Expression of serum exosomal miR-23b-3p in non-small cell lung cancer and its diagnostic efficacy.

The present study aimed to investigate the expression of serum exosomal miR-23b-3p in non-small cell lung cancer (NSCLC) and to determine its diagnostic efficacy for NSCLC. From October, 2017 to October, 2019, 80 patients with NSCLC, 60 patients with pneumonia and 30 healthy subjects undergoing physical examination were enrolled at the People's Hospital of Yangzhong City. Serum samples were collected from the 3 groups of patients. The expression of miR-23b-3p in exosomes was detected by RT-qPCR. The Chi-squared test was used to analyze the expression level of miR-23b-3p in exosomes, and the patients with NSCLC were divided into 2 groups according to the expression level. The association between the patient clinicopathological parameters and receiver operating characteristic (ROC) curves was used to evaluate the diagnostic efficacy of serum exosomal miR-23b-3p in NSCLC. The expression level of serum exosomal miR-23b-3p in the patients with NSCLC was significantly higher than that in patients with pneumonia (t=10.332, P<0.001) and healthy subjects (t=12.810, P<0.001); serum exosomal miR-23b-3p was significantly associated with tumor size, depth of invasion, liver metastasis and TNM stage (P<0.05). The area under the curve (AUC) for miR-23b-3p was 0.915 (95% CI, 0.84-0.92), the optimal relative expression of miR-23b-3p was 3.46, the sensitivity of diagnosis was 87.4%, and the specificity was 93.8%, all higher than that of carcinoembryonic antigen (CEA). The ROCAUC of NSCLC was 0.645 (95% CI, 0.641-0.772) and for Cyfra21-1 it was 0.745 (95% CI, 0.701-0.812). Compared with the patients with pneumonia and the healthy subjects, the patients with NSCLC exhibited a higher level of serum exosomal miR-23b-3p. On the whole, these findings indicate that miR-23b-3p has a higher clinical diagnostic efficacy and may thus be a potential biomarker for the early diagnosis of NSCLC.

Profiles of differentially expressed circRNAs in esophageal and breast cancer.

INTRODUCTION: Circular RNAs (circRNAs) function as efficient microRNA sponges with gene-regulatory potential and are promising cancer biomarkers. In this study, we used the Arraystar Human circRNA Array to construct a genome-wide circRNA profile of esophageal squamous cell cancer (ESCC) and breast cancer (BC). PATIENTS AND METHODS: Expression levels between cancer lesions and adjacent normal-appearing tissues were compared. We observed 469 upregulated circRNAs and 275 downregulated circRNAs in ESCC. Hsa_circRNA_103670 was upregulated 20.3-fold, while hsa_circRNA_030162 was downregulated 12.1-fold. For BC, 715 circRNAs were upregulated, and 440 circRNAs were downregulated. Hsa_circRNA_005230 was upregulated 12.2-fold, while hsa_circRNA_406225 was downregulated 12.4-fold. RESULTS: When we set the criteria as fold change in expression ≥2 between cancer and adjacent normal-appearing tissue with a P-value <0.01, there were 22 common circRNAs (11 upregulated and 11 downregulated) in relation to both ESCC and BC. Gene ontology and the Kyoto encyclopedia of genes and genomes analyses showed that these circRNAs were involved in the tumorigenesis of human cancers. CONCLUSION: Our study revealed that circRNAs are promising candidates as valuable biomarkers for ESCC and BC, although relevant research is still in its infancy and the functional role of specific circRNAs in tumorigenesis is just starting to be elucidated.

Long-term trends and survival analysis of esophageal and gastric cancer in Yangzhong, 1991-2013.

