Junjie Xi

Prognostic Role of Twist, Slug, and Foxc2 Expression in Stage I Non-Small-Cell Lung Cancer After Curative Resection

UNLABELLED By using immunohistochemistry in tissue microarrays of 137 cases, we evaluated the prognostic power of a 3-marker epithelial-mesenchymal transition–related model in patients with stage I non-small-cell lung cancer who underwent radical surgical resection. The Twist/Slug/Foxc2 coexpression model accurately prognosticated these patients and may be helpful in refining current treatment strategy for stage I non-small-cell lung cancer. BACKGROUND Lung cancer is the leading cause of cancer-related death in the world. Only about 60% of patients with stage I non-small-cell lung cancer (NSCLC) can be cured by surgery alone. Current clinical and molecular markers are inadequate prognosticators. We developed a 3-marker model that closely approximates survival probability of patients with stage I NSCLC. METHODS Expression of Twist, Slug, and Foxc2 was assessed by immunohistochemistry in tissue microarrays that contained paired tumor and peritumoral lung tissue from 137 patients who underwent surgical resection for stage I NSCLC. The prognostic value of Twist, Slug, and Foxc2, and the cumulative effects of the 3 markers on survival were evaluated. RESULTS Increased expression of Twist, Slug, and Foxc2 was observed in 38.0%, 18.2%, and 27.7% of primary tumors, respectively. Overexpression of Twist, Slug, and Foxc2 in stage I NSCLC was associated with a worse overall survival (P = .001, P = .002, P < .001, respectively) and correlated with a shorter recurrence-free survival (P < .001, P = .001, P < .001 respectively). The cumulative influence of these markers on outcome was analyzed; a combination of more than 2 positive markers was an independent predictor of recurrence-free and overall survival (P = .002 and P = .009, respectively). CONCLUSIONS The Twist/Slug/Foxc2 model is useful in predicting survival of stage I NSCLC and may be helpful in refining current treatment strategy.

Primary pulmonary mucoepidermoid carcinoma: an analysis of 21 cases

BackgroundThe optimal treatment for pulmonary mucoepidermoid carcinoma (MEC), a rare type of tumor, has not been established yet. This study analyzed the survival of pulmonary MEC patients and attempted to find clues for optimal treatment.MethodsA total of 21 patients with pulmonary MEC from November 2004 to January 2011 were included in the investigation. Immunohistochemistry, epidermal growth factor receptor (EGFR) mutation, and survival were retrospectively studied.ResultsAmong the 21 pulmonary MEC patients, 17 were diagnosed with low-grade malignancy and 4 with high-grade malignancy through pathological examination. The prognosis was found to be poor in the presence of lymph nodes. The expression rates of EGFR and HER2 were 28.6% and 0%, respectively, which correlated with neither grade nor prognosis. The mutation rate of EGFR was 0. Log-rank test results indicated that age, grade, lymph node metastasis, and tumor-node-metastasis stage were prognostic factors.ConclusionAge, grade, lymph node metastasis and tumor-node-metastasis stage correlate with the survival of pulmonary MEC patients.Trial registrationThis study was approved and registered by the Ethics Committee of Zhongshan Hospital. Written informed consent was obtained from all participants prior to treatment.

Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer

In order to identify novel non-invasive biomarkers with high accuracy for the screening of non-small cell lung cancer (NSCLC), we investigated the predictive power of 4 microRNAs (miR-146, miR-204, miR-106a and miR-124) in plasma samples obtained from patients with NSCLC and healthy controls (n=50; training phase) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We found that the levels of miR-204 in the patients with NSCLC were significantly dysregulated compared with the healthy controls, and thus this miRNA was selected for further validation. For the validation phase, RT-qPCR was performed on plasma samples from patients with NSCLC and healthy controls (n=176) in order to examine the expression levels of the candidate miRNA, miR-204. The results revealed that the plasma levels of miR-204 were significantly downregulated in the patients with NSCLC compared with the healthy controls (p<0.001). The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-204 was 0.809 (sensitivity, 76%; specificity, 82%), which was higher than the values obtained for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). The expression of miR-204 in plasma significantly correlated with the tumor stage (p=0.009) and distant metastasis (p=0.048). A log-rank test revealed that lower plasma levels of miR-204 were associated with a shorter overall survival and disease-free survival (p=0.006 and 0.0065, respectively). Both univariate and multivariate Cox regression analyses indicated that a lower miR-204 expression level in plasma was a prognostic factor with a relative risk of death of 1.936 and 1.712, respectively. On the whole, our results suggest that the decreased expression of miR-204 in plasma is a promising biomarker for the detection of NSCLC and the prediction of poor survival in patients with the disease.

