miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma.

Accumulating evidence has indicated that microRNAs (miRNAs) play an important role in the occurrence and progression of ovarian cancer (OC). However, the function of miRNAs implicated in OC remains unclear. This study investigated the potential role of miR-211 in OC. Gene Expression Omnibus database analysis indicated that miR-211 expression was significantly down-regulated in OC tissues compared with normal specimens. In addition, miR-211 overexpression apparently inhibited proliferation, migration, xenograft growth, and induced apoptosis in HEY-T30 and SKOV3 cells. Moreover, PHF19, a component of the polycomb group of proteins, was found to be a direct target of miR-211 based on the luciferase reporter assay and Western blot analysis. Consistently, survival analysis indicated that high PHF19 expression was associated with shorter survival time in patients with OC. Importantly, silence of PHF19 reduced proliferation, induced cell cycle arrest, promoted apoptosis, suppressed migration, and inhibited xenograft growth in SKOV3 cells. Restoration of PHF19 expression markedly reversed the inhibitory effect of miR-211 on OC. Moreover, our results indicate that the long noncoding RNA MALAT1 could sponge miR-211 as a competing endogenous RNA and potentially up-regulate PHF19 expression, thus facilitating the OC progression. These findings suggest that the MALAT1/miR-211/PHF19 axis may act as a key mediator in OC and provide new insight into the prevention of this disease.-Tao, F., Tian, X., Ruan, S., Shen, M., Zhang, Z. miR-211 sponges lncRNA MALAT1 to suppress tumor growth and progression through inhibiting PHF19 in ovarian carcinoma.

Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5 cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5 cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5 cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5 cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

Expression of Protein 4.1 Family in Breast Cancer: Database Mining for 4.1 Family Members in Malignancies.

BACKGROUND The protein 4.1 family is a family of cytoskeletal proteins that play an important role in maintaining normal cell morphology and cell adhesion, migration, division, and intercellular signaling. The main aim of this study was to explore the prognostic significance of the protein 4.1 family in breast cancer (BC) patients and to provide new biomarkers and therapeutic targets for the diagnosis and treatment of BC. MATERIAL AND METHODS The expression of 4.1 family members in various tumor types was compared to normal controls using the ONCOMINE and GOBO databases. The prognostic significance of the 4.1 family in BC patients was determined by Kaplan-Meier Plotter. RESULTS EPB41L2 (4.1G) was expressed at higher levels in normal tissues compared with BC patients for all 4.1 family members. In survival analysis, 4.1G and EPB41 (4.1R) mRNA high expressions were associated with better survival in BC patients. Moreover, 4.1G high expression was significantly associated with longer overall survival (OS) in luminal A and protracted relapse-free survival (RFS) in luminal B subtype BC patients who received Tamoxifen treatment. In addition, high expression of each 4.1 family member also showed better prognostic value in different molecular subtypes of BC. CONCLUSIONS These results indicate that the protein 4.1 family can be regarded as novel biomarkers and potential therapeutic targets for BC. Further research is needed to explore the detailed biological functions.

VEGF-C in rectal cancer tissues promotes tumor invasion and metastasis.

PURPOSE: To investigate the relationship between the expression of vascular endothelial growth factor-C (VEGF-C) in rectal cancer tissues and clinicopathological factors. METHODS: The molecular expression of VEGF-C in rectal cancer tissue derived from 45 patients and normal colon tissue from 15 subjects was detected using the immunohistochemical streptavidin/biotin/peroxidase complex (SABC) three-step method. The expression of VEGF-C in rectal cancer and its relationship with clinicopathological factors were statistically analyzed via x2 test or Spearman's rank correlation analysis or Wilcoxon rank sum test. RESULTS: The positive expression rate of VEGF-C was 75.55% in rectal cancer tissues and 6.66% in normal tissues (p<0.01). The positive expression of VEGF-C was not related to patient gender, age and tumor diameter, but related to the grade of differentiation, depth of invasion, lymph node metastasis and Dukes stage (p<0.05). Positive intensity had no statistically significant difference with grade of differentiation and depth of invasion (p>0.05), but had statistically significant difference in lymph node metastasis and Dukes stage (p<0.05). CONCLUSIONS: 1) VEGF-C is highly expressed in rectal cancer tissues; 2) The positive expression of VEGF-C is positively correlated with tumor invasion depth, lymph node metastasis and Dukes stage; 3) Detection of VEGF-C expression can be used as a prognostic marker in rectal cancer.