OBJECTIVE: To describe the long-term trends of the incidence, mortality and survival of upper digestive tract cancers in a high-risk area of China. METHODS: We extracted esophageal and gastric cancer cases diagnosed from 1991 to 2013 through the Yangzhong Cancer Registry and calculated the crude and age-standardized incidence and mortality rates. Cancer trends were calculated using the Joinpoint Regression Program and were reported using the annual percentage change (APC). The cancer-specific survival rates were evaluated and compared between groups using the Kaplan-Meier method and log-rank test. RESULTS: The age-standardized incidence rate of esophageal cancer declined from 107.06 per 100,000 person-years (male: 118.05 per 100,000 person-years; female: 97.42 per 100,000 person-years) in 1991 to 37.04 per 100,000 person-years (male: 46.43 per 100,000 person-years; female: 27.26 per 100,000 person-years) in 2013, with an APC of -2.5% (95% confidence interval (CI): -3.4%, -1.5%) for males and -4.9% (95% CI:-5.8%, -3.9%) for females. The age-standardized incidence rate of gastric cancer was 165.11 per 100,000 person-years (male: 225.39 per 100,000 person-years; female: 113.34 per 100,000 person-years) in 1991 and 53.46 per 100,000 person-years (male: 76.51 per 100,000 person-years; female: 32.43 per 100,000 person-years) in 2013, with the APC of -3.6% (95% CI: -4.5%, -2.7%) for males and -4.8% (95% CI: -5.7%, -3.9%) for females. The median survival time was 3.0 years for patients with esophageal or gastric cancer. Cancer cases detected after 2004 had a better prognosis. CONCLUSIONS: The age-standardized incidence rates of both esophageal and gastric cancer continuously decreased since 1991 through 2013, whereas the mortality rate remained stable before 2004 and significantly declined following the massive endoscopic screening program initiated in 2004. The survival probability of patients with esophageal and gastric cancer has improved obviously in recent decades.

Accumulated promoter methylation as a potential biomarker for esophageal cancer.

We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965-1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928-1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.

Massive Endoscopic Screening for Esophageal and Gastric Cancers in a High-Risk Area of China.

OBJECTIVE: This study aims to describe the findings from a massive endoscopic screening program in a high-risk area of China and to evaluate the prognosis of patients diagnosed through endoscopic screening compared with those diagnosed at usual hospital visits because of illness. METHODS: In 2006, an early detection and treatment program was initiated in Yangzhong county, China. Local residents aged 40-69 years were eligible for free endoscopic screening. Endoscopic examination was performed with Lugol's iodine staining, followed by biopsies. Patients diagnosed with esophageal or gastric cancer were referred for treatment and followed to assess their long-term survival status. RESULTS: From 2006 through 2012, we screened 12453 participants, including 5334 (42.8%) men and 7119 (57.2%) women. The average age was 52.8 ± 8.0 years. We detected 166 patients with upper digestive tract cancers, including 106 cancers in the esophagus (detection rate: 0.85%) and 60 cancers in the stomach (detection rate: 0.48%). Of these patients, 98.11% with esophageal cancer and 100% with gastric cancer were defined as at the early stage. In the process of follow-up, 17 patients died from cancer-related causes, and the median survival time was greater than 85 months. The overall survival rates for 1, 3 and 5 years were 98.0%, 90.0% and 89.0%, respectively. A significant positive effect was observed for the long-term survival of patients diagnosed through massive endoscopic screening. CONCLUSIONS: In a high-risk population, massive endoscopic screening can identify early stage carcinoma of esophageal and gastric cancers and improve patients' prognosis through early detection and treatment.

Interaction between XRCC1 polymorphisms and intake of long-term stored rice in the risk of esophageal squamous cell carcinoma: a case-control study.

