Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt).

The molecular characteristics of lymphoepithelioma-like intrahepatic cholangiocarcinoma (LELCC) remain elusive. We examined 27 LELCC cases through next-generation sequencing using a panel of genes commonly mutated in primary liver cancers. Alterations in BAP1, ARID1A, ARID2, and PBRM1 were detected through immunohistochemistry. Fluorescence in situ hybridization was performed to analyze FGFR2 fusions and CCND1 amplification. LELCC is histologically classified as predominantly undifferentiated or glandular. Epstein-Barr virus-encoded small RNA (EBER) expression was found in 16 LELCCs. Approximately 50% of LELCCs expressed programmed death-ligand 1 strongly. Notably, recurrent pTERT and TP53 mutations were detected in 9 (38%) and 8 (33%) tumors, respectively. Only 2 LELCCs exhibited loss of expression for PBRM1. Alterations in genes typically involved in intrahepatic cholangiocarcinoma, including IDH1, IDH2, ARID1A, ARID2, and BAP1, and FGFR2 fusions, were not identified. The 2-step clustering analysis showed 2 distinct subgroups in LELCC, which were separated by EBER expression. A meta-analysis of all reported cases (n=85) has shown that EBER+ LELCC is strongly associated with the female sex, younger age, and exhibited predominantly glandular differentiation (P=0.001, 0.012, and <0.001, respectively). Patients with EBER- LELCC were more likely to have viral hepatitis and cirrhosis (P=0.003 and 0.005, respectively). Genetic analysis demonstrated that EBER- LELCC was significantly associated with pTERT and TP53 mutations (P=0.033 and 0.008, respectively). In conclusion, LELCC is genetically distinct from intrahepatic cholangiocarcinoma. EBER- LELCC may exhibit a different pathogenesis from EBER+ LELCC. High programmed death-ligand 1 expression in LELCC has implications for potential immunotherapeutic strategies.

The Androgen Receptor Splice Variant 7 (AR-V7) has been associated with poor clinical outcomes in patients with castration-resistant prostate cancer (CRPC). Herein, we performed a meta-analysis aimed at systematically exploring the association between metastatic sites and AR-V7 expression in CRPC patients across prospective clinical trials.

Because of widespread use, understanding the pulmonary effects of cannabis use is important; but its role independent from tobacco smoking is yet to be elucidated. We used Mendelian randomization (MR) to assess the effect of genetic liability to lifetime cannabis use and cannabis use disorder on pulmonary function and lung cancer.

Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0-2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0-1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4-11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% CI 0.86-0.94, p<0.001). Two CNV cut-off points demonstrated a sensitivity and specificity higher than 80%. A cut-off of ≥3 CNVs corresponded to 85% sensitivity and 84% specificity, and a cut-off of ≥4 CNVs corresponded to 81% sensitivity and 91% specificity, respectively. This individual patient data meta-analysis provides a comprehensive overview of CNVs in cutaneous intermediate melanocytic lesions, based on the largest pooled cohort of ambiguous melanocytic neoplasms to date. Our meta-analysis suggests that a cut-off of ≥3 CNVs might represent the optimal trade-off between sensitivity and specificity in clinical practice to differentiate intermediate lesions from melanoma.

Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population.

MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC are still not clear. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC.

To undertake a systematic review and meta-analysis to evaluate the prognostic value of Forkhead box F2 (FOXF2) levels in different types of cancers prone to bone metastasis.

Improper medical use of variant of uncertain significance (VUS) remains a concern in hereditary cancer genetic testing. The goal of this study was to assess the association between pathogenic and likely pathogenic (P/LP), VUS, and benign and likely benign (B/LB) genetic test results and cancer-related surgical and screening management. Systematic searches of Medline, Embase, EBSCO CINAHL Plus, and PsycINFO were conducted from 1946 to August 26, 2020. Eligible studies included individuals with cancer genetic test result and surgical or screening management outcomes. We reviewed 885 abstracts and 22 studies that reported relevant surgical and screening outcomes were included. Meta-analysis revealed significantly higher surgical rates among individuals with P/LP than among those with VUS for therapeutic mastectomy with contralateral prophylactic mastectomy (OR = 7.35, 95% CI, 4.14-13.64), prophylactic mastectomy (OR = 3.05, 95% CI, 1.5-6.19), and oophorectomy (OR = 6.46, 95% CI, 3.64-11.44). There were no significant differences in therapeutic mastectomy, or breast conservation or lumpectomy rates between individuals with P/LP and VUS, or in any outcomes between patients with VUS and B/LB. Studies evaluating screening outcomes were limited, and results were conflicting. Comprehensive analysis do not indicate that a significant number of individuals with VUS results undergo inappropriate clinical management.

Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.

Epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs). However, the diagnostic and prognostic significance of EpCAM in lung cancer remains largely undetermined. In the present study, we systematically summarized and elucidated the correlation between EpCAM overexpression and lung cancer through a meta-analysis.

Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer.

Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations.

Lung cancer is one of the malignant tumors. Gene mutations associated with cellular immune function and regulating the activation and proliferation of immune cells. Several publications have explored the relationship between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 adenine (A)/guanine (G) polymorphism and susceptibility of lung cancer, but the results remain controversial. Thus, we performed this meta-analysis to derive a more comprehensive estimation of the relationship.

The objective of this study was to conduct a meta-analysis to systematically summarize and investigate the association of miRNA-124 rs531564, miRNA-218 rs11134527, miRNA-146a rs2910164, miRNA-196a2 rs11614913, and miRNA-499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi-square-based Q-test combined with the inconsistency index (I2) was used to check the heterogeneity between studies. A total of six case-control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR-146a rs2910164, miR-196a2 rs11614913, miRNA-499 rs3746444, and miR-218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR-124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87, 95% CI: 1.40-5.91, PH = 0.887), dominant model (GC/CC vs. GG: OR = 1.38, 95% CI: 1.07-1.80, PH = 0.409), and recessive model (CC vs. GC/GG: OR = 2.26, 95% CI: 1.58-3.23, PH = 0.979). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large-scale and well-designed studies are needed to validate our result.

Uveal melanoma (UM) is a malignant tumor that arises in the melanocytes of the uveal tract. It is the most frequent eye cancer, and despite new therapeutic approaches, prognosis is still poor, with up to 50% of patients developing metastasis with no efficient treatment options available. In contrast to cutaneous melanoma, UM is considered an "immune-cold" tumor due to the low mutational burden and the unique immunosuppressive microenvironment. To gain insight into the role of the UM microenvironment in regard to prognosis and metastatic progression, we have performed a pool analysis characterizing the UM microenvironment by using a bioinformatic approach. A variety of scores based on gene expression measuring stromal infiltration were calculated and used to assess association with prognosis. As a result, the highest immune and stromal scores were associated with poor prognosis. Specifically, stromal cells (fibroblasts and endothelial cells), T cells CD8+, natural killer (NK) cells, and macrophages M1 and M2 infiltration were associated with poor prognosis. Contrary to other tumors, lymphocytic infiltration is related to poor prognosis. Only B cells were associated with more favorable prognosis. UM samples scoring high in both angiogenesis (Angio) and antigen presentation (AP) pathways showed a poor prognosis suggesting an additive role of both functions. Almost all these tumors exhibited a chromosome 3 monosomy. Finally, an enrichment analysis showed that tumors classified as high Angio-high AP also activated metabolic pathways such as glycolysis or PI3K-AKT-MTOR. In summary, our pool analysis identified a cluster of samples with angiogenic and inflammatory phenotypes exhibiting poor prognosis and metabolic activation. Our analysis showed robust results replicated in a pool analysis merging different datasets from different analytic platforms.

Methotrexate (MTX), an important chemotherapeutic agent, is often accompanied with mucositis. The occurrence and severity are unpredictable and show large interindividual variability. In this study, we review and meta-analyze previously studied genetic variants in relation to MTX-induced mucositis. We conducted a systematic search in Medline and Embase. We included genetic association studies of MTX-induced mucositis in cancer patients. A meta-analysis was conducted for single nucleotide polymorphisms (SNPs) for which at least two studies found a statistically significant association. A total of 34 SNPs were associated with mucositis in at least one study of the 57 included studies. Two of the seven SNPs included in our meta-analysis were statistically significantly associated with mucositis: MTHFR c.677C > T (recessive, grade ≥3 vs grade 0-2, OR 2.53, 95 %CI [1.48-4.32], False Discovery Rate[FDR]-corrected p-value 0.011) and MTRR c.66A > G (overdominant, grade ≥1 vs grade 0, OR 2.08, 95 %CI [1.16-3.73], FDR-corrected p-value 0.042).

Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment.

Circular RNA PVT1 (circPVT1) is significantly upregulated in various human cancers and is related to poor clinical outcome of cancer patients. However, the prognostic and clinicopathological value of circPVT1 in diverse human cancers remains controversial and inconclusive.