Prognostic Factor In Colorectal Cancer Research Articles

Clinical implication of tissue carcinoembryonic antigen expression in association with serum carcinoembryonic antigen in colorectal cancer

This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection.

CD51 Intracellular Domain Promotes Cancer Cell Neurotropism through Interacting with Transcription Factor NR4A3 in Colorectal Cancer.

The abundant nervous system in intestine provides the basis for perineural invasion (PNI) of colorectal cancer (CRC). PNI is defined as the invasion of the nerves by cancer cells. Although PNI is already known to be an independent prognostic factor in CRC, the molecular mechanism underlying PNI remains obscure. In this study, we first demonstrated that CD51 could promote the neurotropism of tumor cells through cleavage with γ-secretase to generate an intracellular domain (ICD). Mechanistically, ICD of CD51 could bind to the transcription factor NR4A3, and act as a coactivator to promote the expression of downstream effectors, such as NTRK1, NTRK3, and SEMA3E. Pharmacological inhibition of γ-secretase impedes PNI mediated by CD51 in CRC both in vitro and in vivo and may become a potential therapeutic target for PNI in CRC.

Molecular prognostic factors in colorectal cancer: 5-year follow-up.

Colorectal cancer (CRC) is a frequently diagnosed and lethal disease. The risk of developing CRC is determined by environmental and genetic factors. Surgical treatment is the main curative modality for patients with CRC up to stage III. In recent years, a special place has been given to biological agents used as targeted therapy following the genetic analysis of the tumor: Bevacizumab (Avastin), Cetuximab (Erbitux), Ziv-aflibercept (Zaltrap). We present a study based on 46 colorectal tumor resection specimens from patients operated for CRC in the Surgery Departments of the Emergency County Clinical Hospital of Craiova, Romania. Histopathological examination and immunohistochemistry staining of tissue sections were performed to determine the degree of aggressiveness. Using the Kaplan-Meier test, we calculated the correlation coefficient between survival time and immunohistochemical prognostic factors. The patients were followed for 60 months postoperatively.

Prognostic Value of Immunoscore in Colorectal Carcinomas.

Aims. Immunoscore, based on the evaluation of CD3+ and CD8+ densities in the center of the tumor and its invasive margin, is currently considered as a potential prognostic factor, particularly in colorectal carcinomas. In the current study, we aimed to assess the prognostic value of immunoscore in colorectal cancer stage I to IV, through a survival study. Methods and Results. It was a descriptive and retrospective study involving 104 cases of colorectal cancer. Data were collected over 3 years (2014-2016). An immunohistochemical study (anti-CD3, anti-CD8) by the tissue microarray technique was carried out in the areas of "hot spot" in the tumor center and invasive margin. A percentage was assigned to each marker and within each region. Then, the density was classified as "low" or "high," according to a cutoff fixed at the median of percentages. immunoscore was calculated by the method described by Galon et al. The prognostic value of the immunoscore was assessed through a survival study. The mean age of patients was 61.6 years. immunoscore was low in 60.6% (n = 63). Our study had shown that low immunoscore significantly deteriorates survival and a high immunoscore enhances survival significantly (P < .001). We found a correlation between immunoscore and T stage (P = .026). A multivariate showed that the predictive factors for survival were immunoscore (P = .001) and age (P = .035). Conclusions. Our study highlights the potential role of immunoscore as a prognostic factor in colorectal cancer. Its reproducibility and reliability allow its introduction into daily practice for better therapeutic management.

Immunological and prognostic significance of tumour necrosis in colorectal cancer

BackgroundColorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC.MethodsThree independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined.ResultsHigher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68–6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour.ConclusionsOur results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.

A novel inflammation-related signature for predicting prognosis and characterizing the tumor microenvironment in colorectal cancer.