OBJECTIVE: This study aimed to explore the roles of three common single nucleotide polymorphisms in the X-ray repair cross-complementing group-1 gene (XRCC1) and of life style factors and their possible interactions in the risk of esophageal squamous cell carcinoma (ESCC) in China. METHODS: A population-based case-control study of 432 cases and 915 controls was conducted in Yangzhong County, Jiangsu Province, China. Subjects were interviewed by trained interviewers using a structured questionnaire that included questions on demographics and life style. XRCC1 genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay. Unconditional logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations of ESCC with XRCC1 polymorphisms and lifestyle-related factors. RESULTS: Both the drinking of river water and alcohol intake history were significantly associated [SW1]with an increased risk of ESCC among men with aORs of 4.20 (95% CI: 2.90-6.07) and 2.03 (95% CI: 1.43-2.89), respectively. For women, the corresponding odds ratios were 8.37 (95% CI: 5.09-13.75) for river water drinking and 12.78 (95% CI: 2.69-60.69) for long-term stored rice intake. After the XRCC1 G28152A polymorphism was adjusted for potential confounders, subjects with GA and AA genotypes had an increased risk for ESCC (aOR: 1.21, 95% CI: 0.93-1.56), compared with subjects with a GG genotype, and a positive multiplicative interaction between intake of long-term stored rice and the XRCC1 G28152A polymorphism was observed (P=0.009). CONCLUSIONS: Our findings suggest that both lifestyle-related factors, including drinking river water, long-term stored rice and alcohol intake, and the XRCC1 G28152A polymorphism were possible risk factors for ESCC, and that the XRCC1 G28152A polymorphism modified the effect of long-term stored rice intake on the risk of ESCC among Chinese people.

[Analysis of the therapeutic effect of esophagectomy with extended 2-field lymph node dissection for esophageal carcinoma].

OBJECTIVE: To summarize the surgical effect and clinical application value of esophagectomy with extended 2-field lymph node dissection for patients with esophageal carcinoma. METHODS: From June 1987 to December 2008, 1690 patients with esophageal cancer underwent esophagectomy with extended 2-field (thoracic and abdominal) dissection of lymph nodes. Patients with the middle and lower thoracic esophageal cancer underwent Ivor-Lewis esophagectomy, and patients with upper thoracic esophageal cancer underwent Akiyama esophagectomy. 2-field (thoracic and abdominal) lymph node metastases information and the 1, 3, 5, 10-year survival rates were analyzed retrospectively. RESULTS: Lymph node metastases were found in 713 patients. The lymph node metastases rate was 42.2% (713/1690).Thoracic lymph node metastasis rate was 39.3% (665/1690), among which in the right pleural apical para-tracheal triangle was 20.7% (349/1690), in the posterior upper mediastinum was 26.3% (444/1690), in the lower mediastinum was 18.2% (307/1690). Abdominal lymph node metastasis rate was 20.1% (339/1690). THE Postoperative complication rate was 16.4% (278/1690), among which the pulmonary complication rate ranking the first, was 43.6% (136/312). The operative mortality rate was 0.2%. The 1-year, 3-year, 5-year and 10-year survival rates were 88.2% (1388/1574), 63.5% (868/1367), 54.8% (705/1287) and 30.8% (232/754), respectively. The 5-year survival rate in patients without lymph node metastasis was 76.2% (448/588), but that in patients with lymph node metastases was 36.8% (257/669). CONCLUSION: The results of this study demonstrated that Ivor-Lewis and Akiyama esophagectomy with two-field lymph node dissection exposes the operation fields clearly and make radical lymphadenectomy thoroughly, especially the lymph nodes in the posterior upper mediastinum around the recurrent laryngeal nerve and in the right pleural apical para-tracheal triangle. It is essential that patients with esophageal carcinoma with lymph node metastases should undergo esophagectomy with extended 2-field dissection of lymph nodes. This can elevate the postoperative 5-year survival rate remarkably.

FAS and FAS ligand polymorphisms in the promoter regions and risk of gastric cancer in Southern China.

The FAS and FAS ligand (FASLG) system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumorigenesis. Functional promoter polymorphisms of the FAS and FASLG genes can alter transcriptional activities and thus alter risk of cancer. We hypothesized that the FAS -1377G>A, FAS -670A>G, and FASLG -844T>C polymorphisms in the promoter regions are associated with risk of gastric cancer. In a population-based case-control study of 332 gastric cancer cases and 324 controls, we genotyped these three polymorphisms and evaluated their association with risk of gastric cancer. We found that the FAS and FASL genotypes and the FAS haplotypes had no significant associations with risk of gastric cancer. In addition, there was no significant interaction between the FAS and FASL polymorphisms in the development of gastric cancer. The FAS and FASLG polymorphisms may not contribute to risk of gastric cancer in the southern Chinese population.