Aqueous extract of Taxus chinensis (Pilger) Rehd inhibits lung carcinoma A549 cells through the epidermal growth factor receptor/mitogen-activated protein kinase pathway in vitro and in vivo.

OBJECTIVE: To explore the anticancer mechanism of aqueous extract of Taxus Chinensis (Pilger) Rehd (AETC). METHODS: The serum pharmacological method was used to avoid interference from administration of the crude medicinal herbs. Eight purebred New Zealand rabbits were used for preparation of serum containing various concentrations of AETC. Forty-eight Balb/c-nu mice were used for in vivo experiments. The effects of serum containing AETC on the proliferation of A549 cells and expression levels of the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway-related proteins in vitro were investigated. Additionally, the effects on the growth of A549 xenografts in nude mice, and expression levels of the EGFR/MAPK pathway-related proteins in the xenografts, were investigated. RESULTS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the serum containing AETC significantly decreased the viability of A549 cells in a dose-dependent manner. Western blot showed that the serum containing various concentrations of AETC strongly reduced the levels of phospho-Jun N-terminal kinase (p-JNK) and phospho-extracellular signal-regulated kinasel/2 (ERK1/2) while it increased the level of p-p38. However, no significant effects on the expression levels of JNK, ERK1/2, and p38 MAPK were found. In addition, an anticancer effect from AETC was observed in vivo in the Balb/c-nu mice bearing A549 xenografts. CONCLUSION: AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.

[Beta-HIVS combined cisplatin inhibited activities of human ovarian cancer cell line SKOV3 in vitro].

OBJECTIVE: To study the effect of beta-hydroxyisovaleryl shikonin (beta-HIVS) combined cisplatin on activities of ovarian cancer cell line SKOV3 in vivo and its possible mechanisms. METHODS: Cells were divided into the blank control group and six beta-HIVS groups (2 - 30 micromol/L). Effect of beta-HIVS at different concentrations on the activities of ovarian cancer cell line SKOV3 was detected using MTT assay. SKOV3 cells were treated with cisplatin (10, 20, and 40 micromol/L) and beta-HIVS (0.25, 1, and 2.5 micromol/L) combined cisplatin. Effect of beta-HIVS combined cisplatin on the activities of ovarian cancer cell line SKOV3 was determined by MTT assay. The expression of Bcl-2 and Bax after treated by different concentrations of beta-HIVS was detected by Western blot. RESULTS: The activities of SKOV3 were inhibited by different concentrations of beta-HIVS dose-dependently. The 50% inhibition rate (IC50) was 7.37 micromol/L. There was statistical difference in IC50 between each concentration beta-HIVS group and the blank control group (P < 0.05). There was statistical difference in IC50 between the beta-HIVS (1 and 2.5 micromol/L) combined cisplatin groups and the cisplatin group (P < 0.05, P < 0.01). The synergistic effect on beta-HIVS showed dose-dependent manner. Results of Western blot showed beta-HIVS at different concentrations (5, 7.5, and 10 micromol/L) could obviously up-regulate the expression level of Bax protein and inhibit the expression level of Bcl-2 protein, showing statistical difference when compared with the control group (P < 0.01). CONCLUSIONS; HIVS could obviously inhibit in vitro growth of SKOV3 in a dose-dependent manner. With the range of concentration, beta-HIVS showed synergetic effect with cisplatin. Besides, along with increasing beta-HIVS concentrations, the synergetic effect was more significant. The synergetic effect might accelerate the apoptosis of SKOV3 through up-regulating Bax expression and inhibiting Bcl-2 expression.

[Surgical resection versus radiofrequency ablation for primary hepatocellular carcinoma of 3-5 cm in diameter: a meta-analysis].

