Search

ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo-blood group (ABH) antigens and ABO gene in ovarian tumor tissues.To assess the impact of genotype-derived ABO blood types on the risk of EOC, we conducted a case-control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues.We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03-1.36, p = 0.019). Increased frequency of aberrant expression of histo-blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p 0.001). ABO gene expression was down-regulated in ovarian tumor tissues compared with paired adjacent normal tissues (p = 0.027). In addition, ABO gene expression was positively correlated with NFYB (r = 0.38, p 0.001) and inversely correlated with DNA methylation level of four CpG sites on ABO gene (cg11879188, r = - 0.3, p = 0.002; cg22535403, r = - 0.30, p = 0.002; cg13506600, r = - 0.22, p = 0.025; cg07241568, r = - 0.21, p = 0.049) in ovarian tumor tissues.We identified blood group A was associated with increased EOC risk in Chinese women and provided the clues of the possible molecular mechanisms of blood group A related to ovarian cancer risk.

Introduction Cervical cancer has high mortality, high recurrence and poor prognosis. Although prognostic biomarkers such as clinicopathological features have been proposed, their accuracy and precision are far from satisfactory. Therefore, novel biomarkers are urgently needed for disease surveillance, prognosis prediction and treatment selection. Materials Differentially expressed genes (DEGs) between cervical cancer and normal tissues from three microarray datasets extracted from the Gene Expression Omnibus platform were identified and screened. Based on these DEGs, a six‐gene prognostic signature was constructed using cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas. Next, the molecular functions and related pathways of the six genes were investigated through gene set enrichment analysis and co‐expression analysis. Additionally, immunophenoscore analysis and the QuartataWeb Server were employed to explore the therapeutic value of the six‐gene signature. Results We discovered 178 overlapping DEGs in three microarray datasets and established a six‐gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) prognostic signature with stable and excellent performance in predicting overall survival in different subgroups. Intriguingly, the six‐gene signature was closely associated with the immune response and tumour immune microenvironment. The six‐gene signature might be used for predicting response to immune checkpoint inhibitors (ICIs) and the six genes may serve as new drug targets for cervical cancer. Conclusion Our study established a novel six‐gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) signature that was closely associated with the immune response and tumour immune microenvironment. The six‐gene signature was indicative of aggressive features of cervical cancer and therefore might serve as a promising biomarker for predicting not only overall survival but also ICI treatment effectiveness. Moreover, three genes (UPP1, ISG20 and GLTP) within the six‐gene signature have the potential to become novel drug targets., Our study established a novel six‐gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) signature that was closely associated with the immune response and the tumour immune microenvironment. The six‐gene signature was indicative of aggressive features of cervical cancer and therefore might serve as a promising biomarker for predicting not only overall survival but also immune checkpoint inhibitor treatment effectiveness. Moreover, three genes (UPP1, ISG20 and GLTP) within the six‐gene signature have the potential to become novel drug targets.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important driver gene of non-small cell lung cancer (NSCLC). Despite a rapid progress achieved in the targeted therapy, chemotherapy remains the standard treatment option for patients with KRAS-mutant NSCLC. This study aimed to assess real-world data of Chinese patients with KRAS-mutant NSCLC undergoing chemotherapy and/or immunotherapy.KRAS mutational status was analyzed using next-generation sequencing of 150,327 NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I). Treatment data were collected and analyzed retrospectively from 4348 NSCLC patients who were admitted to the Peking University Cancer Hospital and Institute between January 2009 and October 2020 (Cohort II).In Cohort I, 18,224 patients were detected with KRAS mutations (12.1%) of whom G12C (29.6%) was the most frequent subtype, followed by G12D (18.1%) and G12V (17.5%). In case of concomitant mutations, TP53 had the highest incidence of 33.6%, followed by EGFR (11.6%), STK11 (10.4%), KEAP1(6.2%), and CDKN2A (6.0%). Cohort II included 497 patients (11.4%) with KRAS mutations. In the first-line chemotherapeutic analysis of Cohort II, patients benefited more from the pemetrexed/platinum (PP) regimen than the gemcitabine/platinum (GP) or taxanes/platinum (TP) regimen (median progression-free survival [PFS], 6.4 vs. 4.9 vs. 5.6 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.48-0.88, p = 0.033 and HR = 0.69, 95% CI 0.47-1.00, p = 0.05, respectively), with no significant difference when combined with bevacizumab. Regarding patients who received immune checkpoint inhibitors (ICIs), the objective response rate was 26% for a median PFS of 9.6 months (95% CI 6.16-13.03). Patients who received ICIs combined with chemotherapy had a significantly longer survival than monotherapy (median PFS, 13.9 vs. 5.2 months, HR = 0.59, 95% CI 0.35-0.99, p = 0.049).KRAS is an important driver gene in NSCLC, compromising 12.1% in this study, and G12C was noted as the most common subtype. Patients with KRAS-mutant NSCLC could benefit from pemetrexed-based chemotherapy and ICIs.

