Prognosis Of Gastrointestinal Cancer Research Articles

Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma.

Drug resistance is a major challenge in the treatment of advanced cholangiocarcinoma (CCA). Understanding the mechanisms of drug resistance can aid in identifying novel prognostic biomarkers and therapeutic targets to improve treatment efficacy. This study established 5-fluorouracil- (5-FU) and gemcitabine-resistant CCA cell lines, KKU-213FR and KKU-213GR, and utilized comparative proteomics to identify differentially expressed proteins in drug-resistant cells compared to parental cells. Additionally, bioinformatics analyses were conducted to explore the biological and clinical significance of key proteins. The drug-resistant phenotypes of KKU-213FR and KKU-213GR cell lines were confirmed. In addition, these cells demonstrated increased migration and invasion abilities. Proteomics analysis identified 81 differentially expressed proteins in drug-resistant cells, primarily related to binding functions, biological regulation, and metabolic processes. Protein-protein interaction analysis revealed a highly interconnected network involving MET, LAMB1, ITGA3, NOTCH2, CDH2, and NDRG1. siRNA-mediated knockdown of these genes in drug-resistant cell lines attenuated cell migration and cell invasion abilities and increased sensitivity to 5-FU and gemcitabine. The mRNA expression of these genes is upregulated in CCA patient samples and is associated with poor prognosis in gastrointestinal cancers. Furthermore, the functions of these proteins are closely related to the epithelial-mesenchymal transition (EMT) pathway. These findings elucidate the potential molecular mechanisms underlying drug resistance and tumor progression in CCA, providing insights into potential therapeutic targets.

Blockade of CaV3 calcium channels and induction of G0/G1 cell cycle arrest in colon cancer cells by gossypol.

Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.

Phase angle: A robust predictor of malnutrition and poor prognosis in gastrointestinal cancer

ObjectivesThe aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer. MethodsIn total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia. ResultsLow PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409–0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction. ConclusionsPA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer.

The role of lymphocyte-C-reactive protein ratio in the prognosis of gastrointestinal cancer: a systematic review and meta-analysis.

The lymphocyte-to-C-reactive protein (LCR) ratio, an immune-inflammatory marker, shows prognostic potential in various cancers. However, its utility in gastrointestinal malignancies remains uncertain due to inconsistent findings. This systematic review and meta-analysis synthesizes recent evidence to elucidate the association between LCR and prognosis in gastrointestinal cancer patients, aiming to clarify LCR's potential role as a prognostic biomarker. We searched PubMed, Embase, Cochrane, and Web of Science databases up to May 2024 to evaluate the association between LCR and prognosis in gastrointestinal cancer patients. The main outcomes included overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). We also analyzed secondary parameters such as geographical region, study duration, sample size, LCR threshold, and patient characteristics (age, gender, tumor location, and TNM stage). This meta-analysis of 21 cohort studies (n=9,131) finds a significant association between reduced LCR levels and poor prognosis in gastrointestinal cancer. Lower LCR levels were associated with worse overall survival (HR=2.01, 95% CI=1.75-2.31, P<0.001), recurrence-free survival (HR=1.90, 95% CI=1.32-2.76, P<0.001), and disease-free survival (HR=1.76, 95% CI=1.45-2.13, P<0.001). Subgroup analyses by cancer type, timing, and LCR threshold consistently confirmed this relationship (P<0.05). LCR may serve as a prognostic marker in gastrointestinal cancer patients, with lower LCR levels associated with poorer prognosis. However, more high-quality studies are needed to validate these findings, considering the limitations of the current evidence. https://www.crd.york.ac.uk/prospero/, identifier CRD42023486858.

Claudins-Promising Biomarkers for Selected Gastrointestinal (GI) Malignancies?

