Path Planning and Navigation of Miniature Serpentine Robot for Bronchoscopy Application.

The miniature serpentine robot can be applied to NOTES (Natural Orifice Transluminal Endoscopic Surgery). In this paper, a bronchoscopy application is addressed. This paper describes the basic mechanical design and control scheme of this miniature serpentine robotic bronchoscopy. In addition, off-line backward path planning and real-time and in situ forward navigation in this miniature serpentine robot are discussed. The proposed backward-path-planning algorithm utilizes the 3D model of a bronchial tree constructed from the synthetization of medical images such as images from CT (Computed Tomography), MRI (Magnetic Resonance Imaging), or X-ray, to define a series of nodes/events backward from the destination, for example, the lesion, to the original starting point, for example, the oral cavity. Accordingly, forward navigation is designed to make sure this series of nodes/events shall be passed/occur from the origin to the destination. This combination of backward-path planning and forward navigation does not require accurate positioning information of the tip of the miniature serpentine robot, which is where the CMOS bronchoscope is located. Collaboratively, a virtual force is introduced to maintain the tip of the miniature serpentine robot at the center of the bronchi. Results show that this method of path planning and navigation of the miniature serpentine robot for bronchoscopy applications works.

The Long Noncoding RNA LINC00665 Facilitates c-Myc Transcriptional Activity via the miR-195-5p MYCBP Axis to Promote Progression of Lung Adenocarcinoma.

Long noncoding RNAs (lncRNAs) have recently received growing substantial attention in cancer research due to their important roles in various cancer types. However, the underlying mechanisms and functions of lncRNAs, especially in lung adenocarcinoma (LUAD), remain elusive. Based on pan-cancer screening analyses, we identified that the noncoding RNA LINC00665 was up-regulated in lung adenocarcinoma, which was subsequently confirmed in clinical samples and cell lines. Higher expression of LINC00665 was positively associated with poor prognosis and advanced T stage. Next, using gain- and loss- of function approaches, we revealed that LINC00665 promotes cell proliferation, cell migration, invasion, and suppresses cell apoptosis in LUAD through in vitro and in vivo experiments. Additionally, our findings showed that LINC00665 was predominately localized in the cytoplasm so as to interact with Ago2 protein, which could function as miRNA sponges. The results of bioinformatics prediction and RNA pull-down assay indicated that LINC00665 directly interacted with miR-195-5p. This was also confirmed by fluorescence colocalization. Furthermore, luciferase reporter assay demonstrated that Myc binding protein (MYCBP, also called AMY-1), which enhanced c-Myc transcriptional activity, was the target gene of LINC00665 dependent on miR-195-5p. Finally, rescue functional assay results uncovered that the oncogenic capability of LINC00665 was dependent on miR-195-5p and c-Myc transcriptional activity. In summary, this work elucidates that LINC00665 accelerates LUAD progression via the miR-195-5p/MYCBP axis by acting as a competing endogenous RNA (ceRNA), suggesting that LINC00665 may represent a potential therapeutic target for clinical intervention of LUAD.

KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway.

Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.

Integrative analysis of differential genes and identification of a "2-gene score" associated with survival in esophageal squamous cell carcinoma.

BACKGROUND: Developments in high-throughput genomic technologies have led to improved understanding of the molecular underpinnings of esophageal squamous cell carcinoma (ESCC). However, there is currently no model that combines the clinical features and gene expression signatures to predict outcomes. METHODS: We obtained data from the GSE53625 database of Chinese ESCC patients who had undergone surgical treatment. The R packages, Limma and WGCNA, were used to identify and construct a co-expression network of differentially expressed genes, respectively. The Cox regression model was used, and a nomogram prediction model was constructed. RESULTS: A total of 3654 differentially expressed genes were identified. Bioinformatics enrichment analysis was conducted. Multivariate analysis of the clinical cohort revealed that age and adjuvant therapy were independent factors for survival, and these were entered into the clinical nomogram. After integrating the gene expression profiles, we identified a "2-gene score" associated with overall survival. The combinational model is composed of clinical data and gene expression profiles. The C-index of the combined nomogram for predicting survival was statistically higher than the clinical nomogram. The calibration curve revealed that the combined nomogram and actual observation showed better prediction accuracy than the clinical nomogram alone. CONCLUSIONS: The integration of gene expression signatures and clinical variables produced a predictive model for ESCC that performed better than those based exclusively on clinical variables. This approach may provide a novel prediction model for ESCC patients after surgery.