This study aimed to explore the roles of ERCC1/XPF gene polymorphisms in the occurrence of breast cancer in the Uygur and Han ethnic groups in Xinjiang, China. Single nucleotide polymorphisms (SNPs) were detected by TaqMan real‐time PCR. The rs11615 G>A and rs2276466 C>G variant frequencies were higher in Uygur patients with breast cancer than in Han patients, while the frequency of rs2298881 C>A was higher in Han patients. We found that rs2298881 C>A (CA vs. CC: OR = 0.35, 95% CI = 0.20‐0.60; AA vs. CC: OR = 0.13, 95% CI = 0.04‐0.34; CA + AA vs. CC: OR = 0.33, 95% CI = 0.18‐0.51; AA vs. CA + CC: OR = 0.24, 95% CI = 0.08‐0.62; CA vs. AA + CC: OR = 0.49, 95% CI = 0.29‐0.82) was associated with a reduced breast cancer risk and rs3212986 C>A (AA vs. CC: OR = 4.80, 95% CI = 1.79‐15.29,; CA+AA vs. CC: OR = 1.71, 95% CI = 1.06‐2.77; AA vs. CA+CC: OR = 4.12, 95% CI =1.58‐12.89) and rs11615 G > A (AA vs. GG: OR = 3.49, 95% CI =1.54‐8.55; GA + AA vs. GG: OR = 1.98, 95% CI = 1.21‐3.27; AA vs. GA+GG: OR = 2.87, 95% CI = 1.30‐6.85) were associated with an elevated breast cancer risk among Uygur individuals. In addition, Uygur patients with breast cancer with 2‐3 combined risk genotypes of ERCC1 had a higher risk than patients with 0‐1 risk genotypes (OR = 2.91; 95% CI = 1.54‐5.71, p = 0.001). However, we failed to detect a statistically significant association between ERCC1/XPF polymorphisms and breast cancer risk in five genetic models among Han individuals. Our results showed that ERCC1/XPF gene polymorphisms predispose Uygur individuals to breast cancer; this finding should be verified by further large‐scale analyses., Distribution of ERCC1/XPF gene polymorphisms in Han and Uygur women with breast cancer was different. ERCC1/XPF gene polymorphisms predispose Uygur individuals to breast cancer.

Objective To compare survival outcomes of minimally invasive surgery (MIS) and laparotomy in early‐stage cervical cancer (CC) patients. Methods A multicenter retrospective cohort study was conducted with International Federation of Gynecology and Obstetrics (FIGO, 2009) stage IA1 (lymphovascular invasion)‐IIA1 CC patients undergoing MIS or laparotomy at four tertiary hospitals from 2006 to 2017. Propensity score matching and weighting and multivariate Cox regression analyses were performed. Survival was compared in various matched cohorts and subgroups. Results Three thousand two hundred and fifty‐two patients (2439 MIS and 813 laparotomy) were included after matching. (1) The 2‐ and 5‐year recurrence‐free survival (RFS) (2‐year, hazard ratio [HR], 1.81;95% confidence interval [CI], 1.09‐3.0; 5‐year, HR, 2.17; 95% CI, 1.21‐3.89) or overall survival (OS) (2‐year, HR, 1.87; 95% CI, 1.03‐3.40; 5‐year, HR, 2.57; 95% CI, 1.29‐5.10) were significantly worse for MIS in patients with stage I B1, but not the cohort overall (2‐year RFS, HR, 1.04; 95% CI, 0.76‐1.42; 2‐year OS, HR, 0.99; 95% CI, 0.70‐1.41; 5‐year RFS, HR, 1.12; 95% CI, 0.76‐1.65; 5‐year OS, HR, 1.20; 95% CI, 0.79‐1.83) or other stages (2) In a subgroup analysis, MIS exhibited poorer survival in many population subsets, even in patients with less risk factors, such as patients with squamous cell carcinoma, negative for parametrial involvement, with negative surgical margins, negative for lymph node metastasis, and deep stromal invasion, MIS exhibited poorer survival outcomes than laparotomy in many population subsets, even in low‐risk subgroups. Therefore, laparotomy should be the recommended approach for cervical cancer patients.