Despite recent() improvements in diagnostic ability() and treatment() strategies for patients() with neoplastic disease(), gastrointestinal (GI) cancers(), such() as colorectal, gastric, pancreatic, and oesophageal cancers(), are still common() malignancies and the leading() cause() of cancer() deaths worldwide(), with a high frequency of recurrence and metastasis as well as poor patient() prognosis. There is a link() between the secretion of proteolytic enzymes that degrade the extracellular matrix and the pathogenesis of GI tumours. Recent() findings have focused() on the potential() significance() of selected claudins (CLDNs) in the pathogenesis and prognosis of GI cancers(). Tight junctions (TJs) have been proven to play an important role() in maintaining cell() polarity and permeability. A number of authors have recently() revealed that TJ proteins, particularly() selected CLDNs, are related() to inflammation and the development() of various tumours, including GI malignancies. This review() presents general() characteristics and the involvement() of selected CLDNs in the progression() of GI malignancies, with a focus() on the potential() application() of these proteins in the diagnosis() and prognosis of colorectal cancer() (CRC), gastric cancer() (GC), pancreatic cancer() (PC), and oesophageal cancer() (EC). Our review() indicates that selected CLDNs, particularly() CLDN1, 2, 4, 7, and 18, play a significant() role() in the development() of GI tumours and in patient() prognosis. Furthermore, selected CLDNs may be of value() in the design() of therapeutic() strategies for the treatment() of recurrent tumours.

Usefulness of the preoperative inflammation-based prognostic score and the ratio of visceral fat area to psoas muscle area on predicting survival for surgically resected adenocarcinoma of the esophagogastric junction.

Sarcopenic obesity is associated with gastrointestinal cancer prognosis through systemic inflammation. However, in patients with adenocarcinoma of the esophagogastric junction (AEG), the relationship between the inflammation-based prognostic score (IBPS), muscle loss, visceral fat mass, and prognosis has not been sufficiently evaluated. We investigated the prognostic value of the preoperative IBPS and the visceral fat area ratio to the psoas muscle area (V/P ratio) in patients with AEG undergoing surgery. We retrospectively analyzed 92 patients with AEG who underwent surgery. The prognostic value of the preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, systemic inflammation response index, C-reactive protein-to-albumin ratio, prognostic nutritional index, modified Glasgow Prognostic Score, and V/P ratio at the third lumbar vertebra was investigated using univariate and multivariate survival analyses. Multivariate analysis revealed that a high pathological stage (p = 0.0065), high PLR (p = 0.0421), and low V/P ratio (p = 0.0053) were independent prognostic factors for poor overall survival (OS). When restricted to patients with body mass index (BMI) ≥ 25kg/m2, a high V/P ratio was a poor prognostic factor (p = 0.0463) for OS. Conversely, when restricted to patients with BMI < 25kg/m2, a low V/P ratio was a poor prognostic factor (p = 0.0021) for OS. Both PLR and V/P ratios may be useful prognostic biomarkers in surgical cases of AEG. V/P ratio and BMI may provide an accurate understanding of the muscle and fat mass's precise nature and may help predict AEG prognosis.

Comprehensive analysis of cell-extracellular matrix protein Ras suppressor-1 in function and prognosis of gastrointestinal cancers.

Ras suppressor 1 (RSU1), a highly conserved protein, plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion. Aberration of RSU1 activity can cause changes in cell adhesion and migration, thereby enhancing tumor proliferation and metastasis. However, the correlation between RSU1 and gastrointestinal cancers (GICs), as well as its prognostic role related to tumor-infiltrating immune cells (TIICs) remains unclear. To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC. Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter. Then, RSU1-correlated genes were screened and functionally characterized via enrichment analysis. The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource (TIMER). In addition, the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER. High RSU1 expression was associated with poor overall survival of gastric cancer patients, exhibiting a hazard ratio (HR) = 1.36, first progression HR = 1.53, and post progression survival HR = 1.6. Specifically, high RSU1 Levels were associated with prognosis of gastric cancer in females, T4 and N3 stages, and Her-2-negative subtypes. Regarding immune-infiltrating cells, RSU1 expression level was positively correlated with infiltration of CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colorectal adenocarcinoma and stomach adenocarcinoma. RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage, DCs and T cell exhaustion in GICs. In gastrointestinal cancers, RSU1 is increased in tumor tissues, and predicts poor survival of patients. Increased RSU1 may be involved in promoting macrophage polarization, DC infiltration, and T cell exhaustion, inducing tumor immune escape and the development of tumors in GICs. We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs, as well as a potential therapeutic target for precision treatment through improving the immune response.

