significant genes common to three different differential expression tools: DESeq, edgeR, and cuffdiff. Conclusions The Maverix RNA-Seq pipeline is demonstrated here to be highly scalable, easy to use, and includes a range of tools and visualizations for understanding differential expressions results. This pipeline is a great analytic option to accelerate translational and clinical research in the field of oncology. Citation Format: Michael S. Fitzsimons, Mei-Chong Wendy Lee, Byung-In Lee, Lenin Subramanian. Lung adenocarcinoma differential expression analysis using the Maverix RNA-Seq pipeline. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1518.

A seven-gene CpG-island methylation panel predicts breast cancer progression.

BackgroundDNA methylation regulates gene expression, through the inhibition/activation of gene transcription of methylated/unmethylated genes. Hence, DNA methylation profiling can capture pivotal features of gene expression in cancer tissues from patients at the time of diagnosis. In this work, we analyzed a breast cancer case series, to identify DNA methylation determinants of metastatic versus non-metastatic tumors.MethodsCpG-island methylation was evaluated on a 56-gene cancer-specific biomarker microarray in metastatic versus non-metastatic breast cancers in a multi-institutional case series of 123 breast cancer patients. Global statistical modeling and unsupervised hierarchical clustering were applied to identify a multi-gene binary classifier with high sensitivity and specificity. Network analysis was utilized to quantify the connectivity of the identified genes.ResultsSeven genes (BRCA1, DAPK1, MSH2, CDKN2A, PGR, PRKCDBP, RANKL) were found informative for prognosis of metastatic diffusion and were used to calculate classifier accuracy versus the entire data-set. Individual-gene performances showed sensitivities of 63–79 %, 53–84 % specificities, positive predictive values of 59–83 % and negative predictive values of 63–80 %. When modelled together, these seven genes reached a sensitivity of 93 %, 100 % specificity, a positive predictive value of 100 % and a negative predictive value of 93 %, with high statistical power. Unsupervised hierarchical clustering independently confirmed these findings, in close agreement with the accuracy measurements. Network analyses indicated tight interrelationship between the identified genes, suggesting this to be a functionally-coordinated module, linked to breast cancer progression.ConclusionsOur findings identify CpG-island methylation profiles with deep impact on clinical outcome, paving the way for use as novel prognostic assays in clinical settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1412-9) contains supplementary material, which is available to authorized users.

PWE-001 Field Cancerisation Theory In Colorectal Cancer (crc): What Role Do Fibroblast Growth Factors Have?

IntroductionCharacterisation of the molecular field defect around colorectal cancer (CRC) could enable identification of novel biomarkers that could be used for early detection of CRC. Previous studies have suggested fibroblast...

Increasing Cancer-Specific Gene Expression by Targeting Overexpressed α5β1 Integrin and Upregulated Transcriptional Activity of NF-κB

We developed a modular multifunctional nonviral gene delivery system by targeting the overexpressed cancer surface receptor α5β1 integrin and the upregulated transcriptional activity of the cancer resistance mediating transcription factor NF-κB, thereby introducing a new form of transcriptional targeting. NF-κB regulated therapy can improve specificity of gene expression in cancer tissue and also may offset NF-κB mediated cancer resistance. We delivered a luciferase gene under the control of an NF-κB responsive element (pNF-κB-Luc) encapsulated in a PR_b peptide functionalized stealth liposome that specifically targets the α5β1 integrin and achieved increased gene expression in DLD-1 colorectal cancer cells compared to BJ-fibroblast healthy cells in vitro. The multitargeted system was also able to differentiate between cancer cells and healthy cells better than either of the individually targeted systems. In addition, we constructed a novel cancer therapeutic plasmid by cloning a highly potent diphtheria toxin fragment A (DTA) expressing gene under the control of an NF-κB responsive element (pNF-κB-DTA). A dose-dependent reduction of cellular protein expression and increased cytotoxicity in cancer cells was seen when transfected with PR_b functionalized stealth liposomes encapsulating the condensed pNF-κB-DTA plasmid. Our therapeutic delivery system specifically eradicated close to 70% of a variety of cancer cells while minimally affecting healthy cells in vitro. Furthermore, the modular nature of the nonviral design allows targeting novel pairs of extracellular receptors and upregulated transcription factors for applications beyond cancer gene therapy.

Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue

Deregulated expression of clock gene per2 has previously been associated with progression of cancer. The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. Patients surgically treated for colorectal carcinoma with up-regulated and down-regulated per2 expression in cancer versus adjacent tissue were studied. Total RNA from cancer tissue of these patients was used to specify genes associated with altered per2 expression using the Human Cell Cycle RT(2) profiler PCR array system. We identified seven genes positively correlated (hus1, gadd45α, rb1, cdkn2a, cdk5rp1, mre11a, sumo1) and two genes negatively correlated (cdc20, birc5) with per2 expression. Expression of these seven genes was subsequently measured by real time PCR in all patients of the cohort. Patients were divided into three groups according to TNM classification. We observed an increase in gene expression in cancer tissue compared to adjacent tissue in the first group of patients in all genes measured. Expression of genes positively associated with per2 gene expression was dependent on tumor staging and changes were observed preferentially in cancer tissue. For genes negatively associated with per2 expression we also detected changes in expression dependent on tumor staging. Expression of cdc20 and birc5 was increasing in the proximal tissue and decreasing in the cancer tissue. These results implicate functional involvement of per2 in the process of carcinogenesis via newly uncovered genes. The relevancy of gene expression for determination of diagnosis and prognosis should be considered in relation to tumor staging.

