Serum cell division cycle 42 in advanced hepatocellular carcinoma patients: Linkage with clinical characteristics and immune checkpoint inhibitor-related treatment outcomes.

OBJECTIVE: Cell division cycle 42 (CDC42) facilitates immune escape and drug resistance towards immunotherapy in several malignancies. This prospective study aimed to explore the predictive value of serum CDC42 for immune checkpoint inhibitor (ICI)-treatment response and survival in advanced hepatocellular carcinoma (HCC) patients. METHODS: Thirty advanced HCC patients scheduled for ICI or ICI-based treatment were enrolled in this prospective study, whose serum CDC42 was determined via enzyme-linked immunosorbent assay before therapy initiation. RESULTS: The median (interquartile range) of serum CDC42 level was 766.5 (605.0-1329.5) pg/mL. Serum CDC42 was related to increased tumor size but decreased programmed death-ligand 1 combined positive score (PD-L1 CPS). With respect to ICI or ICI-based treatment outcomes, elevated serum CDC42 was associated with decreased disease control rate, but did not link with objective response rate. Patients with high serum CDC42 (vs. low, cut by its median level) had shortened progression-free survival (PFS), while overall survival (OS) only disclosed a reduced trend (lacked statistical significance) in patients with high serum CDC42 (vs. low). In detail, the median (95%CI) PFS and OS were 3.0 (0.0-6.0) months and 11.7 (2.7-20.7) months in patients with high serum CDC42, while they were 11.1 (6.6-15.6) months and 19.3 (14.5-24.1) months in patients with low CDC42. After adjusted by multivariate cox regression analysis, high serum CDC42 (vs. low) was independently associated with shortened PFS, but not OS. CONCLUSIONS: Elevated serum CDC42 possesses a potential value in predicting worse ICI or ICI-based treatment outcomes in advanced HCC.

Detection of serum HE4 levels contributes to the diagnosis of lung cancer.

Lung cancer (LC) is the most frequently diagnosed cancer and is the leading cause of cancer-associated death. Serum markers that exhibit high sensitivity and specificity for LC may assist in the diagnosis and prognosis of LC. The banked serum samples from 599 individuals, including 201 healthy controls, 124 patients with benign lung diseases, and 274 LC cases, were used. The serum concentrations of biomarkers were determined by electrochemiluminescence immunoassay and chemiluminescence immunoassay. The results showed that the serum human epididymis secretory protein 4 (HE4) levels in the LC group were significantly higher than in the healthy and benign lung disease groups. The serum levels of HE4, NSE, and CYFRA21-1 were significantly higher in patients with LC compared to those in the benign lung disease group. The area under the area under the curve (AUC) of HE4 for discriminating LC from healthy controls was 0.851 (95% CI, 0.818-0.884) and 0.739 (95% CI, 0.695-0.783), 0.747 (95% CI, 0.704-0.790), 0.626 (95% CI, 0.577-0.676), and 0.700 (95% CI, 0.653-0.747) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 combined with NSE, CYFRA21-1, SCC, and proGRP for cancer diagnosis was 0.896 (95% CI, 0.868-0.923). In early LC, the AUC value of HE4 for discriminating early LC from healthy controls was 0.802 (95% CI, 0.758-0.845), 0.728 (95% CI, 0.679-0.778), 0.699 (95% CI, 0.646-0.752), 0.605 (95% CI, 0.548-0.662), and 0.685 (95% CI, 0.630-0.739) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 with NSE, CYFRA21-1, SCC, and proGRP for early LC was 0.867 (95% CI, 0.831-0.903). Serum HE4 is a promising LC biomarker, particularly for early-stage LC. Measuring serum HE4 levels may improve the diagnostic efficiency of LC.

Value of serum miR-21, HE4 and CA125 in surveillance for postoperative recurrent or metastatic ovarian cancer.