OBJECTIVE: To compare the therapeutic effects of surgical hepatic resection (HR) and radiofrequency ablation (RFA) in treatment of primary hepatocellular carcinoma of 3-5 cm in diameter. METHODS: The databases PubMed, CBMdisc, CNKI, WanFang Data and VIP databases were searched for controlled clinical trials on evaluating the efficacy between RFA and HR in treatment of primary hepatocellular carcinoma of 3-5 cm in diameter published from January 1990 to February 2014. Two reviewers independently screened the literature, extracted the data and assessed the methodological quality of the studies included. Then the meta-analysis was performed by using RevMan5.0 software. RESULTS: Eleven controlled clinical trials were included, including one randomized controlled trial and 10 non-randomized controlled trials. A total of 811 patients were involved: 404 patients were treated with RFA as the initial treatment and 407 patients with surgical resection. Meta-analysis showed that for a single lesion with diameter of 3-5 cm of primary hepatocellular carcinoma, the 3-， 5-year disease-free survival rates in HR group was significantly higher than those in RFA group (all P<0.05). There were no significant difference in the 1-， 3-， 5-year overall survival rates and 1-year disease-free survival rate between RFA group and HR group (P>0.05). For 1-2 nodules with diameters of 3-5 cm of primary hepatocellular carcinoma, the 3-， 5-year disease-free survival rates and 5-year overall survival rates in HR group was significantly higher than those in RFA group (all P<0.05). No significant difference in 1-， 3-year overall survival rates and 1-year disease-free survival rate was found between RFA group and HR group (P>0.05). For maximum nodule of 3-5 cm of multiple primary hepatocellular carcinoma, the 5-year overall survival rates in HR group was significantly higher than that in RFA group (all P<0.05). No significant difference in 1-， 5-year overall survival rates was noted between RFA group and HR group (P>0.05). CONCLUSION: For primary hepatocellular carcinoma of 3-5 cm in diameter, HR is better than RFA. For the limitation of quality and quantity of included studies, this conclusion needs to be confirmed by more high quality studies.

[Jiedu sangen decoction intervened carcinoma-associated fibroblasts and inhibited migration and invasion of colon cancer: an experimental research].

OBJECTIVE: To observe the effect of Jiedu Sangen Decoction (JSD, consisting of Polygonum cuspidatum, Geum Japonicum Thumnb, Radix Actinidiae Chinensis) on the migration capability of colon cancer CT-26 cells were observed, and on expressions of carcinoma-associated fibroblasts (CAFs) such as transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinase 9 (MMP-9), and alpha-smooth muscle actin (alpha-SMA). METHODS: The BALB/C mice were subcutaneously inoculated with colon cancer CT-26 cells (1.2 x 10(6)mL) and then randomly divided into 3 groups, i.e., the normal control group, the model group, the JSD treated group. The effects of three different serums on the migration ability of colon cancer CT-26 cells were observed using Transwell. The expression quantities of TGF-beta1 and MMP-9 in the supernatant of CAFs were detected using ELISA. The mRNA expression quantities of TGF-beta1 and alpha-SMA in CAFs were detected by real-time fluorescence quantitative PCR. RESULTS: The number of semi-permeable film cells in the JSD treated group significantly decreased, when compared with the model group, showing statistical significance (P < 0.01). Compared with the model group, the expressions of TGF-beta1 and MMP-9 in the supernatant of CAFs decreased in the JSD treated group at 24 and 48 h, showing statistical difference (P < 0.05, P < 0.01). Compared with the model group, the mRNA expressions of TGF-beta1 and alpha-SMA in the JSD treated group obviously decreased, showing statistical difference (P < 0.01). CONCLUSION: JSD could decrease expressions of TGF-beta1 and MMP-9 in the supernatant of CAFs, lower mRNA expressions of alpha-SMA and TGF-beta1, which might be possible mechanisms for inhibiting the migration and invasion of tumor cells.

Correction: Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFß-Induced EMT in Ovarian Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0168892.].

Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: A systematic review and meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a relatively common malignant tumor with high mortality rates. There are limited treatment options and current therapy regimens often fall short of providing positive outcomes. The development of immune checkpoint inhibitors (ICIs) have provided a vital treatment option although efficacy has varied. Here, we review patient response to current TNBC treatment with and without the addition of ICIs. METHODS: A systematic search of PubMed, Cochrane, and EMBASE library databases was done to search eligible studies published from their inception through April 3, 2022. The primary outcome indicators used were progression-free survival (PFS), overall survival (OS), pathological complete response rate (pCR) and objective remission rate (ORR), while adverse events (AEs) were also analyzed. Publication bias and sensitivity analyses and were performed to evaluate the quality of assessment. RESULTS: Overall, the meta-analysis looked at seven randomized controlled trials (RCTs) that included 4631 patients with TNBC. Results showed an improvement in PFS for patients receiving ICI in addition to chemotherapy (CT) in both the intent-to-treat (ITT) population and PD-L1 positive patients. Increased pCR rates were observed in all patients irrespective of PD-L1 status as well as increased ORR in the ITT which was more notable in PD-L1 positive subjects. While significant improvement in OS was observed only in PD-L1 positive individuals, the use of ICIs plus CT resulted in severe adverse reactions, specifically immune-related. CONCLUSIONS: This study supports the increased efficacy of ICIs in combination with CT compared to CT alone in patients with TNBC, with the most notable benefit observed in PD-L1 positive patients. However, combination therapy increases the risk of adverse reactions which warrants further investigation.