Lipogenic gene expression profile in patients with gastric cancer

Numerous types of cancer exhibit increased lipogenesis and expression of lipogenic enzymes and transcription factors, including sterol regulatory element-binding protein-1. Lipogenic gene expression is upregulated at the mRNA level, in concert with metabolic pathways associated with changes in expression and/or activity of lipogenic transcription factors. However, this expression pattern in human gastric carcinoma has not been elucidated. In this study, lipogenic gene expression in cancer tissues was investigated using quantitative PCR. In patients with gastric cancer, carnitine O-palmitoyltransferase type I mRNA and miR-33b were significantly downregulated, suggesting that miR-33b downregulation is mediated by conditions that also affect the expression and/or activity of transcription factors involved in lipogenic gene expression. Consequently, the association between miR-33b and gastric cancer may provide a novel strategy for the genetic diagnosis of gastric cancer. However, additional studies including a larger number of samples are required to confirm these results.

AN ASSOCIATION RULE MINING APPROACH FOR CO-REGULATED SIGNATURE GENES IDENTIFICATION IN CANCER

When a normal cell becomes cancerous there will be change in expression of many genes in that cell. Identification of these changes in gene expression in cancer tissue may lead to the development of novel tools for early diagnosis and effective therapeutics. In this paper we present an association rule mining approach to identify the association between the genes that are differentially expressed in cancer tissue compared to normal tissue. We design an association rule mining algorithm GeneExpMiner for gene expression data mining. Serial Analysis of Gene Expression (SAGE) data related to pancreas cancer is used to demonstrate the approach. It is expected that the approach will help in developing better treatment methodologies for cancer and designing low cost microarray chips for diagnosing cancer. The results have been validated in terms of Gene Ontology and the signature genes that we have identified are matching with the published data.

Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer

Laser microdissection (LMD) and microarray were used to identify genes associated with colorectal cancer. Stanniocalcin 2 (STC2) expression and clinicopathological significance in 139 clinical colorectal cancer samples were specifically investigated using real-time quantitative reverse transcription-polymerase chain reaction. A number of genes upregulated in colorectal cancer cells compared to normal colorectal epithelial cells were identified including STC2. STC2 gene expression in cancer tissue was higher than in corresponding normal colorectal epithelial tissue in 124 of 139 cases (89.2%, p < 0.01). Tumors with high STC2 expression showed higher frequencies of lymph node metastasis, lymphatic invasion, tumor depth, tumor size and AJCC Stage classification (p < 0.01). Patients with high STC2 expression also showed significantly worse overall survival rates than those with low STC2 expression (p < 0.01). Furthermore, STC2 gene appeared to be associated with colorectal cancer progression and may be a useful prognostic indicator for colorectal cancer.

Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancer

Mitotic centromere-associated kinesin (MCAK) is a microtubule (MT) depolymerase necessary for ensuring proper kinetochore MT attachment during spindle formation. To determine MCAK expression status and its clinicopathological significance, real-time reverse transcriptase–polymerase chain reaction was used in 65 cases of gastric cancer. MCAK gene expression in cancer tissue was significantly higher than expression in non-malignant tissue (P<0.05). Elevated MCAK expression was significantly associated with lymphatic invasion (P=0.01) and lymph node metastasis (P=0.04). Furthermore, patients with high MCAK expression had a significantly poorer survival rate than those with low MCAK expression (P=0.008). Immunohistochemical study revealed that expression of MCAK was primarily observed in cancer cells. Additionally, a gastric cancer cell line (AZ521) that stably expressed MCAK was established and used to investigate the biological effects of the MCAK gene. In vitro results showed that cells transfected with MCAK had a high rate of proliferation (P<0.001) and increased migratory ability (P<0.001) compared to mock-transfected cells. This study demonstrated that elevated expression of MCAK may be associated with lymphatic invasion, lymph node metastasis, and poor prognosis. These characteristics may be due in part to the increased proliferative and migratory ability of cells expressing MCAK.

