OBJECTIVES: To explore the correlation of ELFN1 expression level with prognosis of colorectal cancer and its regulatory role in colorectal cancer cell proliferation and metastasis. METHODS: We analyzed the expression levels of ELFN1 across 33 cancer types using publicly available databases and identified differential genes related to ELFN1 in colorectal cancer. Gene function annotation and enrichment analysis were used to identify the involved signaling pathways. Logistic analysis, Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the correlation between ELFN1 expression and clinicopathological parameters and survival of colorectal cancer patients. qPCR and Western blotting were used to validate the expression levels of ELFN1 in different colorectal cancer cell lines and tissues, and Transwell and EDU experiments were carried out to assess the effect of ELFN1 knockdown on biological behaviors of SW480 cells. RESULTS: ELFN1 was highly expressed in 14 cancers, and its expression was significantly higher in colon cancer tissues than in adjacent tissues. A high expression of ELFN1 mRNA was associated with a poorer overall survival of colorectal cancer patients. Cox regression analysis indicated that ELFN1 expression was an independent prognostic factor for overall survival of the patients. ELFN1 was significantly enriched in tumor metastasis and proliferation and participated in several tumor signaling pathways. The colon cancer cell lines showed significantly higher expression levels of ELFN1 than normal cells, ELFN1 knockdown obviously inhibited proliferation and migration of SW480 cells in vitro. CONCLUSIONS ELFN1 is overexpressed in colorectal cancer and is associated with poor clinical prognosis of the patients. A high ELFN1 expression is associated with malignant phenotypes of colorectal cancer and promotes cancer cell proliferation and metastasis, suggesting its potential as a prognostic biomarker for colorectal cancer.
Humans ; Colorectal Neoplasms/diagnosis* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Biomarkers, Tumor/metabolism* ; Neoplasm Metastasis ; Gene Expression Regulation, Neoplastic ; Nerve Tissue Proteins/metabolism* ; Female ; Male

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.
Female ; Humans ; Middle Aged ; Class I Phosphatidylinositol 3-Kinases/metabolism* ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis* ; DNA Mismatch Repair/genetics* ; Endometrial Neoplasms/pathology* ; Microsatellite Instability ; Mismatch Repair Endonuclease PMS2/genetics* ; Molecular Typing

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Adenocarcinoma ; Biomarkers, Tumor/genetics* ; Colorectal Neoplasms/pathology* ; DNA Mismatch Repair ; DNA-Binding Proteins/genetics* ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/metabolism* ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Tibet ; Young Adult ; Aged, 80 and over

OBJECTIVETo study the expression of NPAS2 in colorectal cancer (CRC) and analyze its relationship with the clinicopathological parameters and prognosis of the patients.

METHODSReal-time q-PCR was used to detect the expression of NPAS2 mRNA in 40 fresh CRC tissues and paired adjacent tissues; immunohistochemistry was used to detect the expression of NPAS2 protein in 120 paraffin-embedded tumor and adjacent tissues. The relationship between NPAS2 expression level and the 5-year survival rate of 78 CRC patients with follow-up data were analyzed with Kaplan-Meier survival analysis.

RESULTSCompared with the adjacent tissues, fresh CRC tissue expressed significantly lower NPAS2 mRNA levels (P<0.01). Among the paraffin-embedded CRC tissues, 19.2% were positive for NPAS2 expression, as compared to a much higher rate of 62.5% in the adjacent tissues (P<0.05). The expression of NPAS2 was correlated with the tumor size, lymph node metastasis and TNM stages (P<0.05) but not with the patients' gender, age, distant tumor metastasis, differentiation, or invasion. Patients with high NPAS2 expression levels had a significantly higher 5-year survival rate than those with low NPAS2 expressions (P=0.0001).

CONCLUSIONNPAS2 is down-regulated in CRC and closely correlated with the malignant biological behavior of the tumor and 5-year survival of the patients, suggesting its value in predicting the prognosis of the CRC patients.

