Previously, microRNA-449a (miR-449a) has been shown to be involved in various types of cancer. However, its role in colorectal carcinoma remains unknown. The present study found that miR-449a expression was significantly increased in cultured colorectal carcinoma cells and cancer tissues obtained from 24 patients diagnosed with colorectal carcinoma, compared with the normal colorectal cells and the adjacent non-tumor tissues. The miR-449a expression in carcinoma tissues revealed an inverse correlation with the levels of serum carcinoembryonic antigen (CEA; R2=0.88). The increased expression of miR-449a appeared in the patients who exhibited normal serum levels of CEA (<5 ng/ml), but not in those with elevated CEA levels (>5 ng/ml). miR-449a expression increased at an early TNM stage (stage II) and did not change significantly at stages III and IV. These results suggested that miR-449a is involved in the development of colorectal carcinoma and may be a potential prognosis indicator.

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen (CEA), human Telomerase Reverse Transcriptase (hTERT), cytokeratin19 (CK19), and programmed death ligand-1 (PD-L1) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab. The CTC chip effectively enriched cells from lung cancer cell line PC-9. The large cell fraction had a high expression of CEA and hTERT, with the former being significantly associated with the clinical response to nivolumab. The expression of CEA and hTERT in CTCs derived from the blood of a patient with lung cancer were also validated. The evaluation of CEA and possibly hTERT in CTCs collected by the CTC chip may represent a promising predictive blood marker for sensitivity to nivolumab. To the best of our knowledge this is the first report to describe the predictive CTC marker for nivolumab in pre-treatment patients.

Uterine leiomyomas (ULs) are the most common gynecological benign tumors originating from the myometrium. Prevalent mutations in the mediator complex subunit 12 (MED12) gene have been identified in ULs, and functional evidence has revealed that these mutations may promote the development of ULs. However, whether MED12 mutations are associated with certain clinical characteristics in ULs remains largely unknown. In the present study, the potential mutations of MED12 and its paralogous gene, mediator complex subunit 12-like (MED12L), were screened in 362 UL tumors from Han Chinese patients. A total of 158 out of 362 UL tumors (43.6%) were identified as harboring MED12 somatic mutations, and the majority of these mutations were restricted to the 44th residue. MED12 mutations were also observed in 2 out of 145 (1.4%) adjacent control myometrium. Furthermore, the mutation spectrum of MED12 in the concurrent leiomyomas was noticeably different. Correlation analysis of MED12 mutations with the available clinical features indicated that patients with mutated MED12 tended to have smaller cervical diameters. By contrast, no MED12L mutation was identified in the present samples. In summary, the present study demonstrated the presence of prevalent MED12 somatic mutations in UL samples, and the MED12 mutation was associated with smaller cervical diameters. The low mutation frequency of MED12 in adjacent control myometrium indicated that MED12 mutation may be an early event in the pathogenesis of ULs. Furthermore, MED12 mutation status in concurrent tumors from multiple leiomyomas supported several prior observations that the majority of these tumors arose independently.

Proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that acts as a transcription factor in several types of tissue. PPAR-γ ligands are known to inhibit numerous cancer cell processes, including pancreatic cancer cell proliferation through terminal differentiation. Previous studies concerning the inhibitory effect of PPAR-γ ligands derived from thiazolidinediones (TZDs) on the metastatic potential of cancer cells have been reported. The present study aimed to investigate whether pioglitazone, a prescription TZD class drug and a ligand of PPAR-γ, inhibits the proliferation and metastasis of pancreatic cancer cells. The inhibitory effect of pioglitazone on the proliferation of the Capan-1, Aspc-1, BxPC-3, PANC-1 and MIApaCa-2 pancreatic cancer cell lines was analyzed. Alterations in carcinoembryonic antigen (CEA), interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) mRNA expression levels subsequent to pioglitazone treatment were examined in BxPC-3 cells by quantitative reverse transcription polymerase chain reaction. In addition, whether the oral administration of pioglitazone prevents tumorigenesis and spontaneous BxPC-3 cell lymph node and lung metastases was investigated using a rectal xenograft model. Pioglitazone treatment resulted in the inhibition of proliferation in all five pancreatic cancer cell lines in vitro. Pioglitazone induced CEA mRNA expression, suppressed IL-8 and COX-2 mRNA expression in vitro, and inhibited BxPC-3 xenograft growth. Pioglitazone also reduced BxPC-3 cell lymph node and lung metastasis in the rectal xenograft model. These results suggest that pioglitazone treatment inhibited the proliferation and metastasis of pancreatic cancer cells through the induction of differentiation and the inhibition of angiogenesis-associated protein expression.

