Feng Gao

Background: The diagnostic and prognostic value of HEPACAM family member 2 (HEPACAM2) gene in patients with colon adenocarcinoma (COAD) is rarely reported. Therefore, the purpose of this study is to explore the diagnostic and prognostic value of HEPACAM2 gene in patients with COAD.Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value analysis from different databases. Secondly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. Finally, utilizing joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes.Results: Differential analyses of multiple databases showed that the HEPACAM2 expression level in COAD tumor tissue was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a higher diagnostic value in COAD. The RT-qPCR verification results of COAD tissue in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissue was significantly higher than that of adjacent normal tissues (PHEPACAM2 gene had a poorer prognosis of overall survival (OS) in patients with COAD when compared with those patients with high expression of HEPACAM2 gene ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better prognosis of overall COAD OS.Conclusion: The results of this study suggested that the HEPACAM2 may be an independent diagnostic and prognostic biomarker for COAD.

Colorectal cancer, especially colon adenocarcinoma (COAD), is associated with significant morbidity and mortality worldwide. Long noncoding RNA (lncRNA) has been implicated in tumorigenesis. The aim of the present study was to elucidate the potential diagnostic and prognostic values of lncRNA FRGCA in COAD. The data of 438 COAD patients were retrieved for analysis. Diagnostic significance was evaluated using tumor and nontumor tissues. Prognostic significance was evaluated using a Cox proportional regression model. Stratified analysis was performed to identify associations between clinical factors and lncRNA FRGCA expression. A nomogram was constructed using the clinical factors and lncRNA FRGCA for survival prediction. Enrichment analysis identified gene ontologies and metabolic pathways of mRNAs with high Pearson correlation coefficients with lncRNA FRGCA. lncRNA FRGCA was highly expressed in tumor tissues of COAD and demonstrated diagnostic value (area under curve = 0.763, P < .0001). Prognostic significance analysis indicated that lncRNA FRGCA had prognostic value in COAD [adjusted P < .001, hazard ratio (HR) = 0.444, 95% confidence interval (95% CI) = 0.288–0.685] and high expression of lncRNA FRGCA indicated better survival in COAD. A nomogram was evaluated for prediction of survival at 1, 3, and 5 years. Enrichment analysis revealed many mRNAs involved in the structural constituents of the mitochondrial inner membrane and translational termination, protein binding, translation, ribosome, oxidative phosphorylation, and metabolic pathways, especially the nucleoplasm. Differentially expressed in tumor vs nontumor tissues, lncRNA FRGCA had both diagnostic and prognostic implications in COAD, which may be associated with ribosome metabolism, oxidative phosphorylation, and nucleoplasm-related metabolic pathways.

Background: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD). Methods: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes. Results: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P< 0.001, area under curve (AUC) 95%CI:=0.818 (0.773– 0.862) and ALOX12; P< 0.001, AUC 95%CI=0.774 (0.682– 0.807). Besides, the verification study indicated that ALOX12 had a diagnostic value in COAD. Finally, our multivariate survival analysis and comprehensive prognosis of ALOX genes in COAD suggested that the ALOXE3 and ALOX12 were associated with COAD overall survival: ALOXE3; P=0.025, HR 95%CI=1.765 (1.074– 2.901), ALOX12; P=0.046, HR 95%CI=1.680 (1.009– 2.796), and the low expression of ALOXE3 and ALOX12 had a favorable prognosis of COAD (all P< 0.05); on the contrary, the high regulation of them increased the risk of death. Conclusion: In our study, we observed that the mRNA expressions of ALOX genes were associated with the diagnosis and prognosis of COAD. The results of the diagnostic analysis suggested that ALOX12 might have a diagnosis value in COAD. Besides, our comprehensive prognosis analysis indicated that ALOXE3 combined ALOX12 might serve as potential prognosis biomarkers for COAD.