Objectives: To study the value of serum miR21, human epididymal secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the surveillance for postoperative recurrent or metastatic ovarian cancer. Methods: A total of 169 patients diagnosed with ovarian conditions in Luanzhou Hospital of Traditional Chinese Medicine during January 2016 and March 2019 were divided into a benign lesion (BL) group and an ovarian cancer (OC) group by pathological findings and assigned to a good prognosis (GP) group and a poor prognosis (PP) group according to the follow-up results. A real-time fluorescence quantitative PCR (RT-fqPCR) system was utilized to detect the serum level of miR-21; an enzyme-linked immunosorbent assay (ELISA) was conducted to determine the serum level of HE4; electrochemiluminescence (ECL)-based imaging analysis was performed to measure serum CA125. A receiver operating characteristic (ROC) curve was depicted to analyze the predictive value of serum miR-21, HE4, and CA125 for poor postoperative prognosis in patients with ovarian cancer. Results: Compared with the control group, the BL and OC groups had substantially elevated expression of miR-21, HE4, and CA125 in serum, and the serum levels of miR-21, HE4, and CA125 in the OC group were significantly higher than in the BL group. In the OC group, the serum levels of miR-21, HE4, and CA125 were independent of age and pathological patterns and associated with the clinical staging, degree of transformation and lymphatic metastasis of ovarian cancer; after laparoscopic ovarian tumorectomy, the serum levels of miR-21, HE4, and CA125 were markedly reduced in comparison with the preoperative levels. Compared with the GP group, the PP group experienced a dramatic increase in serum miR-21, HE4, and CA125 expression. The ROC curve showed that the detection of miR-21, HE4, and CA125 was a highly sensitive and specific method to predict the poor prognosis in ovarian cancer; a patient with ovarian cancer was at high risk of a poor prognosis when the serum levels of miR-21, HE4, and CA125 exceeded 1.536, 157.004 pmol/L and 175.243 kU/L, respectively, in which case early intervention should be made to prevent recurrent or metastatic ovarian cancer. Conclusion: Elevated expression of miR-21, HE4, and CA125 in serum is closely associated with the disease status of ovarian cancer. Therefore, the simultaneous detection of these tumor markers has some diagnostic value for postoperative recurrence and metastasis of ovarian cancer.

microRNA-10a-5p overexpression suppresses malignancy of colon cancer by regulating human liver cancer fibroblasts.

The crosstalk between tumor and stroma plays a critical role in cancer metastasis. However, the function of miR-10a-5p on liver fibroblasts in the metastatic microenvironment of colon cancer (CC) and the effect of activated fibroblasts on CC cells are still unclear. In our study, miR-10a-5p overexpression inhibited the proliferation, migration, and IL-6/IL-8 level of LX-2 cells and human liver cancer fibroblasts (HLCFs). Moreover, miR-10a-5p had lower expression in HLCFs than in human liver normal fibroblasts (HLNFs). The conditioned medium (CM) from LX-2 cells with miR-10a-5p overexpression or HLNFs could inhibit the invasion, migration, and stemness of CC SW480 cells, whereas HLCFs CM could promote these malignant phenotypes of SW480 cells. The present study illustrates the effect of miR-10a-5p on the liver fibroblasts and the altered liver fibroblasts in the microenvironment on CC cells induced by miR-10a-5p, which may aid the understanding of the mechanisms underlying CC liver metastasis.

MicroRNA-20a contributes to cisplatin-resistance and migration of OVCAR3 ovarian cancer cell line.

MicroRNAs (miRs) have been reported to be associated with the development of numerous types of cancer. However, the function of miRs in human ovarian carcinoma chemoresistance remains largely undefined. In the present study, cell chemotherapy combined with a Cell Counting Kit-8 assay demonstrated that miR-20a performed important roles in ovarian cancer cells chemoresistance. Flow cytometry, cellular proliferation assays and Transwell assays results revealed that the proliferation and migration rates of OVCAR3/DDP cells were increased in comparison with parental cells. Western blot analysis results suggested that epithelial-mesenchymal transition (EMT) activated by miR-20a contributed to OVCAR3/DDP cell migration. The present study highlighted the importance of miR-20a in regulating the chemoresistant properties of OVCAR3 cells and promoting cisplatin-resistant cell migration by activating EMT. The results of present study may therefore provide novel insights into reversing the chemoresistance of ovarian cancer and improving its treatment.

Complement receptor 1 genetic variants contribute to the susceptibility to gastric cancer in chinese population.