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2- early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2-47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.

Although post-operative adjuvant chemotherapy (ACT) is only recommended for patients with stage II colon cancer who are at a high risk of recurrence, the definition of high risk remains unclear. The present study aimed to identify the risk factors for recurrence, which may also be indicators for adjuvant therapy, using a retrospective analysis of clinicopathological data obtained from stage II colon cancer patients who had undergone a curative resection. The present study also investigated the effects of ACT in patients who displayed the risk factors for recurrence. Univariate and multivariate analyses of the data collected from 377 stage II colon cancer patients, treated at Kurume University Hospital (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and compare the risk factors for recurrence between the 163 patients who had undergone adjuvant therapy and the 214 patients who had not undergone adjuvant therapy. The risk factors for recurrence in patients who had not undergone adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided no benefit to patients who presented with neither risk factor, but significantly decreased the recurrence rate in patients presenting with one or both risk factors. Based on these findings, serum CEA levels of twice the cut-off value and pre-operative bowel obstruction were proposed as indicators in the assessment for adjuvant chemotherapy following a curative resection for stage II colon cancer. These results warrant further clinical study of ACT in patients with one or both risk factors.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) is the major antigen of the CD66 cluster of granulocyte differentiation antigens. The present study aimed to assess the biological function of CEACAM-1 on the growth of human colorectal cancer (CRC) cells in vitro. Treatment of cultured CRC HCT-8 cells with CEACAM-1-specific siRNA successfully downregulated CEACAM-1 expression by 61% compared with control cells. The effects of CEACAM-1 downregulation on HCT-8 cell proliferation and apoptosis were then assessed via Cell Counting kit-8 assay and flow cytometry, respectively. The results demonstrated that siRNA-induced CEACAM-1 downregulation significantly inhibited proliferation and increased apoptosis, but had no significant effect on cell cycle progression in HCT-8 cells. Together, these results suggest that CEACAM-1 activity is critical to CRC growth, and thus, CEACAM-1 may be a promising therapeutic target for the treatment of CRC.

Cisplatin/pemetrexed chemotherapy has been established as a standard treatment in lung adenocarcinoma. However, the response to the cisplatin/pemetrexed combination varies considerably among patients due to individual variations. Thus, novel biomarkers are required to aid the prediction of the response to the cisplatin/pemetrexed combination. We hypothesized that leptin expression may be a determinant for prognosis in lung adenocarcinoma patients with cisplatin/pemetrexed chemotherapy. Serum from consenting patients with lung adenocarcinoma were obtained for the measurement of leptin and associated tumor biomarkers. Leptin expression was measured by radioimmunoassay. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA15-3, CA125, CA72-4, cytokeratin 19 fragment (CYFRA21-1) and neuron-specific enolase (NSE) expression were determined by electrochemiluminescence immunoassays. Serum squamous cell carcinoma antigen levels were measured using a microparticle enzyme immunoassay. The associations between serum leptin and tumor biomarker expression were evaluated by Spearman's correlation analysis. Serum CEA, CA19-9, CA15-3, CA125, CA72-4, CYFRA21-1 and NSE levels showed no obvious difference among patients. However, a trend towards an improved prognosis was observed in patients with lower serum leptin at diagnosis and an increase during cisplatin/pemetrexed chemotherapy. The results indicated that the serum leptin level has prognostic indications in patients with advanced lung adenocarcinoma during cisplatin/pemetrexed chemotherapy, which indicates that it may be a useful marker for the prognosis of cancer patients undergoing chemotherapy treatment.