Purpose: The geriatric nutritional risk index (GNRI) has been reported as a useful tool for predicting the prognosis of many diseases; however, there is currently little research on the relationship between GNRI and outcomes in elderly colorectal cancer (CRC) patients. This study aimed to explore the value of GNRI in evaluating postoperative complication risk and long-term prognosis in elderly CRC patients. Patients and Methods: The medical records of 230 CRC patients aged≥65 years who underwent surgery between January 2012 and December 2014 were retrospectively analyzed. Patients were divided into abnormal and normal GNRI groups by modified binary classification. Logistic regression analysis was used to evaluate the correlation between GNRI and complication risk. The Kaplan–Meier method with log-rank test was used to construct survival curves. The Cox proportional hazard model was used for univariate, multivariate and subgroup survival analyses to assess the relationship between GNRI and long-term prognosis. Results: Multivariate logistic regression analysis showed that GNRI (p = 0.009, HR 2.280, 95% CI: 1.224–4.247) was an independent risk factor for postoperative complications in elderly CRC patients. Kaplan–Meier survival curves revealed that the abnormal GNRI group had significantly lower disease-free survival (DFS; p = 0.005) and overall survival (OS; p=0.007) than the normal GNRI group had, especially in TNM I stage. In multivariate survival analysis, GNRI was an independent prognostic factor for DFS (p = 0.003, HR 1.842, 95% CI: 1.229–2.760) and OS (p = 0.003, HR 1.852, 95% CI: 1.231–2.787). Conclusion: GNRI is a simple and effective tool for predicting the risk of postoperative complications and the long-term prognosis of postoperative elderly CRC patients and can provide a scientific basis for early nutrition interventions in elderly CRC patients.

WNT family genes have participated in the progression and development of many cancers, however, the association between colon adenocarcinoma (COAD) and WNTs have been rarely reported. This study investigated the significance of WNT genes expression in COAD from the standpoint of diagnosis and prognosis. The RNA‐sequencing dataset of COAD was downloaded from The Cancer Genome Atlas and University of California, Santa Cruz Xena browser. The biology functions of WNT genes were investigated by biological analysis. Biological analysis of WNT family genes indicated that WNT genes were noticeably enriched in the complex process of WNT signaling pathway. The Pearson correlation analysis suggested WNT1 and WNT9B had a strong correlation. And receiver operating characteristic curves suggested that most of the genes could serve as a significant diagnostic makers in COAD (P < .05), especially WNT2 and WNT7B had high diagnostic values that the area under curve were 0.997 (95% confidence interval [0.994‐1.000]) and 0.961 (95%CI [0.939‐0.983]), respectively. And our multivariate survival analysis suggested the downregulated of WNT10B (P < .05) showed a favor prognosis in COAD overall survival. And the risk score model predicted that the upregulated expression of WNT10B might increase the risk of death. The very study we had conducted suggested that WNT genes had a certain connection with the diagnosis and prognosis of COAD. The messenger RNA expression of WNT2 and WNT7B might become potentially diagnostic biomarkers, and WNT10B might serve as an independent prognosis indicator for COAD.

The diagnostic and prognostic mechanisms of C‑X‑C motif chemokine ligand 3 (CXCL3) in colon cancer (CC) have not yet been reported. Therefore, the objective of the present study was to use cohorts of patients from Guangxi Medical University and the Gene Expression Omnibus (GEO) database to investigate and validate CXCL3 for the diagnosis and prognosis of CC, and to explore its prospective molecular mechanism. Reverse transcription‑quantitative PCR (RT‑qPCR) analysis of 38 paired tumor and non‑tumor tissues, and immunohistochemistry (IHC) of 212 tumor and 46 non‑tumor tissues was conducted to explore the expression of CXCL3 and its diagnostic and prognostic significance in the Guangxi Medical University CC cohort. A GEO dataset, GSE40967, was used to validate the prognostic significance of CXCL3. Gene set enrichment analysis (GSEA) was also conducted to explore the potential molecular mechanisms underlying the effects of CXCL3 in CC. The RT‑qPCR results indicated that CXCL3 expression was significantly higher in cancer tissues compared with adjacent normal tissues, suggesting that it may have high diagnostic value for CC. Multivariate Cox analysis based on the IHC results suggested that there was no appreciable association between CXCL3 positivity and the overall survival (OS) time of CC. However, a stratified analysis revealed that high expression of CXCL3 was associated with considerably increased mortality in the subgroup of CC patients with tumor size <5 cm (adjusted P=0.042, adjusted HR=2.298, 95% CI=1.030‑5.126) and with tumor thrombus (adjusted P=0.019, adjusted HR=5.096, 95% CI=1.306‑19.886). In the GSE40967 dataset, high expression of CXCL3 was closely associated with poor OS in CC (adjusted P=0.049, adjusted HR=1.416, 95% CI=1.002‑2.003). Furthermore, GSEA indicated that the high expression of CXCL3 was closely associated with DNA repair, cell cycle process, cell apoptosis process and the P53 regulation pathway. In summary, these result suggest that CXCL3 might serve as a novel biomarker in the diagnosis and prognosis of CC.

