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Background: Reduced DNA repair capacity in nucleotide excision repair (NER) pathways owing to genetic variant may influence cancer susceptibility. According to published studies, variants of NER genes associations with colorectal cancer (CRC) risk were inconclusive. Thus, this meta-analysis aimed to explore the possible association. A trial sequence analysis (TSA) analysis was performed to control the risk of false positive or false negative.Methods: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Network (CNKI), Wanfang Database and Scientific and Technical Journal Database (VIP) were searched to identify relative studies until April 2022. The association was assessed by odds ratio (OR) in Allele, homozygous, heterozygous, dominant, recessive, and over-dominant models. In addition, Begg’s and Egger’s tests, sensitivity analysis, subgroup analysis and TSA analysis were performed.Results: A total of 29 studies were eventually included in the meta-analysis, including 12,153 CRC patients and 14,168 controls. It showed that excision and repair cross complementary group 1 (ERCC1) rs11615 CC genotype decreased the risk of CRC, compared with TT genotype (CC vs. TT: OR = 0.816, 95% CI = 0.673–0.990, p = 0.039). For ERCC1 rs3212986, the significant impact was detected on increased the risk of CRC in the allele (OR = 1.267, 95% CI = 1.027–1.562, p = 0.027), homozygous (OR = 1.805, 95% CI = 1.276–2.553, p = 0.001), dominant (OR = 1.214, 95% CI = 1.012–1.455, p = 0.037) and recessive (OR = 1.714, 95% CI = 1.225–2.399, p = 0.002) models, especially in the Asian population. The results revealed the association of ERCC2 rs1799793 A allele with a higher risk of CRC (A vs. G: OR = 1.163, 95% CI = 1.021–1.325, p = 0.023). It also showed that ERCC5 rs17655 increased CRC risk in the allele (OR = 1.104, 95% CI = 1.039–1.173, p = 0.001), homozygous (OR = 1.164, 95% CI = 1.018–1.329, p = 0.026), heterozygous (OR = 1.271, 95% CI = 1.018–1.329, p < 0.001), dominant (OR = 1.241, 95% CI = 1.135–1.358, p < 0.001) and over-dominant (OR = 0.828, 95% CI = 0.762–0.900, p < 0.001) models, especially among Asians.Conclusion: This meta-analysis based on current evidence suggests that the significant association was observed between ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs1799793, and ERCC5 rs17655 and CRC susceptibility. However, given the limited sample size and the influence of genetic background, studies of a larger scale and well-designed are required to confirm the results.

The lack of a useful biomarker partly contributes to the increased mortality of non-small cell lung cancer (NSCLC). MiRNAs have become increasingly appreciated in diagnosis of NSCLC. In the present study, we used microarray to screen 2,549 miRNAs in serum samples from the training cohort (NSCLC, n = 10; the healthy, n = 10) to discover differentially expressed miRNAs (DEMs). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was applied to validate the expression level of selected overexpressed DEMs of NSCLC in a validation cohort (NSCLC, n = 30; the healthy, n = 30). Area under the receiver operating characteristic curve (AUC) was performed to evaluate diagnostic capability of the DEMs. The expression of the miRNAs in tissues was analyzed based on the TCGA database. Subsequently, the target genes of the miR-4687-3p were predicted by TargetScan. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were tested by R software (ClusterProfiler package). NSCLC cells were transfected with inhibitor or mimic to down-regulate or up-regulate the miR-4687-3p level. The function of miR-4687-3p on proliferation, invasion, and migration of lung cancer cells were investigated through CCK-8 and Transwell assays, respectively. In the results, we identified serum miR-4687-3p that provided a high diagnostic accuracy of NSCLC (AUC = 0.679, 95%CI: 0.543–0.815) in the validation cohort. According to the TCGA database, we found that the miR-4687-3p level was significantly higher in NSCLC tissues than in normal lung tissues (p < 0.05). GO and KEGG pathway enrichment analysis showed that postsynaptic specialization and TGF-β signaling pathway were significantly enriched. Down-regulation of miR-4687-3p could suppress the proliferation, invasion, and migration of the NSCLC cells, compared with inhibitor negative control (NC). Meanwhile, overexpression of miR-4687-3p could promote the proliferation, invasion, and migration of the NSCLC cells compared with mimic NC. As a conclusion, our study first discovered that serum miR-4687-3p might have clinical potential as a non-invasive diagnostic biomarker for NSCLC and play an important role in the development of NSCLC.