MicroRNAs (miRNAs/miRs) in extracellular vesicles (EVs) are potential diagnostic markers. The purpose of the present study was to investigate potential EV miRNA biomarkers for lung adenocarcinoma (LUAD). Potential miRNAs were identified by searching public databases and verified by examining clinical samples. The diagnostic value of EV-associated miR-10b, plasma miR-10b and tumor markers (TMs), including α-fetoprotein (AFP), neuron-specific enolase, carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA211), pro-gastrin-releasing-peptide, carbohydrate antigen (CA)125, CA153, CA199 and CA724, was evaluated via receiver operating characteristic curve analysis. By searching the Gene Expression Omnibus and The Cancer Genome Atlas databases, miR-10b was identified as a potential biomarker. The analysis of clinical samples suggested that EV-associated miR-10b from plasma was significantly differentially expressed between LUAD and control samples. EV-associated miR-10b could function as a diagnostic marker for LUAD, with an AUC of 0.998, which was higher than the AUCs for TMs such as AFP, CEA, CYFRA211, CA125, CA153, CA199, CA724, pro-gastrin-releasing-peptide and neuron-specific enolase. In conclusion, EV-associated miR-10b may be a potential diagnostic biomarker for LUAD that is superior to plasma miR-10b and TMs.

Gastric cancer (GC) is the fourth most common tumor and the second most common cause of cancer-associated mortality worldwide. Current tumor biomarkers for GC, such as serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their limited role as prognostic indicators for GC. Proteasome subunit α7 (PSMA7) is a multifunctional protein, which has been revealed to be involved in the development and progression of various types of malignancy. However, little is known about the role of PSMA7 in GC. In the present study, PSMA7 was identified to be overexpressed at the mRNA and protein levels in GC tissues, compared with in non-tumor tissues, using reverse transcription-quantitative PCR and immunohistochemistry. Furthermore, PSMA7 expression is associated with tumor invasion, lymph node metastasis, distant metastasis, and Tumor-Node-Metastasis stage. Univariate and multivariate Cox regression analysis identified that PSMA7 expression is an independent prognostic factor for poor survival. Kaplan-Meier survival curves revealed that high PSMA7 expression is associated with a poor prognosis in patients with GC. Overall, the results of the present study suggested that PSMA7 may be a promising biomarker for the prognosis of GC, and may represent a new diagnostic marker and molecular therapeutic target for GC.

Heterogeneous ribonucleoprotein AB (hnRNP AB) is a member of the heterogeneous nuclear ribonucleoprotein family, which serves important functions in gene expression and signal transduction. However, the expression and clinicopathological significance of hnRNP AB in colorectal cancer (CRC) remain to be elucidated. To investigate the expression and clinical significance of hnRNP AB in CRC, hnRNP AB expression levels were analysed in two independent cohorts of patients with CRC. The results of reverse transcription-quantitative PCR, immunohistochemistry and western blot analysis demonstrated that hnRNP AB was upregulated in CRC tissues compared with the corresponding adjacent normal tissues. Immunohistochemical analyses indicated that a high expression of hnRNP AB was significantly associated with preoperative carcinoembryonic antigen (CEA; P<0.001) and carbohydrate antigen 19-9 (P=0.014) levels, tumour size (P=0.022) and infiltration (P=0.026), lymph node metastasis (P<0.001) and Tumour-Node-Metastasis stage (P<0.001). Univariate and multivariate Cox survival analyses revealed that hnRNP AB expression and preoperative CEA levels were significant independent factors affecting overall survival in patients with CRC (P<0.05). According to the Kaplan-Meier model, patients with CRC with high hnRNP AB expression exhibited significantly poorer prognosis compared with those with low hnRNP AB expression (P<0.001). In conclusion, the results of the present study demonstrated that hnRNP AB expression may serve an important role in the progression of CRC and that hnRNP AB may be considered a predictor of prognosis for patients with CRC.