Identification of reference miRNAs in human tumors by TCGA miRNA-seq data.

Although the accuracy of detecting the expression of miRNAs by quantitative real-time polymerase chain reaction (qRT-PCR) is highly dependent on reliable reference miRNAs, many commonly used reference miRNAs are not stably expressed and as such are not suitable for quantification and normalization of qRT-PCR data. To solve this problem, we analyzed the global expression profiles of thousands of samples in 14 types of common human tumors released by The Cancer Genome Atlas (TCGA), and identified the most stably and highly expressed miRNAs as candidate reference miRNAs in each type of tumor. We found that miR-361-5p and let-7i-5p were the most recommended candidate reference miRNAs in nine and eight types of tumors, respectively, followed by let-7a-5p, mir-28-5p and miR-99b-5p. Our results are of important value to those researchers focused on miRNA; however, these candidate reference miRNAs still need to be validated prior to their use in qRT-PCR studies.

Landscape of expression profiles in esophageal carcinoma by The Cancer Genome Atlas data.

In this study, we explored the gene and microRNA (miRNA) expressions profile of esophageal carcinoma. The expression data for messenger RNAs and miRNAs in normal and cancerous esophageal tissues were obtained from the Cancer Genome Atlas database and then the differentially expressed genes and miRNAs were identified. As a result, we identified 2962 genes and 45 miRNAs differentially expressed in esophageal carcinoma compared with normal esophageal tissues. Subsequently, the altered gene functions and signaling pathways were investigated using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and these differentially expressed genes were significantly enriched in the cell cycle, cell migration, mitogen-activated protein kinase (MAPK) and toll-like receptor signaling pathway, and so on. Then the regulatory relationships between the differentially expressed miRNAs and genes were examined with Targetscan and Miranda, and the potential target sites of transcription factors (TFs) in the promoter regions of these miRNAs and genes were identified using the TRANSFAC database. Finally the TF-miRNA-gene network in esophageal cancer was established, summarizing the regulatory links among the TFs, differentially expressed miRNAs and differentially expressed genes. Factors such as core promoter-binding protein (CPBP), nuclear factor of activated T-cells 1 (NFAT-1), miR-30c-5p, were located in the central hub of this network, highlighting their vital roles in esophageal tumorigenesis. These findings may extend our understanding of the molecular mechanisms underlying esophageal carcinoma and promote new perspectives for prevention, diagnosis and treatment.

Clinical outcome of subcentimeter non‐small cell lung cancer after surgical resection: Single institution experience of 105 patients

The detection of subcentimeter lung cancers has significantly improved with advances in computed tomography and the emergence of screening protocols. We reviewed the clinicopathological features and surgical outcomes of patients with subcentimeter non‐small cell lung cancer (NSCLC) in our institution.

Uniportal video-assisted thoracic surgery lobectomy in semiprone position: primary experience of 105 cases

BACKGROUND Uniportal video-assisted thoracic surgery (VATS) is becoming popular, and uniportal lobectomy in semiprone position was reported in 2014. This study aimed to investigate the feasibility and safety of uniportal VATS in semiprone position. METHODS From May 28, 2014 to October 19, 2015, we attempted uniportal VATS lobectomy in semiprone position in 105 cases. Forty-five patients were male, and 60 patients were female. Average age was 57.1±10.6 years (24-76 years). Perioperative parameters were documented. RESULTS There were two conversions to three-port lobectomy, one conversion to double-port lobectomy, and three conversions to thoracotomy. Among the patients who received uniportal VATS in semiprone position, mean operation duration was 137.4±47.8 minutes. Mean estimated blood loss was 60.7±102.7 mL. Mean time of drainage was 3.0±2.1 days, and postoperative length of stay averaged 4.9±2.3 days. In the cases of primary lung cancer, the mean number of nodal stations explored was 7.2±1.3, with a mean of 20.8±6.3 lymph nodes resected. As to the mediastinal lymph node specifically, a mean of 4.4±1.0 nodal stations were explored, and the number of resected mediastinal lymph nodes averaged 12.8±5.1. No perioperative death or major complication occurred. CONCLUSIONS Uniportal VATS lobectomy in semiprone position is feasible and safe.