FAS promoter polymorphisms and cancer risk: a meta-analysis based on 34 case-control studies.

FAS is a cell surface receptor involved in apoptotic signal transmission and plays important roles in the etiology of cancer. The -1377G>A and -670A>G polymorphisms of the FAS gene influence the FAS transcription and have been implicated in cancer risk. However, the results from the published studies on the association between these two FAS polymorphisms and cancer risk are conflicting. To derive a more precise estimation of association between the FAS polymorphisms and risk of cancer, we performed a meta-analysis of 11 461 cancer cases and 12 708 controls from 34 published case-control studies for these two polymorphisms. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the -1377AA genotype were associated with higher cancer risk than those with the -1377GG (OR = 1.21, 95% CI: 1.08-1.36, P(heterogeneity) = 0.062) or GA/GG (OR = 1.23, 95% CI: 1.10-1.36, P(heterogeneity) = 0.060) genotypes, whereas the -670GG genotype had no effects on overall cancer risk. In the stratified analyses for the -1377G>A polymorphism, there was a significantly increased risk of breast cancer but a significantly decreased risk of melanoma in a dominant model. Moreover, a significantly increased risk was observed among smokers in a recessive model (OR = 1.96, 95% CI: 1.55-2.49; P(heterogeneity) = 0.528). Although some modest bias could not be eliminated, this meta-analysis suggested that the FAS -1377A allele is a low-penetrant risk factor for cancer development, particularly among smokers.

[Correlation of aberrant methylation of MGMT gene to MTHFR C677T genetic polymorphisms in esophageal squamous cell carcinoma].

BACKGROUND & OBJECTIVE: As one of the principal causes of gene inactivation, aberrant hypermethylation in the promoter of cancer-related genes has attracted more and more attention. However, such studies on esophageal cancer are still limited. This study was to investigate the association between aberrant hypermethylation of MGMT gene and clinical characteristics as well as MTHFR C677T genetic polymorphisms in esophageal squamous cell carcinoma in a Chinese population. METHODS: A molecular epidemiologic study was conducted at Yangzhong County, Jiangsu Province of China, on histologically confirmed esophageal squamous cell carcinoma patients who were operated in the People's Hospital of Yangzhong County between January 2005 and March 2006. Peripheral blood samples, esophageal cancer tissues and paracancerous normal tissues were collected. Methylation-specific polymerase chain reaction(MSP) was used to detect the CpG island methylation status of MGMT gene. Restrictive fragment length polymorphism (RFLP) technique was used to test polymorphisms of folate metabolism enzyme gene MTHFR. The association between methylation status of MGMT gene and clinical characteristics as well as MTHFR C677T polymorphisms were analyzed. RESULTS: Among 125 esophageal squamous cell carcinoma patients, the aberrant hypermethylation rate of MGMT gene was 27.2% in cancer tissues and 11.2% in paracancerous normal tissues. No hypermethylation was found in normal esophageal tissues from 10 healthy adult subjects. Methylation rate of MGMT gene in cancer tissues was significantly higher in the patients with lymph node metastasis than in those without lymph node metastasis (37.3% vs. 18.2%, P=0.017). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol drinking and green tea drinking. After adjusting by potential confounders, variant allele of MTHFR C677T was found to be associated with hypermethylation of MGMT gene. Compared with wild type CC, the odds ratio was 3.34 (95% CI: 1.07-10.39) for CT and 3.83 (95% CI: 1.13-12.94) for TT. CONCLUSION: Aberrant CpG island hypermethylation of MGMT gene is closely related with the genesis and progression of esophageal squamous cell carcinoma.

Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma.