The present study investigated the value of combinations of five specific tumor biomarkers for the diagnosis of colorectal cancer (CRC): Neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA125 and CA242. Associations between these markers and clinicopathological characteristics (including the Tumor-Node-Metastasis stage) were also assessed. Serum levels of the 5 markers were compared between 358 patients with CRC and 298 healthy individuals (CRC and control group, respectively). The NSE concentration of the CRC group was significantly higher compared with the control. Furthermore, patients at clinical stage III+IV exhibited significantly higher NSE levels compared with those at stage I+II. The serum NSE level of N+ patients was significantly higher compared with the N- group, and the NSE level of M1 patients was significantly compared with the M0 group. NSE level was also significantly associated with tumor stage, lymph node metastasis, distant metastasis and hematochezia. The area under the receiver operating characteristic curve (AUC) for NSE in CRC was 0.766, which was significantly higher than that of the other four markers, which ranged from 0.560-0.682. The AUC of NSE, CEA, CA19-9, CA125, CA242 combined was significantly higher compared with any of the markers individually (range, 0.796-0.858). Therefore, serum NSE may be a good clinical tool for the auxiliary diagnosis of colorectal cancer. Besides, the combination of NSE, CEA, CA19-9, CA125 and CA242 was significantly more sensitive compared with NSE alone. Thus, the combined detection of the 5 tumor markers may be more useful for the diagnosis of CRC.

The present study determined the levels of plasma biomarkers in patients with gastric carcinoma (GC) and investigated their clinical significance and diagnostic value. Between April 2014 and December 2018, 90 patients with GC, 90 patients with precancerous lesions (Pre) and 45 healthy controls (NC) were recruited from the Affiliated Liutie Central Hospital of Guangxi Medical University. Five markers were measured: microRNA-650 (miRNA-650; using reverse transcription-quantitative polymerase chain reaction), and carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA211 and CA50 using electrochemiluminescence. Circulating markers were all upregulated in patients with GC (P<0.05), and CA211 and CA50 were significantly increased in patients with Pre. The miRNA-650 and CA211 had an area under the curve (AUC) of 0.700 (moderate) and 0.866 (high), respectively, in the diagnosis of GC. Differentiation of GC from Pre yielded an AUC of 0.665 (low) and 0.708 (moderate), respectively. The combination model of miRNA-650 and CA211 showed an appropriate value of AUC (0.887) to discriminate the GC patients from the healthy subjects with a sensitivity and specificity of 82.5 and 97.7%. Additionally, differentiating GC from Pre yielded an AUC of 0.767 with a sensitivity of 57.1% and a specificity of 95%, respectively. In terms of clinicopathological features, the expression of miRNA-650 and CA211 in plasma was not associated with the patients' age, sex, Tumor-Node-Metastasis stage, or histological type. In conclusion, plasma miRNA-650 and CA211 is a promising and powerful non-invasive marker for the detection of GC.

The current study clarified the accuracy of a circulating tumor cell (CTC) detection system to diagnose colorectal cancer using blood samples. The system uses the 'polymeric CTC-chip,' (CTC-chip), which is a microfluidic device that is used for CTC isolation. CTCs are considered sensitive diagnostic biomarkers. However, their concentration in the peripheral blood is low and requires highly sensitive and specific capturing techniques. The capture efficiency of the polymeric CTC-chip was first assessed using cell suspensions of the colorectal cancer cell line HCT-116, which was reported as 90.9% in a phosphate-buffered saline suspension and 65.0% in the blood. The CTC-chip was then used to detect CTCs in blood samples obtained from 13 patients with stage II-IV colorectal cancer. On average, the CTCs/ml was lower in patients with stages II and III colorectal cancer (3.3±2.3) than in those with stage IV (7.0±6.2). In patients with stages II-IV, 92% had ≥1 CTC per ml, which was significantly higher than the positive rate (15%) detected using the carbohydrate antigen 19-9 test (CA19-9). Furthermore, CTCs were detected in all patients with stage II and III colorectal cancer, including a number of patients with negative results for the carcinoembryonic antigen (CEA) and CA19-9 tests. With the polymeric CTC-chip detection system, CTCs can be effective cancer markers, particularly for patients with stage II and III colorectal cancer who often exhibit negative conventional serum marker test results. The CTC-chip system may also facilitate the detection of cancer progression based on CTC concentration.