Inflammation is a critical component of tumor progression, and it modifies the tumor microenvironment by various mechanisms. Here, we explore the effect of the inflammatory response on the tumor microenvironment in colorectal cancer (CRC). A prognostic signature consisting of inflammation-related genes (IRGs) was constructed and verified based on the inflammatory response by bioinformatics analysis. IRG risk model was identified as an independent prognostic factor in CRC, and was related to biological processes of extracellular matrix, cell adhesion and angiogenesis. The IRG risk score predicted the clinical benefit of ipilimumab. Weighted correlation network analysis identified TIMP1 as the hub gene of the inflammatory response in the IRG risk model. Coculture experiments with macrophages and CRC cells revealed that TIMP1 promoted macrophage migration, inhibited the expression of M1 markers (CD11C and CD80), and promoted the expression of M2 markers (ARG1 and CD163). TIMP1 promoted the expression of ICAM1 and CCL2 by activating the ERK1/2 signaling pathway to promote macrophage migration and M2-like polarization. These IRGs in the risk model regulated stromal and immune components in the tumor microenvironment and could serve as potential therapeutic targets in CRC. TIMP1 promoted macrophage migration and meditated macrophage M2 polarization by activating ERK1/2/CLAM1 and CCL2.

Colorectal cancer lymph node metastasis prediction with weakly supervised transformer-based multi-instance learning

Lymph node metastasis examined by the resected lymph nodes is considered one of the most important prognostic factors for colorectal cancer (CRC). However, it requires careful and comprehensive inspection by expert pathologists. To relieve the pathologists’ burden and speed up the diagnostic process, in this paper, we develop a deep learning system with the binary positive/negative labels of the lymph nodes to solve the CRC lymph node classification task. The multi-instance learning (MIL) framework is adopted in our method to handle the whole slide images (WSIs) of gigapixels in size at once and get rid of the labor-intensive and time-consuming detailed annotations. First, a transformer-based MIL model, DT-DSMIL, is proposed in this paper based on the deformable transformer backbone and the dual-stream MIL (DSMIL) framework. The local-level image features are extracted and aggregated with the deformable transformer, and the global-level image features are obtained with the DSMIL aggregator. The final classification decision is made based on both the local and the global-level features. After the effectiveness of our proposed DT-DSMIL model is demonstrated by comparing its performance with its predecessors, a diagnostic system is developed to detect, crop, and finally identify the single lymph nodes within the slides based on the DT-DSMIL and the Faster R-CNN model. The developed diagnostic model is trained and tested on a clinically collected CRC lymph node metastasis dataset composed of 843 slides (864 metastasis lymph nodes and 1415 non-metastatic lymph nodes), achieving the accuracy of 95.3% and the area under the receiver operating characteristic curve (AUC) of 0.9762 (95% confidence interval [CI]: 0.9607–0.9891) for the single lymph node classification. As for the lymph nodes with micro-metastasis and macro-metastasis, our diagnostic system achieves the AUC of 0.9816 (95% CI: 0.9659–0.9935) and 0.9902 (95% CI: 0.9787–0.9983), respectively. Moreover, the system shows reliable diagnostic region localizing performance: the model can always identify the most likely metastases, no matter the model’s predictions or manual labels, showing great potential in avoiding false negatives and discovering incorrectly labeled slides in actual clinical use.Graphical

Tumor deposits are associated with a higher risk of peritoneal disease in non-metastatic colorectal cancer patients.

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high-risk (HR) features in CRC patients. A retrospective cohort-study of stage I-III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4-stage. A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7-1.9) years in the TD group compared to 1.4 (0.8-2.1) years in the HR group (p = 0.31). In non-metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HRcounterparts. Alternative strategies for surveillance and treatment should be considered.

Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells.

Rab GTPase 3C (RAB3C) is a peripheral membrane protein that is involved in membrane trafficking (vesicle formation) and cell movement. Recently, researchers have noted the exocytosis of RAB proteins, and their dysregulation is correlated with drug resistance and the altered tumor microenvironment in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in the carcinogenicity of colorectal cancer (CRC) remain unknown. Researchers have used various in silico datasets to evaluate the expression profiles of RAB family members. We confirmed that RAB3C plays a key role in CRC progression. Its overexpression promotes exocytosis and is related to the resistance to several chemotherapeutic drugs. We established a proteomic dataset based on RAB3C, and found that dystrophin is one of the proteins that is upregulated with the overexpression of RAB3C. According to our results, RAB3C-induced dystrophin expression promotes vesicle formation and packaging. A connectivity map predicted that the cannabinoid receptor 2 (CB2) agonists reverse RAB3C-associated drug resistance, and that these agonists have synergistic effects when combined with standard chemotherapy regimens. Moreover, we found high dystrophin expression levels in CRC patients with poor survival outcomes. A combination of the dystrophin and RAB3C expression profiles can serve as an independent prognostic factor in CRC and is associated with several clinicopathological parameters. In addition, the RAB3C-dystrophin axis is positively correlated with the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) genetic alterations in CRC patients. These findings can be used to provide novel combined therapeutic options for the treatment of CRC.