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Down-Regulation ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Nerve Tissue Proteins ; metabolism ; Prognosis ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Survival Rate

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Colorectal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Esophageal Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Gastrointestinal Tract ; metabolism ; pathology ; Gene Expression ; Humans ; Neoadjuvant Therapy ; methods ; Neoplasm Grading ; Neoplasms, Vascular Tissue ; diagnosis ; drug therapy ; mortality ; secondary ; Prognosis ; SOXB1 Transcription Factors ; genetics ; metabolism ; Stomach Neoplasms ; diagnosis ; drug therapy ; mortality ; pathology ; Survival Analysis

OBJECTIVETo explore the expression of NF-E1b in colorectal cancer tissues and its association with various clinicopathological parameters and prognosis of the patients.

METHODSClinicopathological and follow-up data of 168 colorectal cancer patients undergoing radical operation at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from 2005 to 2012 were retrospectively analyzed, including 96 males and 72 females, with mean age of (57.8±11.2) years. The expression of NF-E1b protein was detected in samples of 168 resected colorectal cancer tissues and 45 adjacent non-cancerous tissues by immunohistochemistry. The expression rates of NF-E1b were compared among different clinicopathological features. Moreover, the association between NF-E1b expression and prognosis was analyzed.

RESULTSThe expression of NF-E1b protein located mainly in cytoplasm. Positive rate of NF-E1b expression in adjacent non-cancerous tissues was 17.8% (8/45), which was obviously lower than 67.9%(114/168) of cancer tissues with significant difference (χ(2)=36.376, P=0.000). Clinicopathological parameters analysis suggested that the expression level of NF-E1b in cancer tissues was associated with age (χ(2)=4.862, P=0.030), TNM staging (χ(2)=10.969, P=0.002), lymph node metastasis (χ(2)=7.390, P=0.008) and distal metastasis (χ(2)=17.887, P=0.000). The median follow-up time was 23(1-77) months. The overall 5-year survival of this cohort was 33.3%. Colorectal cancer patients with high levels of NF-E1b expression showed a worse overall survival compared with those with low levels of NF-E1b expression (18.4% vs. 56.6%, P=0.000). Univariate Cox regression analysis showed that tumor location (P=0.034), tumor size (P=0.003), TNM staging (P=0.000), depth of tumor invasion (P=0.009), lymph node metastasis (P=0.000), distant metastasis (P=0.000) and NF-E1b expression level (P=0.001) were associated with the prognosis of colorectal cancer patients. Multivariate Cox regression analysis revealed that tumor diameter >4 cm (HR=2.193,95% CI:1.334 to 3.603, P=0.002), distant metastasis (HR=2.064, 95% CI:1.160 to 3.672, P=0.014) and high NF-E1b expression (HR=1.994,95% CI:1.068 to 3.724, P=0.030) were independent risk factors of predicting poor prognosis of colorectal cancer patients.

CONCLUSIONSNF-E1b expression up-regulates in colorectal cancer tissues. High expression of NF-E1b is associated with poor prognosis of colorectal cancer patients. NF-E1b may serve as a potential target of the treatment for colorectal cancer.

Aged ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Digestive System Surgical Procedures ; Female ; GATA2 Transcription Factor ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Up-Regulation

OBJECTIVETo investigate the expression of IFITM3 in colorectal carcinoma and its clinical significance.

METHODS213 patients with colon ademocarcinoma and 214 patients with colon adenoma treated by surgery in our hospital from March 2008 to June 2010 were included in this study. The levels of IFITM3 in normal colon nucosa, adenoma, and adenocarcinoma tissues were detected by real-time PCR and immunochemistry, and its relationship with metastasis and prognosis in 213 colorectal cancer patients was analyzed.