C4b-binding protein α-chain (C4BPA) was previously identified as a novel serum biomarker for pancreatic ductal adenocarcinoma (PDAC). To apply this biomarker for clinical diagnosis, a lectin ELISA was established to measure serum fucosylated (Fuc)-C4BPA levels in 45 patients with PDAC, 20 patients with chronic pancreatitis (CP) and 50 healthy volunteers (HVs) in one training and three validation sets. The lecithin ELISA developed in the current study exhibited satisfactory within-run (2.6-6.7%) and between-day (1.8-3.6%) coefficient of variations. Serum Fuc-C4BPA levels in patients with PDAC (0.54±0.27 AU/ml) was significantly higher than that in HVs (0.21±0.06 AU/ml; P<0.0001) and patients with CP (0.25±0.03 AU/ml; P<0.0001). Additionally, serum Fuc-C4BPA levels in preoperative patients were significantly decreased compared with postoperative patient sera (P<0.0003). The receiver operating characteristic (ROC) curve analyses revealed that the area under the curve (AUC) of Fuc-C4BPA (0.985) was higher than that of carbohydrate antigen (CA)19-9 (0.843), carcinoembryonic antigen (0.548) and total C4BPA (0.875) (P<0.001). To analyze the clinical significance of Fuc-C4BPA, the ability of Fuc-C4BPA to predict lymph node metastasis was compared with that of CA19-9. The AUC of serum Fuc-C4BPA levels (0.703) was significantly higher than that of serum CA19-9 levels (0.500) in patients with PDAC (P<0.001). The current study established a novel lectin ELISA for measuring serum Fuc-C4BPA levels. Thus, Fuc-C4BPA has potential clinical applications owing to its high diagnostic value in PDAC.

Gut microbes influence tumor development and progression in the intestines and may provide a novel paradigm for the treatment of colorectal cancer (CRC). Gut dysbiosis may be associated with the development and progression of CRC. Identifying the interactions between the colonic tract and gut microbiota may provide novel information relevant to CRC prevention. The present study examined the effects of butyrate-producing Butyricicoccus pullicaecorum (B. pullicaecorum) on mice with 1,2-dimethylhydrazine (DMH)-induced CRC and the microbial metabolite of B. pullicaecorum on CRC cells. Immunohistochemical staining of the mouse colon tissues and reverse transcription PCR of CRC cells were used to determine the protein and mRNA expression levels of the short-chain fatty acid (SCFA) transporter solute carrier family 5 member 8 (SLC5A8) and G-protein-coupled receptor 43 (GPR43). In CRC-bearing mice fed B. pullicaecorum, DMH-induced CRC regressed, body weight increased and serum carcinoembryonic antigen levels decreased. Notably, SLC5A8 and GPR43 were diffusely and moderately to strongly expressed in the neoplastic epithelial cells and underlying muscularis propria in the colons of the mice. In conclusion, administration of B. pullicaecorum or its metabolites improved the clinical outcome of CRC by activating the SCFA transporter and/or receptor. These results indicated that B. pullicaecorum was a probiotic with anti-CRC potential.

The current study aimed to develop multiple diagnosis models for colorectal cancer (CRC) based on data from The Cancer Genome Atlas database and analysis with artificial neural networks in order to enhance CRC diagnosis methods. A genetic algorithm and mean impact value were used to select genes to be used as numerical encoded parameters to reflect cancer metastasis or aggression. Back propagation and learning vector quantization neural networks were used to build four diagnosis models: Cancer/Normal, M0/M1, carcinoembryonic antigen (CEA) <5/≥5 and Clinical stage I-II/III-IV. The performance of each model was evaluated by predictive accuracy (ACC), the area under the receiver operating characteristic curve (AUC) and a 10-fold cross-validation test. The ACC and AUC of the Cancer/Normal, M0/M1, CEA and Clinical stage models were 100%, 1.000; 87.14%, 0.670; 100%, 1.000; and 100%, 1.000, respectively. The 10-fold cross-validation test of the ACC values and sensitivity for each test were 93.75-99.39%, 1.0000; 80.58-88.24%, 0.9286-1.0000; 67.21-92.31%, 0.7091-1.0000; and 59.13-68.85%, 0.6017-0.6585, respectively. The diagnosis models developed in the current study combined gene expression profiling data and artificial intelligence algorithms to create tools for improved diagnosis of CRC.