Clinicopathologic and prognostic factors for colorectal cancer in children and adolescents: a population-based study.

Colorectal cancer (CRC) is rarely found in children and adolescents. The purpose of this study was to retrospectively conduct a population-based cohort of pediatric patients with CRC. All pediatric patients with CRC diagnosed between 1975 and 2018 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. The demographics and clinical variables of the patients were summarized, and treatment outcomes and prognostic factors were examined. The study was presented in accordance with the STROBE reporting checklist. A total of 284 CRC patients were identified. At 3- and 5-year follow-up, the overall survival rates were 63.1% and 52.6%, respectively. Patients with local disease had a significantly improved overall survival (OS) than patients with distant disease. At 3- and 5-year follow-up, the overall survival rates of adenocarcinoma (nos) and adenocarcinoma (polyp) were similar and significantly better than those of patients with mucinous adenocarcinoma and signet ring cell carcinoma (P < 0.001). In terms of treatment, patients who underwent surgery outlived non-surgery patients (3-year OS, 70.4% versus 26.6%, P < 0.001). Multivariate analysis revealed that SEER stage and histologic type were important independent predictors of outcomes. Children and adolescents with CRC are likely to be in an advanced stage, have a worse histologic subtype, and have a poorly differentiated grade. Although surgical resection considerably increases survival for the majority of patients, pediatric patients with CRC have a poor prognosis. Considerable efforts are required to improve their survival outcomes.

Tumor necrosis factor-α-inducible protein 8-like protein 3 (TIPE3): a novel prognostic factor in colorectal cancer

BackgroundTo explore the correlation of tumor necrosis factor-α-induced protein 8-like protein 3 (TIPE3) expressions in colorectal cancer (CRC) with tumor-immune infiltration and patient prognosis.MethodsFormalin-fixed paraffin-embedded tumor samples from CRC patients (n = 110) were used in this study. Immunohistochemistry staining of TIPE3 and three prognostic immune biomarkers (CD8, CD20, and CD66b) was conducted in the tumor tissues and adjacent normal tissues. A Cox regression analysis of univariate and multivariate variables was performed to assess the correlation between TIPE3 and patient prognosis.ResultWe found that TIPE3 was mainly expressed in the cytoplasm, with a small amount in the nucleus. The expression of TIPE3 in tumor tissues is significantly higher than in adjacent normal tissues, and it is significantly correlated with the survival rate of patients in tumor tissues (p = 0.0038) and adjacent normal tissues (p<0.0001). Patients with a high TIPE3 expression had a lower survival rate, while patients with a low TIPE3 expression had a higher survival rate. Univariate regression analysis showed that the TIPE3 expression in tumor tissues (p = 0.007), the TIPE3 expression in adjacent normal tissues (p<0.001), the number of CD8+ T cells in tumor tissues (p = 0.020), the number of CD20+ B cells in tumor tissues (p = 0.023), the number of CD20+ B cells in adjacent normal tissues (p = 0.023), the number of CD66b+ neutrophils in tumor tissues (p = 0.005), the number of CD66b+ neutrophils in adjacent normal tissues (p<0.001), lymphatic metastasis (p = 0.010), TNM stage (p = 0.013), and tumor grade (p = 0.027) were significantly correlated with overall survival (OS). These prognostic factors were then subjected to multivariate regression analysis, and the results showed that the expression of TIPE3, the number of CD8+ T cells, and the number of CD66b+ neutrophils were prognostic factors affecting the OS rate of CRC patients.ConclusionWe found that the TIPE3 protein is upregulated in CRC cancer tissues and is correlated with survival rate.

