Association of NAT-2 gene polymorphisms toward lung cancer susceptibility and prognosis in North Indian patients treated with platinum-based chemotherapy

Aim: The present study has been carried out to evaluate the association of the N-acetyl transferase 2 ( NAT2) variants in North Indian lung cancer patients and healthy controls. Furthermore, we have also determined the effect of the polymorphic variants of the NAT2 gene on the clinical outcomes and overall survival among lung cancer (LC) subjects treated with platinum-based doublet chemotherapy. Methods: This case-control study comprised a total of 550 cases and 550 healthy controls. The genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and the statistical analysis was carried out using MedCalc. Results: There was a lack of any significant association for both 590G>A and 803A>G polymorphisms toward risk for LC, but 857G>A polymorphism exhibited a risk toward LC (p = 0.005). Whereas, variant alleles for the 481C>T polymorphism had a decreased risk for LC (p = 0.0003). Further, 857G>A polymorphism conferred a positive association between genotype and ADCC (p = 0.001) and 481C>T polymorphism had a decreased risk for SQCC (OR = 0.39, p = 0.0006) and SCLC (p = 0.001) subjects. The smokers carrying mutant genotype for the 481C>T polymorphism had a decreased risk toward LC (p < 0.0001) even in light (p = 0.002) as well as heavy smokers (p = 0.001). In case of females, 2.59-fold and 3.66-fold increased risk of LC development was observed in subjects with intermediate and slow acetylator for the 857G>A polymorphism. Whereas, in case of males this polymorphism depicts a reduced risk for LC. On the other hand, 803A>G depicted a 2.82-fold risk of LC in case of female subjects who were slow acetylators. Our study exhibits a significant difference in the overall haplotype distribution between cases and controls. In our study overall, (857G>A, 481C>T, 803A>G) was found to be best model, but was not significant using MDR. Considering the CART results 481C>T polymorphism came out to be the most significant factor in determining the LC risk. For the 803A>G polymorphism, a threefold odds of lymph node invasion were observed for mutant genotype, the recessive model exhibited an odd of 2.8. 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy as the survival time for such patients was better. Conclusion: These results suggest that NAT2 variant genotype for 590G>A and 803A>G was not found to modulate risk toward LC, but 857G>A polymorphism exhibited a risk toward LC and 481C>T polymorphism had a decreased risk for LC. NAT2 590G>A appears to be a potential prognostic factor for OS of SCLC patients after irinotecan therapy and 481C>T came out to be significant factor using CART.

BRAF V600E Mutation in Triple-Negative Breast Cancer: A Case Report and Literature Review

<b><i>Background:</i></b> The B-Raf proto-oncogene (BRAF^V600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAF^V600E mutant breast cancer (BC) has been reported. <b><i>Case Presentation:</i></b> We reported a 60-year-old woman with confirmed triple-negative BC with BRAF^V600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAF^V600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. <b><i>Conclusions:</i></b> The BRAF^V600E mutation may be a potential prognostic factor and therapeutic target for BC.

Genetic polymorphisms in the mEH gene in relation to tobacco smoking: role in lung cancer susceptibility and survival in north Indian patients with lung cancer undergoing platinum-based chemotherapy

Aim: Epoxide hydrolase is involved in oxidative defenses and is responsible for the activation of carcinogens. The relationship between EPHX1 polymorphisms (Tyr113His and His139Arg) and overall survival (OS) and lung cancer (LC) risk was investigated. Methods: The study comprised 550 cases and 550 controls. Genotyping and statistical analysis were applied. Results: The variant genotypes of EPHX1 polymorphisms exhibited no association with LC risk. The Tyr113His polymorphism exhibited twofold increased odds of lymph node invasion (p = 0.04). The Tyr/His genotype is a risk factor for smokers. Subjects carrying the combined genotype for His139Arg showed better median survival time (MST) and the heterozygous genotype revealed better MST in the case of small-cell lung cancer (SCLC; 11.30 vs 6.73 months; log-rank test: p = 0.02). The heterozygous genotype (His139Arg) had longer MST in patients receiving cisplatin/carboplatin and irinotecan (11.30 vs 7.23; log-rank test: p = 0.007) Conclusion: The Tyr113His polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS in patients with SCLC after irinotecan.