Karyopherin α2 (KPNA2) was reported to be overexpressed and have unfavorable prognostic effects in many malignancies including hepatocellular carcinoma (HCC). Although its contributions to inflammatory response were reported in many studies, its specific associations with immune infiltrations and immune pathways during cancer progression were unclear. Here, we aimed to identify new markers for HCC diagnosis and prognosis through KPNA2-associated immune analyses. RNA-seq expression data of HCC datasets were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. The gene expressions were counts per million normalized. The infiltrations of 24 kinds of immune cells in the samples were evaluated with ImmuCellAI (Immune Cell Abundance Identifier). The Spearman correlations of the immune infiltrations with KPNA2 expression were investigated, and the specific positive correlation of B-cell infiltration with KPNA2 expression in HCC tumors was identified. Fifteen genes in KEGG (Kyoto Encyclopedia of Genes and Genomes) B-cell receptor signaling pathway presented significant correlations with KPNA2 expression in HCC. Among them, GRB2 and NRAS were indicated to be independent unfavorable prognostic factors for HCC overall survival. Clinical Proteomic Tumor Analysis Consortium HCC dataset was investigated to validate the results at protein level. The upregulation and unfavorable prognostic effects of KPNA2 and GRB2 were confirmed, whereas, unlike its mRNA form, NRAS protein was presented to be downregulated and have favorable prognostic effects. Through receiver operating characteristic curve analysis, the diagnostic potential of the three proteins was shown. The RNA-binding proteins (RBPs) of KPNA2, NRAS, and GRB2, downloaded via The Encyclopedia of RNA Interactomes, were investigated for their clinical significance in HCC at protein level. An eight-RBP signature with independent prognostic value and dysregulations in HCC was identified. All the RBPs were significantly correlated with MKI67 expression and at least one of KPNA2, GRB2, and NRAS at protein level in HCC, indicating their roles in HCC progression and the regulation of the three proteins. We concluded that KPNA2, GRB2, NRAS, and their RBPs might have coordinating roles in HCC immunoregulation and progression. They might be new markers for HCC diagnosis and prognosis predication and new targets for HCC immunotherapy.

Recent reports suggest that microRNAs (miRNAs) may serve as prognostic biomarkers in osteosarcoma. Due to osteosarcoma's early metastasis and poor prognosis, it is very important to find novel prognostic biomarkers for improving osteosarcoma's prognosis. Herein we propose a meta-analysis for serum miRNA's prognostic value in osteosarcoma. In this study, the literature available from PubMed, Web of Science, Embase, and Cochrane Library databases was reviewed. The pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated to evaluate miRNAs prognostic values. A total of 20 studies investigating serum miRNAs were included in this meta-analysis; the initial terminal point of these reports included overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and recurrence-free survival (RFS). For prognostic meta-analyses, the pooled HR for terminal events of higher expression of miRNAs and lower expression of miRNAs were 5.68 (95% CI 4.73–6.82, P < 0.05) and 3.78 (95% CI 3.27–4.37, P < 0.05), respectively. Additionally, subgroup analyses were conducted based on the analysis methods applied and clinicopathological features reported. In the pooled analyses, the miRNA expression levels are associated with poor prognosis according to both univariate and multivariate analyses. Furthermore, serum miRNAs (miRNA-195, miRNA-27a, miRNA-191, miRNA-300, miRNA-326, miRNA-497, miRNA-95-3p, miRNA-223, miRNA-491-5p, miRNA-124, miRNA-101, miRNA-139-5p, miRNA-194) were associated with poor OS and found to be closely correlated with clinical stage and distant metastasis in osteosarcoma. The results illustrate that low or high expression of these specific miRNAs are both potentially useful as prognostic serum biomarkers in osteosarcoma, and miRNAs (miRNA-195, miRNA-27a, miRNA-191, miRNA-300, miRNA-326, miRNA-497, miRNA-95-3p, miRNA-223, miRNA-491-5p, miRNA-124, miRNA-101, miRNA-139-5p, miRNA-194) may indicate clinical stage and metastasis in this form of cancer.

To explore the potential functions and clinical significances of peroxisomes during lung cancer development and progression, we investigated the expressional profiles of peroxisome pathway genes and their correlations with clinical features in non-small cell lung cancer (NSCLC). The RNA-seq data of NSCLC including lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with their clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene expression comparisons between tumor and normal samples were performed with edgeR package in R software and the results of the 83 peroxisome pathway genes were extracted. Through Venn diagram analysis, 38 common differentially expressed peroxisome pathway genes (C-DEPGs) in NSCLC were identified. Principal components analysis (PCA) was performed and the 38 C-DEPGs could discriminate NSCLC tumors from the non-tumor controls well. Through Kaplan-Meier survival and Cox regression analyses, 11 of the C-DEPGs were shown to have prognostic effects on NSCLC overall survival (OS) and were considered as key C-DEPGs (K-DEPGs). Through Oncomine, Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), three K-DEPGs (HSD17B4, ACAA1, and PXMP4) were confirmed to be down-regulated in NSCLC at both mRNA and protein level. Their dy-regulation mechanisms were revealed through their correlations with their copy number variations and methylation status. Their potential functions in NSCLC were explored through their NSCLC-specific co-expression network analysis, their correlations with immune infiltrations, immunomodulator gene expressions, MKI67 expression and their associations with anti-cancer drug sensitivity. Our findings suggested that HSD17B4, ACAA1, and PXMP4 might be new markers for NSCLC diagnosis and prognosis and might provide new clues for NSCLC treatment.