Intestinal Microbiomes In Gastrointestinal Cancer

The intestinal flora, a crucial system of microorganisms in the human body, is crucial to the immune system, metabolism, and inflammatory response of the body. The intestinal flora is one of them, and as a crucial element of the gastrointestinal microecology, it has a significant impact on the development and spread of gastrointestinal cancer as well as its management. The study of intestinal flora has become more in-depth recently as a result of the quick advancement of high-throughput sequencing technology, and the role of intestinal flora in the development and prognosis of gastrointestinal cancer is becoming increasingly obvious. In this article, the key topics covered include the links between Helicobacter pylori and gastric cancer, as well as the relationship between Fusobacterium and colon cancer, and discusses the mechanism by which intestinal microbes affect the treatment of gastrointestinal cancer. The link between gut microbiota and gastrointestinal cancer was further clarified, and the regulation of gut microbiota was proposed as a new management method for the clinical gastrointestinal cancer treatment.

Expression And Prognostic Role of PRDX1 In Gastrointestinal Cancers.

Esophageal, gastric, liver, and colorectal cancers represent four prevalent gastrointestinal cancers that pose substantial threats to global health due to their high morbidity and mortality rates. Peroxiredoxin 1 (PRDX1), a significant component of the PRDXs family, primarily functions to counteract the peroxides produced by metabolic activities in the body, thereby maintaining the dynamic equilibrium of peroxides in vivo. Intriguingly, PRDX1 expression correlates strongly with cancer's onset, progression, and prognosis. This study mainly applied bioinformatics methods to analyze PRDX1's expression, diagnosis, and prognosis in gastrointestinal cancers and to summarize current research advancements. Evidence from the bioinformatics database suggested that the high expression of PRDX1 was a prominent characteristic of these four gastrointestinal cancers, with this observation reaching statistical significance. The high expression of PRDX1 in gastrointestinal cancer cells also confirms this result. Notably, the primary alteration in PRDX1 within these cancers is the presence of genetic mutations. PRDX1 demonstrated the highest diagnostic efficacy for colorectal cancer. Nevertheless, elevated PRDX1 levels only significantly diminished the survival time of liver cancer patients, exerting no statistically significant impact on the survival duration of patients afflicted by the other three types of gastrointestinal cancers. Recent research has indicated variability in PRDX1 expression across different cancer types, with high expression being predominantly observed in these four gastrointestinal cancers and, in most instances, unfavorable prognosis. These findings broadly align with the results derived from bioinformatics. This research underscores the high expression of PRDX1 in gastrointestinal cancers, its relevance to the diagnosis and prognosis monitoring of these cancers, and its potential to guide clinical treatment for these cancers.

Prevalence and survival of gastrointestinal malignancies with brain metastasis: Surveillance, Epidemiology, and End Results SEER database analysis 2010-2018.

e14004 Background: Gastrointestinal (GI) cancers are amongst the leading causes of cancer-related death worldwide. GI cancers with brain metastasis on presentation are rare; however, the oncologist will intermittently encounter such patients. Unfortunately, there is a paucity of data to inform the prevalence and prognosis of GI cancers with brain metastasis, especially in light of therapeutic developments in the past decade and whether that might have influenced the survival. In this study, we measured the prevalence of brain metastasis secondary to primary GI malignancies at the time of diagnosis, the observed median survival, and Kaplan-Meier 2-years overall survival. The aim is to highlight the burden and prognosis of this population. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) Program 18 registry (2010-2018) database. We identified the total number of patients and patients with brain metastasis at the time of diagnosis for the following gastrointestinal cancers: esophagus, stomach, pancreas, colon, rectum, liver, intrahepatic biliary duct, and gallbladder. We obtained the prevalence, the observed median survival, and the 2-years survival using the Kaplan-Meier method. Results: The total number of cases, prevalence, median survival, and 2-years overall survival are shown in the table. The prevalence of brain metastasis at diagnosis was highest for esophageal cancer at 1.41%, followed by stomach 0.52%, and gall bladder 0.37%. The lowest incidence was small intestinal cancers at 0.13%. The median survival was short, ranging between 2 to 4 months for all studied cancers except for the small intestine and rectum at about six months. Kaplan-Meier 2-years survival was highest for the small intestine at 17%, and the worst was gallbladder, where no one survived at the end of the 24 months. Conclusions: Brain metastasis at the time of diagnosis of GI cancer remains rare. However, its presence portends an abysmal prognosis of 2-4 months. This study helps to inform the practicing oncologist of the current prevalence and prognosis of GI malignancies with brain metastasis on presentation. In addition, these findings encourage prompt involvement of palliative care, setting realistic expectations, and discussing goals of care once such a grave diagnosis is made.[Table: see text]

ACYP1 Is a Pancancer Prognostic Indicator and Affects the Immune Microenvironment in LIHC.