Alterations of mitochondrial DNA (mtDNA) have been identified in several types of solid tumor. However, to the best of our knowledge, the clinical significance of plasma mtDNA content in lung cancer remains unknown. Thus, the current study explored the diagnostic and prognostic value of plasma mtDNA quantification in patients with lung cancer. Plasma mtDNA copy numbers of patients with lung cancer (n=128) and healthy individuals (n=107) were quantified by quantitative polymerase chain reaction. Plasma mtDNA copy numbers in patients and healthy controls were 0.89×104 and 1.37×104 copies/µl, respectively (P<0.0001). Furthermore, lower plasma mtDNA content was associated with tumor size, lymph node metastases, distant metastases and serum carcinoembryonic antigen levels (P<0.05), but was not associated with pathological type, age, sex or main driver gene mutation status (P>0.05). Plasma mtDNA facilitated the detection of lung cancer at a threshold of 1.19×104 copies/µl with a sensitivity of 71.1% and specificity of 70.1%, as determined by receiver operating characteristic curve analysis. Advanced stage (III and IV) patients with a lower mtDNA copy number (cutoff: 1.02×104 copies/µl) tended to exhibit poorer prognosis (P<0.05). These results indicated that plasma mtDNA content is a promising and complementary candidate with tissue mtDNA for diagnosis and prognostic prediction for lung cancer.

In our previous studies, a functionally unknown gene, family with sequence similarity 172, member A (FAM172A), was identified. High levels of FAM172A suppressed the cell cycle process, arresting HepG2 cells in G1/S and inhibiting cell proliferation. The present study aimed to confirm the expression levels of FAM172A and nucleotide-binding protein 1 (NUBP1) in colorectal cancer (CRC) tissues and normal colorectal tissues. The impact of FAM172A and NUBP1 on the prognosis of patients with CRC was also analyzed. Immunohistochemical staining for FAM172A and NUBP1 was performed on 180 cancerous tissues and 60 normal paraffin-embedded tissues from patients with CRC. In total, 85 and 83% of 180 patients revealed positive expression of FAM172A and NUBP1, respectively. FAM172A expression level was associated with Tumor-Node-Metastasis (TNM) staging (P<0.001), the levels of serum carcinoembryonic antigen (CEA; P=0.023) and carbohydrate antigen 19-9 (CA19-9; P=0.016), lymph node involvement (P=0.004), tissue type (P=0.016), Dukes' staging (P<0.001) and NUBP1 (P=0.026). Furthermore, the expression level of NUBP1 was also markedly associated with the levels of serum CEA (P=0.006) and CA19-9 (P=0.001), TNM staging (P<0.001), lymph node involvement (P=0.005), histological typing (P=0.024) and Dukes' stage (P<0.001). Results of the univariate analysis demonstrated that there was a negative correlation between the expression level of FAM172A and overall survival (OS) and relapse-free survival (RFS) (P=0.013 and P=0.012, respectively), and there was also a negative correlation between NUBP1 expression level and OS and RFS (P<0.001 and P<0.001, respectively). With regards to OS and RFS, multivariate analysis revealed that expression levels of FAM172A and NUBP1 and tumor stage may be independent prognostic factors Thus, the present study suggested that FAM172A and NUBP1 may be prognostic makers for CRC.

The molecular mechanisms underlying the development and progression of colorectal cancer (CRC) have not been clarified. The purpose of the present study was to identify key genes that may serve as novel therapeutic targets or prognostic predictors in patients with CRC using bioinformatics analysis. Four gene expression datasets were downloaded from the Gene Expression Omnibus database, which revealed 19 upregulated and 34 downregulated differentially expressed genes (DEGs). The downregulated DEGs were significantly enriched in eight pathways according to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. A protein-protein interaction network was constructed with 52 DEGs and 458 edges. Ten key genes were identified according to the degree value, betweenness centrality and closeness centrality. Survival analysis revealed that low expression of four of the ten genes, carcinoembryonic antigen related cell adhesion molecule 7 (CEACAM7), solute carrier family 4 member 4 (SLC4A4), glucagon (GCG) and chloride channel accessory 1 (CLCA1) genes, were associated with unfavorable prognosis in CRC. Furthermore, gene set enrichment analysis revealed that two pathways were significantly enriched in the CEACAM7 low-expression group. Thus, CEACAM7, SLC4A4, GCG and CLCA1 may be prognostic markers or therapeutic targets of CRC. Low CEACAM7 expression may be associated with the activation of glycosaminoglycan biosynthesis-chondroitin sulfate and extracellular matrix receptor interaction pathways and may affect the prognosis of CRC.