[Corrigendum] Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial­mesenchymal transition via the AKT/GSK­3ß/Snail signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the Nc­control and si­AKT1­control data panels featured in Fig. 4A for the SW480 Transwell assay experiments on p. 2788 appeared to contain overlapping data, such that the data, which were intended to show the results from experiments performed under different experimental conditions, may have been derived from the same original source. Furthermore, in Fig. 5 on p. 2789, there appeared to be some overlapping data comparing the AKT1 western blotting data with the p­AKT1 data, and the same data also appeared in Fig. 4D for the p­AKT1 data presented there. The authors have re­examined their original data, and have realized that these figures were assembled incorrectly; essentially, the si­AKT1­control data panel was selected incorrectly for Fig. 4A, and the authors were able to retrieve the original data for the western blots presented in Fig. 5. The corrected versions of Figs. 4 and 5 are shown on the next page. The authors confirm that these errors did not have any major impact on the conclusions reported in their paper, and are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a Corrigendum. Furthermore, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 2783­2795, 2019; DOI: 10.3892/mmr.2019.10528].

Erratum: Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3ß Signaling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.32873.].

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors.

Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4'-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway.

Drug resistance is a major obstacle in the development of effective colorectal cancer (CRC) therapy. Our study aimed to explore the reversal abilities of Jiedu Sangen decoction (JSD) on the 5-fluorouracil (5-FU) resistance and its underlying molecular mechanisms. Expression changes in HIF-1 of CRC tissues were firstly revealed by bioinformatics analysis. Afterwards, cell viabilities of JSD and 5-FU treatments on 5-FU resistant human colon cancer cells (HCT-8/5-FU) were determined. Expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT)/p-AKT, hypoxia-inducible factor 1 (HIF-1α), as well as glycolysis related proteins such as L-lactate dehydrogenase A (LDHA), Glucose transporter type 1 (Glut1), Hexokinase 2 (HKII), and cysteinyl aspartate specific proteinase (Caspase) family members in HCT-8/5-FU cells, HIF-1α silenced HCT-8/5-FU cells and tumor tissues were detected by western blotting. HIF-1α was found over expressed in CRC tissues according to public available datasets in Oncomine. Growth inhibition rates of HCT-8/5-FU cells were increased along with the increase of JSD concentrations. JSD caused down-regulated HIF-1α, PI3K, AKT/p-AKT, HKII and Glut1, as well as up-regulated Caspase3 and Caspase9 in HCT-8/5-FU cells and tumor tissues. In HIF-1α silenced HCT-8/5-FU cells, synergistic group showed significantly reduced expression levels of PI3K, AKT, p-AKT. Additionally, up-regulated expressions of Caspase6 and Caspase7 were observed. JSD combined with 5-FU also exhibited obvious inhibitory efficiency on tumor growth in vivo. JSD may reverse 5-FU resistance by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway, thereby inhibiting glycolysis and induce apoptosis to enhance anti-tumor activity.

Results from a Meta-analysis of Combination of PD-1/PD-L1 and CTLA-4 Inhibitors in Malignant Cancer Patients: Does PD-L1 Matter?

Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been widely used for clinical treatment in recent years, which has a better survival benefit. However, not all patients can derive clinical benefit from combination immunotherapy. Therefore, it is necessary to explore the biomarkers of combination immunotherapy. Methods: We retrieved articles from electronic databases including PubMed, EMBASE and Cochrane. The statistical analysis was performed using RevMan software. Progression free survival (PFS), overall survival (OS) and objective response rate (ORR) were the outcome indicators. In the unselect population, we compared combination therapy with other treatments. In addition, we also conducted subgroup analysis on PFS, OS and ORR according to PD-L1 status. Results: Seven studies were included in the analysis for a total of 3,515 cases. In the unselected population, we found that combination therapy has longer PFS, OS, and better ORR than other treatments for cancer patients. The longer PFS was showed in PD-L1 ≥ 5% cases (HR = 0.64, 95% CI: 0.56-0.76; p < 0.001) than PD-L1 ≥ 1% cases (HR = 0.72, 95% CI: 0.66-0.79; p < 0.001), while ORR and OS have not related to the status of PD-L1. Conclusion: This study supported the efficacy of combination therapy with immune checkpoint inhibitors (ICIs), and also showed that PFS in patients with malignant tumors is positively correlated with PD-L1 expression. Due to the limited number of trials included, more high-quality clinical randomized controlled trials should be conducted to confirm the review findings.