BackgroundACYP1 plays important physiological and metabolic roles in glycolysis and membrane ion pump activity by catalyzing acyl phosphate hydrolysis. ACYP1 is related to tumorigenesis and progression and poor prognosis in gastrointestinal cancer. However, its pancancer roles and mechanisms are unclear. Our study aimed to understand the ACYP1 expression signature and prognostic value across cancers and investigate immune infiltration patterns in liver hepatocellular carcinoma (LIHC) and verify them in LIHC samples.MethodsTranscriptional expression profiles of ACYP1 across cancers were analyzed using Oncomine and TIMER. The prognostic value of ACYP1 was assessed across PrognoScan, Kaplan—Meier Plotter, and GEPIA. Significant pathways associated with ACYP1 in LIHC were obtained via Gene Set Enrichment Analysis. The correlation between ACYP1 expression and immune infiltration in LIHC was investigated using TIMER. We validated ACYP1 expression, prognostic value, and association with immune cells in tumor tissues by immunohistochemistry and flow cytometry.ResultsACYP1 was overexpressed across cancers. High expression of ACYP1 correlated with a poor prognosis in most tumor types, especially in LIHC. ACYP1 was significantly implicated in immune and metabolic related pathways. High ACYP1 expression showed significant correlations with the abundances of Th2 cells, Tregs, macrophages, dendritic cells, and myeloid-derived suppressor cells in LIHC. LIHC patients with high ACYP1 expression showed significantly shorter overall survival and relapse-free survival rates concomitant with increased infiltration of CD4+ T cells. Mouse subcutaneous tumors with ACYP1 overexpression exhibited significantly accelerated tumor progression with increased aggregation of CD4+ T cells.ConclusionOverall, ACYP1 may serve as a vital prognostic biomarker and play an immunoregulatory role in LIHC.

The Roles of Mesenchymal Stem Cells in Gastrointestinal Cancers.

Mesenchymal stem cells (MSCs) were reported to have strong immunomodulatory ability, and inhibit the proliferation of T cells and their immune response through cell-to-cell interactions and the generation of cytokines. With high differentiation potential and self-renewal ability, MSCs are considered to function in alleviating inflammatory responses, promoting tissue regeneration and inhibiting tissue fibrosis formation. As the most common malignancies, gastrointestinal (GI) cancers have high incidence and mortality. The accurate diagnosis, exact prognosis and treatment of GI cancers have always been a hot topic. Therefore, the potential applications of MSCs in terms of GI cancers are receiving more and more attention. Recently, there is increasing evidence that MSCs may serve as a key point in the growth, metastasis, inhibition, treatment and prognosis of GI cancers. In this review, we summarized the roles of MSCs in GI cancers, mainly focusing on esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), colorectal cancer (CRC) and pancreatic cancer. Besides, we proposed MSCs as potential targets and treatment strategies for the effective treatment of GI cancers, which may provide better guidance for the clinical treatment of GI cancers.

Identification of Potential Immune-related Biomarkers in Gastrointestinal Cancers

Objectives: Gastrointestinal (GI) cancer is the most common and lethal malignant tumor, while limited research and biomarkers are available to stratify patients who are likely to benefit from immunotherapy in GI cancers. During early diagnosis and prognosis of GI cancers, searching for shared potential biomarkers and differences among stages is an urgent and challenging task. The staging RNA expression data corresponding to immune genes were analyzed to infer the immune system in each stage of GI cancers. Methods: The differential expression gene analysis was performed to analyze the expression of 758 immune genes between normal and each stage samples of GI cancers. Enrichment analysis including GO and KEGG pathway analysis was carried out to investigate the role of these differential genes and underlying mechanisms in GI cancers. Furthermore, PPI network analysis recognized the hub genes among these DEGs. Overall survival analysis was processed to clarify the diagnostic and prognostic role of these potential biomarkers in early and advanced stages. Results: Our present work revealed the immunological commonness and differences across stages of GI cancers, and disclosed several potential immune-related biomarkers, including CCL20, C7, CD36, CXCL11, and CLEC5A. The potential biological function which immune system participates across the GI cancers was highly correlated with virus and membrane. Conclusions: Our result facilitates to understand the involvement of immune system in GI cancers and better design treatment strategies based on current cancer immunotherapy.