KIF18B promotes tumor progression through activating the Wnt/ß-catenin pathway in cervical cancer.

BACKGROUND: KIF18B was identified as a potential oncogene by analysis of The Cancer Genome Atlas database. MATERIALS AND METHODS: We assessed KIF18B expression and explored its clinical significance in cervical cancer tissues. We have also evaluated the effects of KIF18B on cervical cancer cell proliferation, migration, and invasion both in vitro and in vivo. RESULTS: Our results show that KIF18B is overexpressed in cervical cancer tissues and is associated with a large primary tumor size, an advanced FIGO stage, and an advanced tumor grade. Knockdown of KIF18B induces cell cycle G1-phase arrest and inhibits the proliferation, migration, and invasion of cervical cancer cells, whereas its overexpression promotes proliferation, migration, and invasion in these cells. Moreover, silencing of KIF18B reduces expression of CyclinD1, ß-catenin, C-myc, and p-GSK3ß expression. CONCLUSION: These data suggest that KIF18B can serve as a novel oncogene that promotes the tumorigenicity of cervical cancer cells by activating Wnt/ß-catenin signaling pathway.

A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

OBJECTIVE: Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. METHODS: A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. RESULTS: A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. CONCLUSIONS: This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making.

Young age increases risk for lymph node positivity but decreases risk for non-small cell lung cancer death.

Non-small cell lung cancer (NSCLC) prognosis and risk of lymph node positivity (LN+) are reference points for reasonable treatments. The aim of the current study was to investigate the effect of age on LN+ and NSCLC death. Data from the Surveillance, Epidemiology, and End Results (SEER) registry were used to identify 82,253 patients with NSCLC diagnosed between 1988 and 2008. All the patients underwent standard lung cancer surgery with lymph node examination. Demographic and clinicopathological parameters were extracted and compared among each age group. Impact of age on LN+ and NSCLC death was evaluated by the Cochran-Armitage trend test and logistic univariate and multivariate analyses for all T stages. Overall, 22,711 (27.60%) patients of the entirety had lymph node metastasis and 28,968 (35.22%) patients died of NSCLC within 5 years. With the increase in age, LN+ rates decreased regardless of T stages (P<0.001), whereas NSCLC-specific mortality increased in stages T1-T3 (P<0.001). Controlling other covariates in multivariable logistic regression, age remained an independent risk factor for LN+ in all T stages (P<0.05) and in stages T1-T3 (P<0.05). Our SEER analysis demonstrated a higher rate of LN+ and lower mortality in younger patients with NSCLC, after accounting for other covariates.

Improvement of survival for non-small cell lung cancer over time.

Non-small cell lung cancer (NSCLC) is the main histological subtype of lung cancer, which is the leading cause of cancer death. It is unclear whether the improved survival seen at high-volume centers applies to the general population and, more importantly, whether the improvement in lung cancer survival was just a consequence of improved screening work. Data from the Surveillance, Epidemiology, and End Results (SEER) registry was used to identify 405,580 patients with NSCLC diagnosed from 1988 to 2008. The patients were divided into four groups according to the year of diagnosis. Trends of clinical characteristics were analyzed to reflect the progress of screening work. Five-year relative survivals in various subgroups were compared. The results indicated that proportion of aged, advanced, and non-surgical patients increased, whereas patients with lymph node metastasis and high histology grade decreased. Improvements in all stages of NSCLC patients were demonstrated, with relatively more significant gains for patients with localized and regional disease. After potentially curative surgical resection, remarkable improvements were observed in both cohorts with time (surgical: 52.00%-63.00%; non-surgical: 6.10%-13.50%). Specifically, patients who underwent pneumonectomy, lobectomy/bilobectomy, and partial/wedge/segmental resection all presented better survival rates. Our SEER analysis demonstrated improvements among patients in all stages of NSCLC that were deemed attributable to improved therapy and medical care for NSCLC rather than improved screening work.

Expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins in non-small cell lung cancer.