To explore the role of aberrant hypermethylation of cancer-related genes, such as P16, MGMT, and hMLH1, in the esophageal squamous cell carcinoma (ESCC) as well as its relation to dietary folate intake and MTHFR C677T polymorphism, we conducted a molecular epidemiologic study in China. One hundred and twenty-five histologically confirmed ESCC patients having undergone surgery in the Yangzhong People's Hospital between January 2005 and March 2006 were recruited. The aberrant CpG island hypermethylation of P16, MGMT, and hMLH1 genes could be found in cancer tissues with frequency of about 88.0%, 27.2%, and 3.2%, respectively, and in remote normal-appearing esophageal tissues with frequency of about 36.8%, 11.2%, and 0.0%, respectively. No hypermethylation was found in the normal esophageal tissues from healthy controls. Compared with those patients without lymph node metastasis, MGMT gene showed a higher proportion of hypermethylation in cancer tissues, whereas P16 gene showed a higher proportion of hypermethylation in remote normal-appearing esophageal tissues in patients with lymph node metastasis. A significant association was found between MTHFR C677T genetic polymorphism and CpG island methylation status of MGMT gene. After adjustment for potential confounders, individuals carrying CT or TT genotype have higher frequency of hypermethylation in MGMT gene in cancer tissues, with odds ratio of 3.34 (95% confidence interval, 1.07-10.39) and 3.83 (95% confidence interval, 1.13-12.94), respectively. This study indicated that the aberrant CpG island hypermethylation of cancer-related genes was associated with ESCC and might be a promising biomarker in diagnosis and prognosis.

[Right para-tracheal triangle lymphadenectomy for esophageal carcinoma].

OBJECTIVE: To investigate the incidence of lymph node metastasis (LNM) in the right para-tracheal triangle (RPT) of esophageal carcinoma patients and the technique of dissection. METHODS: On the top of double mediastinal and abdominal lymphadenectomy, 333 esophageal carcinoma patients received RPT lymphadenectomy through the right pleural apical approach from 1990 to 2001. RESULTS: In these 333 patients, the lymph node metastasis (LNM) rate in the RPT was 36.40%. A total of 457 nodes among 2 159 nodes removed gave a metastasis degree of 24.96%. The LNM rates in RPT for cervical, upper third, middle third, and lower third segments of esophagus were 66.67%, 45.45%, 34.19% and 15.79% (P < 0.05), while their respective metastasis degrees were 44.44%, 27.04%, 24.32% and 18.92% (P > 0.05). The frequency of positive nodes in the RPT for PTI, PT1, PT2, PT3 and PT4 was 0, 17.24%, 28.7%, 45.16% and 53.57%, while those of metastasis degree were 0, 8.77%, 17.62%, 33% and 41.17% (P < 0.01). The frequency of LNM in the RPT in papillary, erosive, patch-like and covert type of early tumor was 40%, 3.85%, 0 and 0 (P < 0.05), while those of the metastasis degree were 29.41%, 1.82%, 0 and 0 (P < 0.01). Higher rate of LNM in progressive stenotic esophageal carcinoma was observed compared with those of the other gross types (56.52%, P < 0.05), so was the degree (P < 0.01). The frequency of LNM in the RPT for mono-focal and multi-focal tumor was 34.98% and 70% without significant difference (P > 0.05), while the degree was 24.29% and 53.33% (P < 0.05). Postoperative complications were: leak (0.6%), and recurrent laryngeal nerve injury (1.2%). No injury of vein or infra-clavicular artery, tracheal damage or mortality occurred. CONCLUSION: 1. The lymph node metastasis from esophageal carcinoma has a tendency of wide spread and right para-tracheal triangle is an important region to be doomed. 2. With location, depth of tumor invasion and differentiation of tumor as major factors affecting LNM of esophageal carcinoma, dissection of this region should be paid more emphasis. 3. In early lesions, higher frequency of LNM in the RPT is found in papillary and erosive lesions than in the other macroscopic types. 4. Exposing the RPT, lymph node by dissection through a right pleural apical approach is very important and significant.