Prognostic significance of the cachexia index in patients with stage I-III colorectal cancer who underwent laparoscopic surgery.

The prognostic significance of the cachexia index, a novel biomarker of cancer cachexia, remains unclear in colorectal cancer; we, therefore, evaluated this relationship. This retrospective cohort study included 306 patients with stage I-III colorectal cancer who underwent R0 resection between April 2010 and March 2020. The cachexia index was calculated as (skeletal muscle index [cm2/m2] × serum albumin level [g/dL])/neutrophil-to-lymphocyte ratio. The overall and disease-free survival rates were analyzed using a Cox proportional hazards model. A low cachexia index was found in 94 patients. This group had significantly lower disease-free survival and overall survival than the high-cachexia index group (5-year survival, 86.3% vs. 63.1%, p < 0.01; 87.9% vs. 67.2%, p < 0.01). Multivariate analyses showed that T3 or T4 (hazard ratio [HR]: 2.56; 95% confidence interval CI 1.04-6.25, p = 0.039), stage III (HR: 3.77; 95% CI 1.79-7.93, p < 0.01), and a low cachexia index (HR: 2.27; 95% CI 1.31-3.90, p = 0.003) were significant independent predictors of the disease-free survival. CA19-9 ≥ 37.0ng/mL (HR: 2.68; 95% CI: 1.37-5.24, p = 0.004), stage III (HR: 2.57; 95% CI 1.34-4.92, p = 0.004), and a low cachexia index (HR: 2.35; 95% CI 1.31-4.21, p = 0.004) were significant independent predictors of the overall survival. A low cachexia index might be a long-term prognostic factor of colorectal cancer.

Tumour Cell Seeding to Lymph Nodes from In Situ Colorectal Cancer.

Lymph node (LN) metastasis is an important prognostic factor in colorectal cancer (CRC). We aimed to demonstrate the presence of lymphatic vessels (LV) in the mucosa of in-situ (pTis) CRC, and of detectable tumour burden in regional LNs. This is an observational retrospective study of 39 surgically resected in situ CRCs. The number of LVs was evaluated in both pTis and normal mucosa using D2-40 immunostains. All LNs were assessed with both H&E and the One Step Nucleic Acid Amplification (OSNA) assay, and the results were correlated with clinicopathological features. D2-40 immunohistochemisty revealed LVs in the lamina propria of all pTis CRC (100%), being absent in normal mucosa. A median of 16 LNs were freshly dissected per patient, and all cases were pN0 with H&E. Molecular LN analysis with OSNA revealed the presence of low amounts of tumour burden in 11/39 (28%) cases (range 400 to 4270 CK19 mRNA copies/µL), which had no clinical consequences. This study demonstrates the presence of LVs in the lamina propria in 100% of pTis CRC, as well as the presence of low amounts of tumour burden in regional LNs, only detected by molecular methods. Given the prognostic value of LN tumour burden, its molecular quantification may help a patient's clinical management.

Survival Analysis and Prognostic Factors for Metastatic Colorectal Cancer Patients Treated with Chemotherapy

Background: Currently, there are limited data on prognostic factors in metastatic colorectal cancer (mCRC) patients treated with chemotherapy. Prognostic factors in colorectal cancer remain varied in each situation when considering their use in different contexts. Objective: To analyze the independent prognostic factors of mCRC in patients receiving chemotherapy. Materials and Methods: Data from 156 mCRC patients completely treated by first-line chemotherapy were collected between 2013 and 2018. A retrospective observational cohort study was conducted to evaluate the survival analysis and prognostic factors. A univariate and multivariate Cox’s proportional-hazards model were used to explore and identify the independent prognostic factors for overall survival. An analysis of the restricted mean survival time (RMST) method was used to estimate the event-free time from zero to 24 months. Results: Median overall survival was 18.3 months (96% CI 15.31 to 20.95). The multivariate Cox’s proportional-hazards model revealed two rognostic factors for decreased survival, poor Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 2 (HR 2.05, 95% CI 1.08 to 3.86; p=0.027) and hypoalbuminemia lower than 3.5 g/dL (HR 3.47, 95% CI 2.10 to 5.75, p&lt;0.001). Analysis of the RMST method was used to estimate the event-free time from zero to 24 months in the group receiving first-line oxaliplatin-based chemotherapy, secondline oxaliplatin-based chemotherapy, and second-line irinotecan-based chemotherapy. It was found that only the group receiving second-line oxaliplatin-based chemotherapy had significantly longer survival time than the comparison groups, with an adjusted mean of survival time of 21.12 months (different mean 5.99, 95% CI 3.99 to 8.00, p&lt;0.001). Conclusion: Poor ECOG performance status greater than or equal to 2, and hypoalbuminemia lower than 3.5 g/dL can be used as prognostic factors in mCRC patients receiving chemotherapy. Keywords: Survival; Prognostic factors; Metastatic colorectal cancer; Chemotherapy