The Clinicopathological and Prognostic Significance of SOX9 Expression in Gastric Cancer: Meta-Analysis and TCGA Analysis

BackgroundThe clinicopathological and prognostic significance of SRY-box transcription factor 9 (SOX9) expression in gastric cancer (GC) patients is still controversial. Our aim is to investigate the clinicopathological and prognostic value of SOX9 expression in GC patients.MethodsA systemic literature search and meta-analysis were used to evaluate the clinicopathological significance and overall survival (OS) of SOX9 expression in GC patients. The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between SOX9 expression and OS of stomach adenocarcinoma (STAD) patients.ResultsA total of 11 articles involving 3,060 GC patients were included. In GC patients, the SOX9 expression was not associated with age [odds ratio (OR) = 0.743, 95% CI = 0.507–1.089, p = 0.128], sex (OR = 0.794, 95% CI = 0.605–1.042, p = 0.097), differentiation (OR = 0.728, 95% CI = 0.475–1.115, p = 0.144), and lymph node metastasis (OR = 1.031, 95% CI = 0.793–1.340, p = 0.820). SOX9 expression was associated with depth of invasion (OR = 0.348, 95% CI = 0.247–0.489, p = 0.000) and TNM stage (OR = 0.428, 95% CI = 0.308–0.595, p = 0.000). The 1-year OS (OR = 1.507, 95% CI = 1.167–1.945, p = 0.002), 3-year OS (OR = 1.482, 95% CI = 1.189–1.847, p = 0.000), and 5-year OS (OR = 1.487, 95% CI = 1.187–1.862, p = 0.001) were significantly shorter in GC patients with high SOX9 expression. TCGA analysis showed that SOX9 was upregulated in STAD patients compared with that in normal patients (p &lt; 0.001), and the OS of STAD patients with a high expression of SOX9 is poorer than that in patients with low expression of SOX9, but the statistical difference is not obvious (p = 0.31).ConclusionSOX9 expression was associated with the depth of tumor invasion, TNM stage, and poor OS of GC patients. SOX9 may be a potential prognostic factor for GC patients but needs further study.Systematic Review RegistrationPROSPERO, ID NUMBER 275712.

Asparaginase Like 1 Predicts Unfavourable Prognosis and Facilitates Gastric Cancer Progression Through Inhibits GSK3-β

Background:ASRGL1 plays critical roles in various biological processes and pathologic conditions,including cancer. However, the prognostic importance and biologic functions of ASRGL1 in gastric cancer (GC) are still unclear.Methods:qRT-PCR, western blot and immunohistochemistry analyses were used to determine ASRGL1 expression in GC samples and cell lines. The clinical significance of ASRGL1 was assessed in 100 patients with GC. A series of functional experiments were performed to explore the role and molecular mechanism of ASRGL1 on GC progression. Results:ASRGL1 was upregulated in GC tissues and cell lines. High ASRGL1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes and recurrence of GC patients. Moreover, silencing ASRGL1 in AGS cells significantly inhibited cell proliferation, migration, invasion, whereas overexpression of ASRGL1 significantly enhanced the above abilities of BGC-823 cells. Further mechanism study indicated that these phenotypic changes were mediated by PI3K/AKT and WNT signaling. Finally, we proved that ASRGL1 exerted its tumor-promoting effect by interacting with GSK3-β.Conclusions:ASRGL1 is up regulated in gastric cancer, while it promotes the GC cell proliferation, migration and invasion via interacting with GSK3-β . At the same time it also serves as a potential prognostic factor in patients with GC. ASRGL1 can be used as a new target for diagnosis and treatment of gastric cancer.

Autophagy Markers p62, LC3II and Beclin1 Correlate with Clark Levels in Melanoma Tumors

BackgroundThe prognosis of melanoma depends on early diagnosis and timely treatment. Autophagy as a mechanism of degradation/recycling of cellular debris, has potential to be evaluated as prognostic biomarker in current research. MethodsIn this study, ATG5 and Beclin 1 gene expression in different Clark levels of melanoma were evaluated in a retrospective study of 10 years in the cancer institute of Tehran, Iran. The autophagy activity and the correlation with clinicopathological data were also investigated in a tissue microarray series of 52 melanomas after immunohistochemical staining for the autophagy-associated proteins p62, LC3II and Beclin1. The possibility of autophagy biomarkers were assessed by ROC curve analysis.ResultsThe patterns of ATG5 and Beclin1 gene expression are different. While ATG5 was increased in the early stage and then decreased as the stage was progressed in comparison to tumor margin, the Beclin1 expression was decreased and not altered during tumor progression. However, Beclin1 expression at the protein level was increased with tumor progression. The expression of LC3II was also raised while the p62 levels were declined as the tumor progressed, suggesting an increased autophagy activity in melanoma patients. Melanoma ulceration was positively correlated with Beclin 1 and LC3II expression and inversely correlated with p62 (p<0.05). Autophagy markers expression did not significantly correlate with melanoma mitotic rate and thickness. ConclusionsAutophagy is a potential prognostic factor in the early stage of melanoma and could be considered as a therapeutic target.