Insulin-like growth factor 2 messenger RNA-binding proteins have been described to associate with malignant process in many cancers. However, the role of insulin-like growth factor 2 messenger RNA-binding protein family has not been thoroughly elucidated in non-small cell lung cancer. This study was to investigate the expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins family in non-small cell lung cancer. The expression levels of IGF2BP1-IGF2BP3 in tumor and adjacent normal tissues were determined, and association with clinicopathological features and overall survival was investigated by analyzing The Cancer Genome Atlas lung cancer database. Proliferation, migration, invasion assays, and flow-cytometry analysis were used to investigate the biological function in vitro. Insulin-like growth factor 2 messenger RNA-binding protein expression levels were significantly increased in non-small cell lung cancer compared to adjacent normal lung tissues. Chi-square test indicated that IGF2BP1 and IGF2BP3 expressions correlated with some meaningful clinical characteristics in non-small cell lung cancer. Kaplan-Meier analysis showed that high-level expression of IGF2BP1 or IGF2BP3 predicted poor overall survival in lung adenocarcinoma patients. Multivariate regression analysis showed that high level of IGF2BP3 was an independent risk factor for poor prognosis in lung adenocarcinoma patients (hazard ratio = 1.616, p = 0.017). In vitro, knockdown of IGF2BP3 inhibited lung adenocarcinoma cell proliferation by inducing cell cycle arrest and apoptosis, and undermined abilities of migration and invasion, and overexpression of IGF2BP3 could promote malignant phenotypes in lung adenocarcinoma cells. Our study revealed that expression of insulin-like growth factor 2 messenger RNA-binding proteins was widely upregulated and correlated with some certain clinicopathological features in non-small cell lung cancer. Especially, in insulin-like growth factor 2 messenger RNA-binding protein family, IGF2BP3 might play the most important role in tumor aggressiveness and prognosis in lung adenocarcinoma, and IGF2BP3 might serve as a potential therapeutic target and a novel prognostic biomarker in lung adenocarcinoma patients.

CDCA2 promotes lung adenocarcinoma cell proliferation and predicts poor survival in lung adenocarcinoma patients.

Cell division cycle associated 2(CDCA2) is overexpressed in neuroblastoma and oral squamous cell carcinoma, and its overexpression positively correlates to tumor progression. However, the biological and clinical significance of CDCA2 in lung adenocarcinoma(LAC) has never been investigated. We determined the expression profile and clinical significance of CDCA2 using The Cancer Genome Atlas(TCGA) and tissue microarray(TMA). Furthermore, we explored the biological function of CDCA2 both in vitro and in vivo. A great upregulation of CDCA2 was observed in LAC tissues compared with adjacent normal tissues. Importantly, Cox regression analysis indicated that high level of CDCA2 was an independent risk factor for overall survival(OS) in LAC patients (TCGA: HR = 1.720, p = 0.004; TMA: HR = 1.971, p = 0.023). Inhibition of CDCA2 suppressed the proliferation of LAC cells via G1 phase arrest by downregulating cyclin E1(CCNE1), while overexpression of CDCA2 promoted LAC cells proliferation by upregulating CCNE1. Moreover, the oncogenic activity of CDCA2 was also confirmed in vivo. In conclusion, CDCA2 promotes proliferation of LAC cells and predicts poor prognosis in LAC patients. CDCA2 might play a significant role in LAC progression.

Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma.

The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p < 0.0001), and tumor size (p = 0.0116) in non-small-cell lung cancer patients. In lung adenocarcinoma patients, overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p < 0.0001), higher DNA ploidy level (p < 0.0001), and poor prognosis (hazard ratio = 2.39, confidence interval: 1.87-3.05, p < 0.0001). However, in lung squamous cell carcinoma patients, no significant association of cell division cycle 20 expression was observed with any clinical parameter or prognosis. Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

Upregulation of FAM83D promotes malignant phenotypes of lung adenocarcinoma by regulating cell cycle.

The family with sequence similarity 83, member D (FAM83D) gene is upregulated in hepatocellular carcinoma and ovarian cancer, and its overexpression has been reported to positively correlate with tumor progression. However, the clinical significance and biological function of FAM83D in lung adenocarcinoma has not been investigated. We determined the expression profile and clinical significance of FAM83D using The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) analysis. Considerable upregulation of FAM83D was observed in LUAD tissues compared with adjacent normal tissues, and its overexpression was significantly associated with more advanced clinicopathological characteristics. Importantly, multivariate Cox regression analysis indicated that a high level of FAM83D expression was an independent risk factor for worse overall survival in LUAD patients (HR = 1.692, P = 0.006). Inhibition of FAM83D suppressed the proliferation of LUAD cells via G1 phase arrest by downregulating cyclin D1 (CCND1) and cyclin E1 (CCNE1). The oncogenic role of FAM83D was also confirmed in vivo. In conclusion, our study demonstrated that FAM83D might exert its oncogenic activity in LUAD by regulating cell cycle, and that it could serve as a novel biomarker and a potential therapeutic target for LUAD.