CEACAM6 gene expression in intrahepatic cholangiocarcinoma

The purpose of this study was to investigate the clinicopathological and biological significance of human carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) gene expression in human intrahepatic cholangiocarcinoma. CEACAM6 is reported to be involved in human malignancies. However, in cholangiocarcinoma expression of CEACAM6 and its clinicopathological significance have not been investigated. CEACAM6 expression status was determined and analysed with respect to various clinicopathological parameters in 23 intrahepatic cholangiocarcinomas. Additionally, we investigated effects of CEACAM6 gene in the cholangiocarcinoma cell lines. CEACAM6 gene expression in cancer tissues was higher than in noncancerous tissues in 16 of the 23 cases; however, it was not statistically significant. The tumours with elevated CEACAM6 expression showed a tendency to be associated with lymphatic invasion and stage of the disease. Interestingly, patients with high CEACAM6 expression showed a significantly poorer disease-free survival rate than those with low CEACAM6 expression. We demonstrated that CEACAM6-transfected cells were more proliferative, more invasive and more chemoresistant to gemcitabine compared to mock-transfected cells. Furthermore, CEACAM6 gene silencing by CEACAM6-specific siRNA resulted in higher chemosensitivity to gemcitabine. CEACAM6 is a potential prognostic indicator and potential chemoresistant marker to gemcitabine for patients with intrahepatic cholangiocarcinoma.

Clinicopathologic and Biological Significance of Kallikrein 6 Overexpression in Human Gastric Cancer

Human kallikrein genes (KLK) have been reported to be involved in human malignancies and several KLKs are promising biomarkers of prostate, ovarian, testicular, and breast cancers. Herein, we investigated the clinicopathologic and biological significance of KLK6 gene expression in human gastric cancer. Using real-time reverse transcription-PCR, we analyzed the KLK6 expression status with respect to various clinicopathologic variables in 66 patients with gastric cancer. In addition, we established a KLK6 stably suppressed gastric cancer cell line (MKN28) using small interfering RNA-mediated gene silencing, and investigated its effects on the cell proliferation rate, cell cycle, and invasiveness. The KLK6 gene expression in cancerous tissue (0.37 +/- 0.53) was significantly (P < 0.000001) higher than that in noncancerous tissue (0.026 +/- 0.060). Elevated KLK6 expression was significantly associated with lymphatic invasion (P = 0.03). Furthermore, patients with a high KLK6 expression had a significantly poorer survival rate than those with a low KLK6 expression (P = 0.03). Therefore, we showed that KLK6 gene silencing with KLK6 small interfering RNA effectively suppressed the cell proliferation rate (P = 0.002), cell population in the S phase (P < 0.01), and invasiveness (P < 0.01) in comparison to mock-transfected cells. The KLK6 gene is markedly overexpressed in gastric cancer tissue and its expression status may be a powerful prognostic indicator for patients with gastric cancer. Our findings also suggest that KLK6 may possibly be a novel target for gastric cancer therapy by gene-silencing procedures.

CDNA microarray analysis with amplified RNA after isolation of intact cellular RNA from neoplastic and non-neoplastic prostate tissue separated by laser microdissections

Laser microdissection is a valuable tool to prepare pure cell populations from complex tissues for further analyses. Gene expression studies by real-time RT-PCR and cDNA arrays of microdissected tissues are becoming widely used methods. The integrity and quantity of prepared RNA must be proven to ensure reliable results in subsequent applications such as quantitative RT-PCR and cDNA-arrays. In the present study we used RNAlater trade mark protected prostate tissue for laser microdissection of tumor and tumor-free tissues. RNA quality and quantity was assessed using automated capillary gel electrophoresis. By using quantitative real time-RT-PCR before and after mRNA amplification the insulin-like growth factor binding protein-3 (IGFBP-3) gene expression was shown to be down-regulated in three out of five cases and DD3 was up-regulated in cancer tissues in all cases. The up-regulation of DD3 and the down-regulation of IGFBP-3 gene expression in cancer tissue were conserved after RNA amplification. A cDNA microarray also revealed an IGFBP-3 down-regulation in cancer tissue as well as several genes known to be differerentially expressed in prostate cancer. Taken together, we present a novel method for the isolation of intact RNA from laser microdissection-derived prostate cancer tissue useful for downstream applications of real-time RT-PCR and cDNA microarrays.

Clinical significance of MDR1 and MDRP gene expression in patients with non-small cell lung cancer.

To investigate the clinical significance of MDR1 andMDRP gene expression in patients with non-small cell lung cancer (NSCLC) . Using reverse transcription polymerase chain reaction (RT-PCR) technique , the expression of MDR1 and MDRP gene was determined in cancer and paracancerous tissues from 33 NSCLC patients. Positive expression of MDR1 gene was 69.7% and 36.4% in lung cancer tissues and paracancerous tissues respectively , and a highly significant difference was observed between the two groups ( P < 0.01) . The expression levels of MDR1 mRNA were much higher than those in paracancerous tissues. The positivity rate of MDRP gene expression in cancer tissues was 63.6% , which was higher than 30.3% in paracancerous tissue. The gene expression levels in cancer tissues were also significantly higher than those in paracancerous tissues. The expression levels of MDR1 and MDRP in cancer tissues of the patients receiving pre-operative chemotherapy were remarkably higher than those of the patients not receiving chemotherapy ( P < 0.05) . NSCLC had primary and acquired multidrug resistance. It was of important significance to detect MDR1 and MDRP gene expression in directing chemotherapy of lung carcinoma and in predicting prognosis.