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The critical roles of N 6 -methyladenosine (m 6 A) modification have been demonstrated by more and more evidence. However, the cross talk of m 6 A and long noncoding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) tumorigenesis is still unclear. Here, this work focused on the functions and molecular mechanism of m 6 A-modified lncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) in NSCLC. Microarray analysis found that lncRNA DLGAP1-AS2 is upregulated in NSCLC cells. Clinical data showed that DLGAP1-AS2 high-expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 overexpression promoted the aerobic glycolysis and DLGAP1-AS2 knockdown suppressed the tumor growth of NSCLC cells. Mechanistically, m 6 A methyltransferase METTL3 enhanced the stability of DLGAP1-AS2 via m 6 A site binding. Moreover, DLGAP1-AS2 interacted with YTHDF1 to enhance the stability of c-Myc mRNA through DLGAP1-AS2/YTHDF1/m 6 A/c-Myc mRNA. In conclusion, our work indicates the functions of m 6 A-modified DLGAP1-AS2 in the NSCLC aerobic glycolysis, disclosing a potential m 6 A-dependent manner for NSCLC treatment.

Purpose: To investigate the prognostic impact of 4L lymph node (LN) dissection in left lung cancer and to analyze the relative risk factors for 4L LN metastasis., Patients and Methods: We retrospectively collected data from 657 patients with primary left lung cancer who underwent surgical pulmonary resection from January 2005 to December 2009. One hundred thirty-nine patients underwent 4L LN dissection (4L D+ group); the other 518 patients did not receive 4L LN dissection (4L D- group). Propensity score weighting was applied to reduce the effects of observed confounding between the two groups. Study end points were disease-free survival (DFS) and overall survival (OS)., Results: The metastasis rate of station 4L was 20.9%, which was significantly higher than those of station 7 (14.0%; P = .048) and station 9 (9.8%; P < .001). Station 4L metastasis was associated with most other LN station metastases in univariate analysis, but only station 10 LN metastasis was an independent risk factor for 4L LN metastasis (odds ratio, 0.253; 95% CI, 0.109 to 0.588; P = .001) in multivariate logistic analysis. The 4L D + group had a significantly better survival than the 4L D - group (5-year DFS, 54.8% v 42.7%; P = .0376; 5-year OS, 58.9% v 47.2%; P = .0200). After allowing potential confounders in multivariate survival analysis, dissection of 4L LN retained its independent favorable effect on DFS (hazard ratio, 1.502; 95% CI, 1.159 to 1.947; P = .002) and OS (hazard ratio, 1.585; 95% CI, 1.222 to 2.057; P = .001). Propensity score weighting further confirmed that the 4L D + group had a more favorable DFS ( P = .0014) and OS ( P < .001) than the 4L D - group., Conclusion: Station 4L LN involvement is not rare in left lung cancer, and dissection of the 4L LN station seems to be associated with a more favorable prognosis as compared with those who did not undergo this dissection.

Objective: To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment., Methods: Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed., Results: EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation., Conclusion: The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.

Objective: To investigate the mRNA and proten expression of coxsackievirus and adenovirus receptor (CAR) in the corresponding normal lung tissue, para-neoplastic tissue and lung cancer tissue, and the correlation of CAR expression with the carcinogenesis as well as the expression difference in various clinicopathologic parameters., Methods: The expression of CAR mRNA and protein in the samples from 32 lung cancer patients was determined by RT-PCR and Western blot, respectively., Results: The expression level of CAR mRNA and protein in normal lung tissue, paraneoplastic tissue and cancer tissue were 1.000 +/- 0.012, 1.048 +/- 0.035, 1.282 +/- 0.072, and 0.902 +/- 0.038, 0.944 +/- 0.042, 1.08 +/- 0.052, respectively, with a statistical significance among the groups (P = 0.022, P = 0.007, P = 0.009, P = 0.027). There was a statistically significant positive correlation between expression of CAR mRNA and that of CAR protein (r = 0.448, P = 0.026). The expression levels of CAR were significantly different among different pathological types (P = 0.012), with a high level of CAR in all 7 bronchiolo-alveolar carcinoma (BAC, P = 0.029). However, there was no statistical significance in other clinicopathologic parameters (P > 0.05), including gender, age, smoking or not, tumor size, with or without lymph node metastasis and TNM stage., Conclusion: The expression of CAR mRNA and protein in cancer tissue samples are significantly higher than that in the normal and paraneoplastic samples, indicating that CAR might play a crucial role in the carcinogenesis. It may become a new potential prognostic marker for lung cancer patients.

Objective: To study the expression and clinical significance of cytokeratin subtypes CK7 and CK20 and thyroid transcription factor-1 (TTF-1) in bronchioloalveolar carcinoma (BAC), and to investigate the value of these factors in identification of the prognosis of BAC., Methods: Eighty-one specimens of BAC resected during operation, 68 of non-mucinous type and 13 of mucinous type, underwent immunohistochemical examination to detect the expression of CK7, CK20, and TTF-1. The value of these 3 factors in the identification of the prognosis of BAC was examined by survival analysis., Results: All specimens showed positive expression of CK7, CK20, and TTF-1. There was no significant differences in CK7 expression rate among different ages, clinical stages, and pathological subtypes (all P > 0.05). Compared with that in the BAC of stage III and that of BAC of non-mucinous type, the CK20 positive rates of the BAC of stage I - II and mucinous type were both significantly higher (chi(2) = 3.928, P < 0.05, and chi(2) = 11.512, P < 0.05). The TTF-1 positive rates of the BAC of stage III and nonmucinous type were significantly higher than those of stage I - II and mucinous type respectively (chi(2) = 7.840, P < 0.05, and chi(2) = 19.497, P < 0.05). There was a statistically significant positive correlation between the expression of CK7 and expression of TTF-1 (r = 0.257, P = 0.021). Univariate analysis showed that the main prognostic factors were TTF-1 expression (P = 0.017), clinical stage (P = 0.000), tumor diameter (P = 0.017) and N stage (P = 0.000). Strata analysis suggested that in the nonmucinous type BAC patients the survival time of those positive for TTF-1 expression was superior to those negative for TTF-1 (P = 0.009); and in the stage III BAC patients the survival time of those positive for TTF-1 was superior to those negative for TTF-1 (P = 0.022). Cox regression analysis suggested that TTF-1 (P = 0.035), TNM stage (P = 0.000), tumor diameter (P = 0.034), and N stage (P = 0.000) were independent factors affecting the prognosis., Conclusion: There is a statistically significant positive correlation between the expression of CK7 and the expression of TTF-1. TTF-1 and CK20 provide a new evidence for the molecular staging of BAC. TTF-1, TNM stage, tumor diameter and N stage are all independent factors affecting the prognosis of BAC.