Association of Survival and Immune-Related Adverse Events With Anti-PD-1/PD-L1 and Anti-CTLA-4 Inhibitors, Alone or Their Combination for the Treatment of Cancer: A Systematic Review and Meta-Analysis of 13 Clinical Trials.

BACKGROUND: Cancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer. METHODS: A search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources. RESULTS: A total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60). CONCLUSIONS: ICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.

Becoming a Faithful Defender: Traditional Chinese Medicine against Coronavirus Disease 2019 (COVID-19).

The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.

Risk of Second Primary Malignancies in Colon Cancer Patients Treated With Colectomy.

Background: Second primary malignancy (SPM) attracts a growing attention. However, the clinical features of colon cancer (CC) survivors with SPMs are not clear and could help guide clinicians to develop a better surveillance strategy. Methods: We reviewed 56,930 CC survivors treated with colectomy from the Surveillance, Epidemiology, and End Results (SEER) database during 1998-2011. Competing risk models and nomograms were conducted for predicting the risk of occurring SPMs. The clinical utility of the models was measured by decision curve analysis (DCA) using net benefit approaches. Results: Five thousand thirteen (17.1%) of male patients developed SPMs and sites of SPMs included prostate (32.2%), lung and bronchus (11.6%), urinary bladder and kidney (10.8%), colon (10.0%), and melanoma of the skin (3.9%), while 3,592 (13.0%) of female patients occurred SPMs and sites of SPMs involved breast (25.8%), lung and bronchus (13.6%), colon (11.6%), uterus (8.2%), urinary bladder, and kidney (5.6%). Survivors with a second carcinoma of lung and bronchus showed the worst prognosis. Older age increased the risk of SPMs in both male (Subdistribution hazard ratio =2.85 [95% confidence interval = 2.53-3.21]) and female (1.80 [1.59-2.04]) survivors, especially for the risk of a second prostate carcinoma in male (5.33 [4.03-7.03]). Compared with white race, black male survivors remained at higher risk to develop the second prostate carcinoma (1.98 [1.74-2.26]). Competing-risk nomograms for CC survivors were established to help clinicians predict the probabilities of overall SPMs and prostate carcinoma. Validation of nomograms showed good discrimination and accuracy, and DCAs revealed the clinical effectiveness. Conclusions: We profiled the clinical characteristics of a large population-based cohort of CC survivors with SPMs. These features may improve future follow-up management, especially for the surveillance of second prostate cancer in men and second breast cancer in women.

Identification of biomarkers in colon cancer based on bioinformatic analysis.

BACKGROUND: Colon cancer is one of the most common cancers in the world. Targeting biomarkers is helpful for the diagnosis and treatment of colon cancer. This study aimed to identify biomarkers in colon cancer, in addition to those that have already been reported, using microarray datasets and bioinformatics analysis. METHODS: We downloaded two mRNA microarray datasets (GSE44076 and GSE47074) for colon cancer from the Gene Expression Omnibus (GEO) database and the most recent colon cancer data (COAD) from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) between colon cancer and adjacent normal tissues were determined based on these three datasets. Additionally, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network analysis. The hub genes in the PPI network were then selected and analysed. RESULTS: We identified 150 DEGs and the GO enrichment analysis revealed that these DEGs were enriched in functions related to accelerating the cell cycle, promoting tumour cell accumulation, promoting cell division, positively regulating cell division, and negatively regulating apoptosis. The KEGG pathway analysis indicated that the DEGs were also involved in the cell cycle pathway. In the PPI network, 34 hub genes were found to be enriched in cell division. Prognostic analysis of the 34 hub genes revealed that eight genes (CCNB1, CHEK1, DEPDC1, ECT2, GINS2, HMMR, KIF14, and KIF18A) were associated with the prognosis of colon cancer. And our qRT-PCR results confirmed that DEPDC1, ECT2, GINS2, HMMR and KIF18A were highly expressed in colon cancer cells. CONCLUSIONS: The genes DEPDC1, ECT2, GINS2, HMMR, and KIF18A could serve as novel diagnostic biomarkers of colon cancer.