As the receptor for C3b/C4b, type 1 complement receptor (CR1/CD35) plays an important role in the regulation of complement activity and is further involved in carcinogenesis. This study aimed to elucidate the association of CR1 genetic variants with the susceptibility to gastric cancer in Chinese population. Based on the NCBI database, totally 13 tag single nucleotide polymorphisms (SNPs) were selected by Haploview program and genotyped using iPlex Gold Genotyping Assay and Sequenom MassArray among 500 gastric cancer cases and 500 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression to evaluate the association of each SNP with gastric cancer. Of all selected Tag SNPs , CR1 rs9429942 T > C was found to confer to the risk of developing gastric cancer. Compared with the carriers with rs9429942 TT genotype, those with CT genotype had 88% decreased risk of developing gastric cancer with OR (95%CI) of 0.12 (0.03-0.50). Generalized multifactor dimensionality reduction (GMDR) analysis revealed a significant three-way interaction among rs75422544 C > A, rs10494885 C > T and rs7525160 G > C in the development of gastric cancer with a maximum testing balance accuracy of 56.07% and a cross-validation consistency of 7/10 (P = 0.011). In conclusion, our findings demonstrated the genetic role of CR1 gene in the development of gastric cancer in Chinese population.

The tag SNP rs10746463 in decay-accelerating factor is associated with the susceptibility to gastric cancer.

BACKGROUND: Complement activation involved in the innate immunity and adaptive immunity and further contributed to the development of tumor growth. This study aimed to investigate the association of genetic variants in complement 3 (C3) and decay-accelerating factor (DAF) genes with the risk of gastric cancer. METHODS: This case-control study included 500 gastric cancer patients and 500 cancer-free controls. Based on the Chinese population data from HapMap database, we used Haploview 4.2 program to select candidate tag SNPs. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression to evaluate the association of each genetic variant with the risk of gastric cancer. RESULTS: Among 12 tag SNPs of C3, no correlation was observed between C3 genetic variants and risk of gastric cancer. For tag SNPS of DAF, logistic regression analysis revealed that the carriers with DAF rs10746463 AA genotype had a significantly increased risk for developing gastric cancer (OR = 1.46, 95% CI = 1.01­2.10) when compared with GG genotype, but those carrying with rs10746463 AG genotype didn't (OR = 1.31, 95% CI = 0.98-1.75). When stratified by smoking status, we found that the risk of gastric cancer was associated with rs10746463 GA or AA genotype carriers among smoker with OR (95% CI) of 1.64 (1.06-2.54), but not among non-smoker (OR = 1.37, 95% CI = 0.97-1.94). CONCLUSION: DAF rs10746463 polymorphism effects on the risk of developing gastric cancer in Chinese population.

CYP1A2 rs762551 polymorphism contributes to cancer susceptibility: a meta-analysis from 19 case-control studies.

BACKGROUND: Genetic polymorphism (rs762551A>C) in gene encoding cytochrome P450 1A2 (CYP1A2) has been shown to influence the inducibility of CYP1A2 expression and thus might be associated with risk of several types of human cancer. However, the results of previous studies on the associations of this polymorphism with risk of cancer are not all consistent. To clarify the potential contribution of CYP1A2 rs762551 to cancer risk, we performed a meta-analysis of the published case-control studies. METHODS: We used PubMed, Embase, OVID, ScienceDirect, and Chinese National Knowledge Infrastructure databases to identify the related publications for this meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random effect model to evaluate the association of rs762551 with cancer risk. A χ(2)-based Q-test was used to examine the heterogeneity assumption and the funnel plot and Egger's test were used to examine the potential publication bias. The leave-one-out sensitivity analysis was conducted to determine whether our assumptions or decisions have a major effect on the results of the review. RESULTS: Our analysis of 19 eligible case-control studies showed a significant association between rs762551C variant with risk of cancer in the genetic model of CC versus AA (OR = 1.30, 95% CI = 1.02-1.64) and the dominant model (OR = 1.19, 95% CI = 1.04-1.36). In subgroup analysis based on ethnicity, the rs762551CC genotype was associated with increased cancer risk (OR = 1.29, 95% CI = 1.27-1.63 in co-dominate model and OR = 1.17, 95% CI = 1.02-1.34 in dominant model in Caucasians, but not in Asians and the mixed population. CONCLUSION: These results suggested that CYP1A2 rs762551 polymorphism is likely to be associated with susceptibility to cancer in Caucasians.