Usefulness of Elastica van Gieson staining and the number of samples prepared for venous invasion of colorectal cancer (pT2–pT4)

AimsAlthough venous invasion is an important prognostic factor for colorectal cancer, it may be significantly underestimated in actual daily diagnosis. In this study, hematoxylin–eosin (HE)- and Elastica van Gieson (EVG)-stained specimens of colorectal cancer (pT2–pT4) were obtained, and the influence of the number of specimens and the number of EVG-stained specimens on the prognosis were examined. Methods and resultsThe presence or absence of venous invasion in 100 colon cancer (pT2–pT4) specimens obtained after surgical resection was observed. Assessments were made by comparing the sections, of either the specimens of the deepest part of the tumor or the whole tumor, stained with only HE, as well as a combination of HE and EVG stains. There was a relative low agreement rate between the assessments made using whole-tumor EVG-stained sections and those employing other methods. With respect to relapse-free survival, no significant difference was observed in the prognosis of cases evaluated using HE-stained samples alone relative to the presence of venous invasion. However, for evaluations made using EVG staining, a significant difference was seen even for deepest-section assessments, and this trend was even stronger when whole-tumor sections were evaluated (EVG [deepest]: P = 0.0128, EVG [whole sections]: P = 0.0069). When the whole-tumor sections were observed with EVG staining, all 15 cases without venous invasion showed no recurrence within the observation period. ConclusionsThe addition of EVG staining allowed the identification of venous invasion in patients with colorectal cancer, which eventually affects prognosis. Increasing the number of EVG-stained samples improves the possibility of accurate prediction.

The ability of HALP score to distinguish between malignant and benign colorectal neoplasms and its prognostic importance in colorectal cancers

Systemic inflammation and nutritional status play important roles in the development and progression of various cancers, including colorectal cancer. The prognosis for malignancies can be predicted using the inflammatory marker known as HALP (calculated by hemoglobin, albumin, lymphocytes, and platelets). Furthermore, recent studies have claimed the HALP score to help distinguish between benign and malignant lesions. We aimed to research the diagnostic importance of the HALP score in the differentiation of malignant (colorectal cancer) and benign colorectal neoplasms (colorectal adenomas and hyperplastic polyps) and its prognostic significance in colorectal cancer patients. Patients diagnosed with colorectal cancer, colorectal adenoma, and hyperplastic polyps were evaluated retrospectively between January 2017 and January 2022. The median HALP score in the colorectal cancer group was significantly lower than the other groups (colorectal adenoma and hyperplastic polyps) (p&lt;0.001). There was no statistical difference between the median HALP scores of the colorectal adenoma and hyperplastic groups (p=0.525). ROC analysis found the cut-off value of the HALP score as 41.01 to differentiate colorectal cancer from benign colorectal lesions (sensitivity= 0.73, specitivity=0.62, 95% CI=0.67-0.76, p&lt;0.001). The HALP level below 28.1 was associated with worse overall survival (p=0.046) and was shown to be an independent prognostic factor in the colorectal cancer group. The HALP score can be used to differentiate colorectal cancer from benign colorectal neoplasms and as a prognostic factor in colorectal cancer.

Altered immunoexpression of DNA polymerase delta 1 catalytic subunit (POLD1) in colorectal cancer.