Glucocorticoids (GC) are the foundation of the chemotherapy regimen in acute lymphoblastic leukemia (ALL). However, resistance to GC is observed more frequently than resistance to other chemotherapy agents in patients with ALL relapse. Moreover, the mechanism underlying the development of GC resistance in ALL has not yet been fully uncovered. In this study, we used bioinformatic analysis methods to integrate the candidate genes and pathways participating in GC resistance in ALL and subsequently verified the bioinformatics findings with in vitro cell experiments. Ninety‐nine significant common differentially expressed genes (DEGs) associated with GC resistance were determined by integrating two gene profile datasets, including GC‐sensitive and ‐resistant samples. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) and REACTOME pathways analysis, the signaling pathways in which DEGs were significantly enriched were clustered. The GC resistance‐related biologically functional interactions were visualized as DEG‐associated Protein–Protein Interaction (PPI) network complexes, with 98 nodes and 127 edges. MYC, a node which displayed the highest connectivity in all edges, was highlighted as the core gene in the PPI network. Increased C‐MYC expression was observed in adriamycin‐resistant BALL‐1/ADR cells, which we demonstrated was also resistant to dexamethasone. These results outlined a panorama in which the solitary and scattered experimental results were integrated and expanded. The potential promising target of the candidate pathways and genes involved in GC resistance of ALL was concomitantly revealed., These results outlined a panorama in which the solitary and scattered experimental results were integrated and extended. The potential promising target of the candidate pathways and genes in GC resistant acute lymphoblastic leukemia was concomitantly revealed.

MicroRNAs (miRNAs) are noncoding single‐stranded RNAs, approximately 20‐24 nucleotides in length, known as powerful posttranscriptional regulators. miRNAs play important regulatory roles in cellular processes by changing messenger RNA expression and are widely involved in human diseases, including tumors. It has been reported in the literature that miRNAs have a precise role in cell proliferation, programmed cell death, differentiation, and expression of coding genes. MicroRNA‐124 (miR‐124) has reduced exparession in various human neoplasms and is believed to be related to the occurrence, development, and prognosis of malignant tumors. In our review, we focus on the specific molecular functions of miR‐124 and the downstream gene targets in major cancers, which provide preclinical evidence for the treatment of human cancer. Although some obstacles exist, miR‐124 is still attracting intensive research focus as a promising and effective anticancer weapon., miRNA‐124 is closely related to the cancer development and progression, and decreased in many cancer types. Increasing miRNA‐124 levels, inhibiting cancer cell proliferation, and affecting clinical outcome. miRNA‐124 has the potential to be a target for cancer treatment.

Background Natural Killer T–Cell Lymphoma (NKTCL) is a subtype of Non‐Hodgkin's Lymphoma, and its morbidity is ranked the first of T‐Cell Lymphoma. Hippo signaling pathway is involved in the pathogenesis of tumors. However, the role of Hippo signaling pathway in the oncogenesis of NKTCL still remains unclear. Methods The expressions of mammalian sterile 20‐like kinase 1 (MST1) and Yes‐associated protein (YAP) were investigated by RT‐PCR and Western blotting. Cell viability was detected by MTT assays. Cell cycle and cell apoptosis were determined by flow cytometry. Cell proliferative capacity was detected by colony formation assay. Nude mice xenograft models were established and the tumor sections were analyzed by immunohistochemistry (IHC) staining. Results The expression of MST1 was significantly down‐regulated in NKTCL tissues (n = 30) and cell lines, while the expression of YAP was significantly up‐regulated, and the phosphorylation of YAP was inhibited. Overexpression of MST1, knockdown of YAP, or verteporfin (VP) treatment could inhibit cell proliferation, and promote cell cycle arrest and apoptosis in NKTCL cells, while knockdown of MST1 and overexpression of YAP promoted cell proliferation. Additionally, Bcl‐2/Bax ratio and downstream effectors of Hippo signaling pathway (c‐myc, survivin, cyclinD1, CTGF, and TEAD) were significantly decreased when MST1 was overexpressed and YAP was knocked down or after VP treatment. Furthermore, our mice model demonstrated that activation of Hippo signal pathway suppressed the tumorigenesis of NKTCL. Conclusion The activation of Hippo signal pathway via overexpressing MST1 or down‐regulating YAP can inhibit the tumorigenesis of NKTCL.