Purpose: This study aimed to assess the prognostic value of the postoperative serum carcinoembryonic antigen (CEA) levels/preoperative serum CEA levels ratio (CEA ratio) in colorectal cancer (CRC) patients with high preoperative serum CEA levels and to identify the optimal prognostic cutoff value. Patients and methods: The medical records of 187 CRC patients in a single center who underwent surgery between September 2012 and September 2014 were retrospectively reviewed. CEA ratio was defined as the ratio between the postoperative serum CEA and preoperative serum CEA. The optimal cutoff values for the CEA ratio were determined by time-dependent receiver operating characteristic (ROC) curve analyses. The Chi-square test or Fisher’s exact probability test were used to test the correlation between CEA ratio and clinicopathological characteristics. Univariate, multivariate, and subgroup Cox proportional hazards analysis were used to identify independent prognostic factors. Kaplan–Meier method was used for establishing survival curves. Results: The median follow-up time was 62 months (range 3–88 months). The optimal CEA ratio cutoff value closely related to disease-free survival was 0.295. In the Chi-square test, the CEA ratio was associated with pN stage (p=0.003) and postoperative CEA (pp=0.003, HR 2.300 [95% CI: 1.326–3.988]) and cancer-special survival (p=0.003, HR 2.525 [95% CI: 1.381–4.614]). The CEA ratio reflected the prognosis of CRC patients more accurately than postoperative CEA levels alone, and the CEA ratio of 0.295 was more likely to reflect the prognosis than other cutoff values. Conclusion: The CEA ratio is a simple and useful tool for further forecasting the prognosis of CRC patients with high preoperative CEA levels and may help develop strategies for the postoperative treatment of CRC patients.

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin‑mediated signaling pathway, and co‑expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980‑0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577‑0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.

Although interleukin (IL)-9 has been extensively studied in inflammation and autoimmune diseases, the expression level of IL-9 in colon cancer and its clinical significance are less well established. In total, 15 healthy donors (HDs) and 60 patients who had been diagnosed with colon cancer that had undergone a surgical resection were enrolled in the study. The plasma levels of IL-9 in the HDs and cancer patients were detected by the liquid chip technique, while the expression levels of IL-9 in the colon cancer tissues and normal tissues were analyzed using immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, the difference in the expression levels of IL-9 between the patients classified as tumor-node-metastasis stage I–II and stage III–IV was compared. The results demonstrated that the plasma levels of IL-9 in the patients with colon cancer were significantly lower when compared with the HDs (1.29 vs. 2.53 pg/ml, P<0.05). Furthermore, according to the IHC and RT-qPCR results, low expression levels of IL-9 were observed in the colon cancer tissues when compared with the normal tissues (P<0.05). With regard to the plasma and tumor tissue samples, patients diagnosed with stage III–IV colon cancer expressed lower levels of IL-9 compared with the stage I–II patients (P<0.05). In conclusion, low expression levels of IL-9 were observed in the tissue and plasma samples collected from the colon cancer patients, and the decreased expression of IL-9 was shown to correlate with colon cancer progression.