Association of human XPA rs1800975 polymorphism and cancer susceptibility: an integrative analysis of 71 case-control studies.

BACKGROUND: The objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A (XPA) gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence. METHODS: We retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case-control studies for pooled assessment. P-values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg's test and Egger's test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses. RESULTS: In total, 71 case-control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (P < 0.05, OR > 1). A similar positive conclusion was also detected in the "skin cancer" or "skin basal cell carcinoma (BCC)" subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes of XPA in the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (P < 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (P < 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between the XPA rs1800975 A/G polymorphism and the risk of lung or colorectal cancer. CONCLUSIONS: Our findings provide evidence of the close relationship between the XPA rs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect of XPA rs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.

LINC01419 promotes cell proliferation and metastasis in lung adenocarcinoma via sponging miR-519b-3p to up-regulate RCCD1.

Lung adenocarcinoma (LUAD) is one of the most common type of lung cancer notorious for the high incidence and mortality around the world. Long non-coding RNAs (LncRNAs) are defined as a class of RNAs with length more than 200 nucleotides. Mounting studies have proved that lncRNAs are related closely to incidence of diseases and play crucial roles in cancer progression. Although LINC01419 has been studied in several cancers, the function and mechanism of LINC01419 in LUAD remains a mystery. Our findings showed that LINC01419 level was high in LUAD cells, and LINC01419 knockdown inhibited carcinogenesis via suppressing cell proliferation, migration as well as invasion. Moreover, bioinformatics prediction, luciferase reporter experiments and RIP assay were used to confirm miR-519-3p was sequestered and negatively regulated by LINC01419. Subsequently, RCCD1 was identified as a miR-519b-3p target and had inverse relationship with miR-519b-3p. LINC01419 was positively related to RCCD1. Furthermore, rescue assays confirmed that miR-519b-3p inhibitor or RCCD1 overexpression could neutralize the effect of LINC01419 silenced in cell proliferation, migration and invasion. Taken together, all the results indicated that LINC01419 exhibited oncogenic behaviors LUAD via binding to miR-519b-3p to enhance the expression of RCCD1, manifesting the underlying therapy values of LINC01419 in LUAD.

Non-small cell lung cancer: miR-30d suppresses tumor invasion and migration by directly targeting NFIB.

OBJECTIVE: To evaluate the role and the molecular mechanism of miR-30d in non-small cell lung cancer (NSCLC). RESULTS: qRT-PCR was used to detect miR-30d expression in NSCLC tissues and cell lines. miR-30d was frequently down-regulated in NSCLC and its expression was associated with clinicopathological features of NSCLCC patients. Over-expression of miR-30d notably inhibited cell migration and invasion in NSCLC cell lines. miR-30d could negatively regulate Nuclear factor I B (NFIB) by directly targeting its 3'-UTR, which was confirmed by luciferase assay. NFIB also reversed miR-30d-mediated suppression on the migration and invasion in NSCLC cell lines. CONCLUSION: miR-30d suppressed cell migration and invasion by directly targeting NFIB in NSCLC, and NFIB could partially abrogated the inhibition of biological functions by miR-30d.

Investigation on Potential Correlation Between Small Nuclear Ribonucleoprotein Polypeptide A and Lung Cancer.