Expression of Four Autophagy-Related Genes Accurately Predicts the Prognosis of Gastrointestinal Cancer in Asian Patients.

Gastrointestinal (GI) cancers are among the most fatal diseases in the world. Numerous studies have demonstrated the relationship between autophagy and development of gastrointestinal cancers. However, whether autophagy-related genes can predict prognosis of GI cancers in individuals of Asian ancestry has not been defined. This study, evaluated the prognostic value of autophagy-related genes in gastrointestinal cancer. Expression profile of autophagy-related genes for 296 gastrointestinal cancer patients of Asian ancestry was downloaded from the TCGA database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL, and TCGA-READ). The prognostic value of the autophagy-related genes was evaluated using univariate Cox, LASSO, and multivariate Cox regression analyses. The risk score of the autophagy-related gene signature was calculated to assess its predictive prognostic value for GI cancers. Forty-seven differentially expressed autophagy-related genes, in Asian patients with gastrointestinal cancers, were identified. Of the 47 genes, 4 were associated with prognosis of GI cancer (SQSTM1, BIRC5, NRG3, and CXCR4). A prognostic model for GI cancer, based on the expression of the above 4 genes in the training set, showed that cancer patients were stratified into high-risk and low-risk groups (P < 0.05). The utility of the model for overall survival (OS) of GI cancer patients was consistent across the entire set, training set, and test set (entire set: P = 4.568 × 10−4; train set: P = 5.718 × 10−3; test set: P = 3.516 × 10−2). The sensitivity and specificity of the ROC curve of the above prognostic model in predicting the 5-year prognosis of GI cancer was satisfactory (entire set: 0.728; train set: 0.727; test set: 0.733). Analysis of clinical samples validated the overexpression of the 4 genes (SQSTM1, BIRC5, NRG3, and CXCR4) in tumor tissues relative to paired normal tissues, consistent with bioinformatic findings. Expression of the 4 autophagy-related genes (SQSTM1, BIRC5, NRG3, and CXCR4) can accurately predict the prognosis of gastrointestinal tumors in Asian patients.

Prognostic effect of sarcopenia in colorectal cancer recurrence

ObjectivesNutritional status significantly influences postoperative prognosis in gastrointestinal cancers. It has been evaluated using sarcopenia before treatments such as surgery and chemotherapy, despite constant changes in nutritional status. We consider that nutritional status at cancer recurrence is one of the important factors that affect treatment choice and intensity. This study evaluated the prognostic effects of improved postoperative nutritional status for people with colorectal cancer recurrence. MethodsWe enrolled 209 participants with pathologically confirmed stage II or III colorectal cancer who underwent radical resection. Sarcopenia was diagnosed using the psoas muscle index obtained from analysis of three-dimensional computed tomographic images. We adopted the cutoff value that was proposed by Hamaguchi et al. (psoas muscle index < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women). Evaluation was performed before surgery and at the time of recurrence. Participants with preoperative sarcopenia who relapsed were divided into two groups at the time of recurrence: sarcopenia continuation and sarcopenia improvement. We compared the prognosis of the two groups and examined the effect of postoperative nutritional improvement. ResultsAmong the 209 participants, 81 (38.8%) had preoperative sarcopenia; this group had significantly lower overall survival than those without sarcopenia (P = 0.028). Colorectal cancer recurred in 48 participants. Of those 46, sarcopenia was evaluated at the time of recurrence; 19 of those 46 had preoperative sarcopenia. Preoperative sarcopenia did not affect the cancer recurrence ratio (sarcopenia, 23.5%; non-sarcopenia, 21.3%; P = 0.893). The sarcopenia-improvement group had higher overall survival than the sarcopenia-continuation group (P = 0.042). ConclusionsAmong participants with preoperative sarcopenia, the prognosis at the time of recurrence improved for the sarcopenia-improvement group compared to the sarcopenia-continuation group. In people with colorectal cancer and sarcopenia, nutritional management is important not only before but also after surgery.