Ground glass opacities: Imaging, pathology and gene mutations

Background Lung cancer can be detected in its early stages with computed tomography (CT). Early lung adenocarcinoma often is displayed as ground glass opacity (GGO), an entity that has been well studied over the past decade. However, few studies have focused on the correlation between CT characteristics and pathologic subtype of GGO. We aimed to explore the correlation between CT characteristics, pathologic subtype, and gene mutation associated with GGO in an effort to aid in the treatment of lung adenocarcinoma. Methods In this retrospective study, patients with GGO who underwent surgery in our institution between 2013 and 2016 were included. Patients were divided into 2 groups on the basis of CT characteristics: group 1, diameter <20 mm and solid component <50%; and group 2, diameter ≥20 mm or solid component ≥50%. Differences in pathologic subtype and gene mutation pattern between groups were compared using the χ2 test. The correlation between pathologic subtype and epidermal growth factor receptor (EGFR) mutation was also tested using the χ2 test. Results A total of 1018 cases (408 in group 1, 610 in group 2) were included; of these, 544 were tested for the EGFR gene mutation. There was a significant difference in predominant subtype (P < .001) and all included subtypes (P = .044) between the groups. Of 59 cases with the pathologic subtype of micropapillary or solid, 57 were in group 2. The EGFR gene mutation rate was significantly higher in group 2 than group 1 (P < .001) and significantly correlated with pathologic subtype (P < .001); adenocarcinoma in situ was the lowest (31.4%) and papillary was the highest (85.7%). EGFR mutation subtype did not significantly differ between groups (P = .499). Conclusions CT characteristics of GGO significantly correlated with pathologic subtype and gene mutation rate. The EGFR mutation rate differed significantly among pathologic subtypes. GGOs with a diameter of <20 mm and with a solid component <50% seldom contain subtypes with poor prognosis (micropapillary and solid) and the EGFR mutation rate was significantly lower.

Quantifying the expression of tumor marker genes in lung squamous cell cancer with RNA sequencing.

BACKGROUND We measured the expression of some commonly used tumor markers with RNA sequencing (RNA-Seq) to identify any that might be useful for the evaluation of squamous cell lung cancer and identify possible correlations between these tumor markers and any clinical characteristics. METHODS RNA-Seq was performed on five pairs of squamous-cell lung cancer and normal tissues and another 39 squamous-cell lung cancer tissues obtained by our department between September and December, 2012. The expression of 13 commonly used tumor markers was determined. RESULTS All of the patients in our study were male. The expressions of CA125, CYFRA21-1, NSE and SCC increased in tumor samples and there were statistically significant differences between squamous cell lung cancer and normal tissues (P=0.008, P<0.001, P<0.001, P=0.001). The expression of β2M and CA15-3 was reduced in squamous cell carcinoma relative to normal tissues and there was no significant difference in the expression of other tumor markers, including AFP, AFU, CT, FER and HE4. CONCLUSIONS CA125, CYFRA21-1, NSE and SCC may be appropriate tumor markers for squamous cell lung cancer.

Stage selection for neoadjuvant radiotherapy in non-cervical esophageal cancer: A propensity score-matched study based on the SEER database: Stage selection for NRT in esophageal cancer

The effect of neoadjuvant radiotherapy (NRT) was controversial in non‐cervical esophageal cancer. The aim of this study was to identify which stage of non‐cervical esophageal cancer would get benefit from NRT using propensity score matching (PSM) and survival analysis based on the Surveillance Epidemiology, and End Results (SEER) database.