SNRPA (small nuclear ribonucleoprotein polypeptide A) gene is essential for the pre-mRNA splicing process. Using the available datasets of TCGA or GEO, we aimed at exploring the potential association between the SNRPA gene and lung cancer by several online tools (such as GEIPA2, MEXPRESS, Oncomine) and bioinformatics analysis software (R or GSEA). SNRPA was highly expressed in the tissues of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma tissue (LUSC), compared with control tissues. The high SNRPA expression was associated with a poor survival prognosis of LUAD cases, while the genetic alteration within SNRPA was linked to the overall survival prognosis of LUSC cases. There was a potential correlation between promoter methylation and the expression of SNRPA for LUAD. Compared with normal tissues, we observed a higher phosphorylation level at the S115 site of SNRPA protein (NP_004587.1) (p = 0.002) in the primary LUAD tissues. The potential ATR kinase of the S115 site was predicted. Besides, SNRPA expression in lung cancer was negatively correlated with the infiltration level of M2 macrophage but positively correlated with that of Follicular B helper T cells, in both LUAD and LUSC. The enrichment analysis of SNRPA-correlated genes showed that cell cycle and ubiquitin mechanism-related issues were mainly observed for LUAD; however, RNA splicing-related cellular issues were mainly for LUSC. In summary, the SNRPA gene was identified as a potential prognosis biomarker of lung cancer, especially lung adenocarcinoma, which sheds new light on the association between the spliceosomal complex component and tumorigenesis.

Incidence and risk of hepatic toxicities associated with anaplastic lymphoma kinase inhibitors in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Two anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) have been approved for the treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC). Severe hepatotoxicity has been observed in several clinical studies. We aim to assess the incidence and risk of liver toxicity with these drugs by a systematic review and meta-analysis of clinical trials. MATERIALS AND METHODS: The databases of PubMed, Web of Science and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to January 2017. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models. RESULTS: A total of 1,908 patients from 10 clinical trials were included. The incidences of all-grade aspartate aminotransferase (AST) and alanine transaminase (ALT) elevation were 25.2% (95% CI 17.7-34.7%), and 26.0% (95% CI 17.8-36.3%), respectively. The incidences of high-grade (grade 3 and 4) AST and ALT elevation were 7.0% (95% CI: 5.4-9.0%), and 9.9% (95%CI: 5.6-16.7%), respectively. Sub-group analysis according to ALK-TKIs showed that the incidence of liver toxicities associated with ceritinib was higher than that of crizotinib and alectinib. In comparison with chemotherapy, ALK-TKIs significantly increased the risk of developing all-grade and high-grade AST elevation (RR, 2.30, 95%CI: 1.87-2.83, p < 0.001; RR 10.14, 95% CI: 3.9-26.39, p < 0.001) and ALT elevation (RR 2.37, 95%CI: 1.97-2.86, p < 0.001; RR 7.34, 95% CI: 3.95-13.63, p < 0.001), respectively. CONCLUSIONS: The use of ALK-TKIs significantly increases the risk of developing all-grade and high-grade liver toxicities in lung cancer patients.

Evaluation of short-term and long-term efficacy of surgical and non-surgical treatment in patients with early-stage small cell lung cancer: A comparative study.

OBJECTIVE: The aim of this study is to compare surgery with adjuvant chemoradiotherapy versus non-surgical treatments for patients with early-stage small cell lung cancer (SCLC) based on the short-term and long-term efficacy. METHODS: SCLC patients who underwent a pulmonary lobectomy with post-surgical radiotherapy or chemotherapy were assigned to the surgical group. SCLC patients who received radiotherapy or chemotherapy alone were classified into the non-surgical group. The clinical efficacy was evaluated as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). The total effectiveness rate was calculated as CR + PR. The 1-, 3-, and 5-year survival rates of the two groups were compared. RESULTS: Compared with the non-surgical group, the CR rate and the total effectiveness rate were higher in the surgical group, and the total effectiveness rate for male patients and patients without a smoking history were also higher in the surgical group. Distant metastasis and local recurrence concurrent with distant metastasis in the surgical group were both lower in the surgical group than in the non-surgical group. Compared with the non-surgical group, the local recurrence in male patients was lower in the surgical group, and patients in the surgical group had lower distant metastasis at TNM stage IIb. The 1-, 3-, and 5-year survival rates were higher in the surgical group than in the non-surgical group. CONCLUSIONS: These findings indicate that for patients with early-stage SCLC, better scores in effectiveness rate, disease progression, and 1-, 3-, and 5-year survival rates were observed in patients who underwent surgery followed by adjuvant chemoradiotherapy when compared with patients without surgical treatment.