Multidimensional interactions of multiple factors are more important in promoting cancer initiation. Gene‐gene interactions between protein‐coding genes have been paid great attention, while rare studies refer to the interactions between encoding and noncoding genes. Our research group previously found encoding gene PGC polymorphisms could affect the susceptibility to atrophic gastritis (AG) and gastric cancer (GC). Interestingly, several SNPs in long noncoding RNA (lncRNA) genes, just adjacent to PGC, were found to be associated with AG risk and GC prognosis afterward. This study aims to explore the SNP interactions between PGC and its neighbor lncRNAs on the risk of AG and GC. Genotyping for seven PGC SNPs and seven lncRNA SNPs was conducted using Sequenom MassARRAY platform in a total of 2228 northern Chinese subjects, including 536 GC cases, 810 AG cases, and 882 controls. We found 15 pairwise PGC‐lncRNAs SNPs had interactions: Five pairs were associated with AG risk, and ten pairs were associated with GC risk. Moreover, two GC‐related interactions PGC rs6939861 with lnc‐C6orf‐132‐1 rs7749023 and rs7747696 survived the Bonferroni correction (P correction = 0.049 and 0.007, respectively). Several combinations showed obvious epistasis and cumulative effects on disease risk. Some three‐way interactions of SNPs with smoking and drinking could also be observed. Besides, a few interacting SNPs showed correlations with the expression levels of PGC protein and related lncRNAs in serum. Our study would provide research clues for further screening combination biomarkers uniting both protein‐coding and noncoding genes with the potential in prediction of the susceptibility to GC and its precursor.

A dynamic and mutualistic interaction between tumor cells and tumor microenvironment (TME) promotes the progression and metastasis of solid tumors. Cancer immunotherapy is becoming a major treatment paradigm for a variety of cancers. Although immunotherapy, especially the use of immune checkpoint inhibitors, has achieved clinical success, only a minority of patients exhibits durable responses. Clinical studies directed at identifying appropriate biomarkers and immune profiles that can be used to predict immunotherapy responses are presently being conducted. Combining treatment strategies tailored to cancer‐immune interactions are designed to increase the rate of durable clinical response in patients. It is essential to establish a reasonable tumor classification strategy according to TME to improve cancer immunotherapy. In the current review, a modified classification of TME is proposed, and optimization of TME classification is needed through detailed and integrated molecular characterization of large patient cohorts in the future.

Exosomal microRNAs have recently been studied as the potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and Western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR‐39 microRNA mimics. Serum exosomal level of miR‐122, miR‐148a, and miR‐1246 was further analyzed and significantly higher in HCC than LC and normal control (NC) groups (P 0.05). The receiver operating characteristic curve was used to evaluate the diagnostic performance of candidate microRNAs. Area under the curve (AUC) of miR‐148a was 0.891 [95% confidence interval (CI), 0.809–0.947] in discriminating HCC from LC, remarkably higher than alpha‐fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607–0.803). Binary logistic regression was adopted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR‐122, miR‐148a, and AFP increased the AUC to 0.931 (95% CI, 0.857–0.973), which can also be applied for distinguishing early HCC from LC. miR‐122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945–1.000). These data suggest that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.

FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor‐dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small‐hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis. Immunofluorescence was used to detect the formation of γH2AX foci and evaluate the extent of DNA damage. Compared with corresponding adjacent noncancerous cervical tissues, the expression of FUNDC1 in cervical cancer cells was significantly increased. High expression of FUNDC1 and the prognosis of patients with cervical cancer were correlated negatively, which could be used as an independent prognostic factor for overall survival and disease‐free survival. Depletion of FUNDC1 significantly inhibited the proliferation of tumor cells, induced apoptosis, and enhanced cell sensitivity to cisplatin and ionizing radiation (IR). Our data suggested that FUNDC1 can be used as a prognostic biomarker in patients with cervical cancer, and may be a new therapeutic target to improve the antitumor effects of chemoradiotherapy.

Linc00152, located on chromosome 2p11.2, is a long intergenic non‐coding RNA molecule with 828 nucleotides that is highly expressed in many types of human tumor tissues, especially in malignant tumors of the digestive system. Linc00152 promotes the occurrence and development of tumors by increasing tumor cell proliferation, invasion, metastasis, and apoptosis. Additionally, linc00152 contributes to the carcinogenesis of several cancers, including gastric cancer, liver cancer, hepatocellular carcinoma, gallbladder cancer, clear cell renal cell carcinoma, and colorectal cancer, by disturbing various signaling pathways (eg PI3K/AKT, mTOR, IL‐1, and NOTCH 1 signaling pathways). High linc00152 expression levels are associated with chemoresistance as well as poor prognosis and shorter survival. Continual advances made in the relevant research have indicated that linc00152 may be useful as a new tumor molecular biomarker, applicable for tumor diagnosis, targeted therapy, and prognosis assessment. This review summarizes the progress in the research into the relationship between linc00152 and the occurrence and development of malignancies based on molecular functions, regulatory mechanisms, and clinical applications.

Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta‐analysis. PubMed and Embase were searched up to January 2015. Prospective or case–control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed‐effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case‐control studies and 1 pooled analysis of 14 case‐control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03‐1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01‐1.22; I2=31.1% and RR=1.16, 95% CI 1.01‐1.33; I2=19.6% respectively). The dose‐response analysis suggested neither a non‐linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta‐analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose‐response relationship suggests that further studies are needed to better understand the relationship.