RESULTSThe IFITM3 mRNA level in metastatic tumor group was 18.37 ± 0.61, significantly higher than that in the normal 4.49 ± 0.69 and non-metastases groups (7.32 ± 0.76; F = 460.380, P < 0.001). The positive rate of IFITM3 protein expression in metastatic tumor group (69.0%) was significantly higher than that in the normal (3.9%), non-metastasies groups (19.0%) and adenoma groups (11.3%). Our clinical analysis confirmed that the IFITM3 expression was associated with peritumoral invasion, hepatic metastases, metastases of para-colonic lymph nodes, mesocolonic lymph nodes and mesenteric root lymph nodes, omental metastasis and AJCC classification (P < 0.05). Furthermore, the survival curve analysis showed that patients with lower IFITM3 level expression had a higher 5-year survival rate (88.8%) than that in the patients with higher expression (40.2%, P < 0.001).

CONCLUSIONSIFITM3 expression has a positive correlation with metastasis and prognosis in patients with colorectal carcinoma.

Adenocarcinoma ; diagnosis ; metabolism ; Adenoma ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Liver Neoplasms ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Neoplasms ; Peritoneal Neoplasms ; Prognosis ; RNA, Messenger ; RNA-Binding Proteins ; genetics ; metabolism ; Real-Time Polymerase Chain Reaction ; Survival Analysis ; Survival Rate

OBJECTIVETo analyze the clinical significance of syndecan binding protein (SDCBP) expression in human colorectal carcinoma (CRC) and its value in predicting the postoperative survival of the patients.

METHODSThe follow-up data for 10 years were collected from 109 primary CRC patients with immunohistochemical data of SDCBP expression in the tumor tissues. The relationship between SDCBP expression and the clinical factors was analyzed, and survival analysis was performed using the Kaplan-Meier and Cox regression analysis models.

RESULTSSDCBP expression in CRC was significantly associated with the postoperative survival time (χ(2)=8.336, P=0.004) and lymph node metastasis (P=0.001) of the patients, but not with age, gender, depth of invasion, tissue differentiation or histological type of the tumor. Kaplan-Meier survival curves showed that the patients expression high levels of SDCBP in the CRC tissues had a significantly shorter postoperative mean survival time and a lower 7-year survival rate than those with low SDCBP expressions [52.300∓6.508 vs 86.184∓5.358 months, (38.6∓6.4)% vs (61.5∓6.7)%; χ(2)=10.585, P=0.001]. Multivariate Cox analysis revealed that a high expression of SDCBP (B=0.605, P=0.034) and lymph node metastasis (B=0.677, P=0.013) were the main factors related to death in CRC patients.

CONCLUSIONSDCBP expression level can serve as an indicator for lymph node metastasis, TNM staging, and outcome prediction of CRC.

Biomarkers, Tumor ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Survival Rate ; Syntenins ; metabolism

OBJECTIVETo study the diagnostic value of SATB2, together with CK7 and CK20, in colorectal cancer.

METHODSImmunohistochemical study for SATB2, CK7 and CK20 was carried out in 210 cases of colorectal cancer tissue, 100 cases of non-colorectal cancer tissue, 90 cases of lymph node metastases and 50 cases of normal colorectal mucosa.

RESULTSThe sensitivity and specificity of CK20+/CK7- immunophenotype for diagnosis of colorectal adenocarcinoma were 78.1% and 92.0%, respectively. When triple markers were used, the immunophenotype CK20+/CK7-/SATB2+ had a sensitivity of 57.1% and a specificity of 98.0%. When combining the immunophenotype of SATB2+/CK7- or CK20+/CK7-, the sensitivity was 85.7% and specificity was 90.0%.

CONCLUSIONSA panel of immunohistochemical markers SATB2, CK7 and CK20 could increase the specificity for diagnosis of colorectal adenocarcinoma significantly. SATB2 is considered as a useful adjunct in this respect.

Adenocarcinoma ; diagnosis ; metabolism ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Immunophenotyping ; Keratin-20 ; metabolism ; Keratin-7 ; metabolism ; Lymphatic Metastasis ; Matrix Attachment Region Binding Proteins ; metabolism ; Sensitivity and Specificity ; Transcription Factors ; metabolism