CALD1 is a prognostic biomarker and correlated with immune infiltrates in gastric cancers

BackgroundCaldesmon gene (CALD1) plays an important role in many cellular functions. Some researchers have found the correlation between CALD1 expression and prognosis of gastrointestinal cancer (GI), but the association with tumor-infiltrating lymphocytes (TILs) still unclear. MethodsThe expression of CALD1 in different human tumor was analyzed by Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The correlations between CALD1 and prognosis in types cancer were explored by Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The association between CALD1 expression and tumor immune cell infiltration was further analyzed via TIMER and GEPIA databases. ResultsThe CALD1 expressions in types cancer between tumor tissues and adjacent normal tissues were significantly different. The high expression of CALD1 was related with poor overall survival (OS) of patients with gastric cancer, especially in gastric cancer patients at N1, N2 and N3 stages. The expression of CALD1 was positively associated with immune-infiltrated, such as CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells (DCs) in gastric cancer. ConclusionsCALD1 was considerably a key role in prognosis of patients with gastric cancer. The expression level of CALD1 is significantly associated with immune-infiltrated in gastric cancer. Furthermore, CALD1 expression may be involved in regulating tumor-associated macrophages (TAMs), dendritic cells, exhausted T cells and regulatory T cells in gastric cancer. These findings suggest that CALD1 could be utilized as a marker of prognosis and immune infiltration in gastric cancer.

A novel prognosis marker based on combined preoperative carcinoembryonic antigen and systemic inflammatory response for resectable gastric cancer.

Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer.Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated.Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set.Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.

The role of HMGB1 in gastrointestinal cancers

Despite advances in diagnostic and therapeutic methods, gastrointestinal (GI) cancers have both a high incidence and a high mortality rate. In addition to surgery, chemotherapy and radiotherapy, novel modalities such as immunotherapy are increasingly used in the treatment of these cancers. However, the prognosis in GI cancers remains poor despite the availability of these treatments, which prompted the search for new prognostic and predictive markers. High-mobility group box-1 (HMGB1) is a non-histone DNA protein which is known as a nuclear transcription factor. The search for new therapeutic targets has also gained importance. In this review, the prognostic and predictive role of HMGB1 in gastrointestinal cancers will be discussed in light of current literature.

Abstract 2150: CD103+ tumor infiltrating lymphocytes predict a favorable prognosis in human colorectal cancer

Abstract Background: Given that immune system maintains homeostasis by excluding tumors with mutations, in recent years has been proposed the "cancer-immunoediting" hypothesis, which divides immune responses into three phases, i.e., exclusion, equilibrium, and escape. This equilibrium phase takes likely several decades in human life, during the occurrence of mutations and growth of tumors. Recent studies have emerged that the resident memory T cells (Trm) exclusively survey the transformation of normal tissues in equilibrium phase, though reported were other two memory T subsets in extra-epithelial organs, such as central memory T (Tcm) and effector memory T (Tem) cells. Notably, Trm does not exit into blood circulation, instead exerts powerful ant-tumor functions as tumor infiltrating T cells (TIL), by the expression of unique molecules such as CD69 and CD103; CD69 restricts residence in epithelial tissues, and CD103 bounds to a cognate ligand, epithelial E-cadherin, to stimulate antitumor effect. Purpose: Although previous reports suggested Trm involvement in several tumors, the significance of Trm in predictive patient prognosis of gastrointestinal cancer remains to be investigated fully. Here we study the significance of Trm in colorectal cancer. Materials and Methods: All available patients of hundred-twenty patients with colorectal cancer in Osaka University Hospital were enrolled in this study during 2012 to 2013, under the agreement of written informed consents; the study was performed according to the approval of institutional ethical committee. Immunohistochemistry by staining tissue samples from surgically resected specimens was performed to identify the cellular distribution, number and expression intensity of CD103+/CD69+ in CD8+ lymphocytes, infiltrated in colorectal cancer tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to predict overall and recurrence-free survival in all patients with colorectal cancer examined. Result: The staining of Trm, i.e., intratumor CD103+/CD69+/CD8+ TILs represented a favorable prognostic predictor of overall and recurrence-free survival (p&amp;lt;0.05). Indeed, CD103+ TILs were positively associated with the expression of E-cadherin in intratumor regions of colorectal cancer tissues. Conclusions: The present study suggests that Trm has a significant role in tumor immunity by expressing CD103 in intratumor regions of colorectal cancer tissues, indicating that CD103+ TILs will be useful for the prediction of patient' survival after surgery of colorectal cancer. Citation Format: Masatoshi Kitakaze, Masamitsu Konno, Taroh Satoh, Tsunekazu Mizushima, Yuichiro Doki, Hideshi Ishii. CD103+ tumor infiltrating lymphocytes predict a favorable prognosis in human colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2150.