The study aimed to determine the immunoexpression levels of polymerase delta 1 catalytic subunit (POLD1), a catalytic and proofreading subunit of DNA polymerase delta, in the sections of colorectal cancer (CRC), and to evaluate the significance of POLD1 as a potential prognostic factor in CRC. Paired, tumour and non-cancerous tissue samples of the large intestine distant to the neoplasm were collected from the postoperative material of 78 patients who underwent surgical resection of CRC tumours. Polymerase delta 1 catalytic subunit protein levels were determined using immunohistochemistry. Clinical, pathomorphological, and survival data of the patients were pooled. In addition, POLD1 mRNA expression levels of 599 CRC patients were extracted from The Cancer Genome Atlas (TCGA) datasets and subjected to statistical and survival analysis including the Kaplan-Meier method followed by the log-rank test. Immunoexpression of POLD1 was found in the nuclei of the tumour cells and epithelial cells of unchanged intestinal mucosa. Polymerase delta 1 catalytic subunit immunoreactivity in the tumour was heterogenous, and the average immunoreactivity score was decreased in cancer cells when compared to the mucosa of matched sections of unchanged large intestine (p = 0.0259). However, POLD1 expression at the protein and mRNA levels did not associate with clinicopathological characteristics of the patients and their survival. Despite previous studies suggesting that POLD1 genetic alterations could be promising molecular biomarkers in CRC, our results do not support any prognostic significance of POLD1 expression in CRC.

Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis.

KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P < 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742-0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P < 0.001). mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.

Long noncoding RNA 01534 maintains cancer stemness by downregulating endoplasmic reticulum stress response in colorectal cancer.

Studies have shown that cancer stemness and the endoplasmic reticulum (ER) stress response are inversely regulated in colorectal cancer (CRC), but the mechanism has not been fully clarified. Long noncoding RNAs (lncRNAs) play key roles in cancer progression and metastasis. In this study we investigated lncRNA 01534 (LINC01534) as a possible modulator between cancer stemness and ER stress response. In vitro experiments using CRC cell lines were performed to explore a possible role of LINC01534. The expression of LINC01534 in clinical CRC samples was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization. Silencing LINC01534 led to suppression of cell proliferation, invasiveness, and cell cycle progression at the G2-M phase, and promoted apoptosis. Moreover, we found that silencing LINC01534 suppressed cancer stemness, while it activated the ER stress response, especially through the PERK/eIF2α signaling pathway. In situ hybridization revealed LINC01534 was expressed in tumor cells and upregulated in CRC tissues compared with normal epithelium. A survival survey indicated that high LINC01534 expression was significantly associated with shorter overall survival in 187 CRC patients. This is the first report on LINC01534 in human cancer. Our findings suggest that LINC01534 may be an important modulator of the maintenance of cancer stemness and suppression of the ER stress response, and that it could be a novel prognostic factor in CRC.

Preoperative Cancer Inflammation Prognostic Index as a Superior Predictor of Short- and Long-Term Outcomes in Patients with Stage I-III Colorectal Cancer after Curative Surgery.

Inflammatory reactions play a crucial role in cancer progression and may contribute to systemic inflammation. In routine clinical practice, some inflammatory biomarkers can be utilized as valuable predictors for colorectal cancer (CRC). This study aims to determine the usefulness of a novel cancer-inflammation prognostic index (CIPI) marker derived from calculating carcinoembryonic antigen (CEA) multiplied by the neutrophil-to-lymphocyte ratio (NLR) values established for non-metastatic CRCs. Between January 1995 and December 2018, 12,092 patients were diagnosed with stage I to III primary CRC and had radical resection-they were all included in this study for further investigation. There were 5996 (49.6%) patients in the low-CIPI group and 6096 (50.4%) patients in the high-CIPI group according to the cutoff value of 8. For long-term outcomes, the high-CIPI group had a significantly higher incidence of recurrence (30.6% vs. 16.0%, p &lt; 0.001) and worse relapse-free survival (RFS) and overall survival (OS) rates (p &lt; 0.001). High CIPI was an independent prognostic factor for RFS and OS in univariate and multivariate analyses. This research is the first to document the independent significance of CIPI as a prognostic factor for CRC. To ensure that it works, this CIPI needs to be tested on more CRC prediction models.