Erratum: A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.

[This corrects the article DOI: 10.1016/j.omtn.2017.07.005.].

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

Association of perioperative allogeneic blood transfusions and long-term outcomes following radical surgery for gastric and colorectal cancers: systematic review and meta-analysis of propensity-adjusted observational studies.

BACKGROUND: Previous meta-analyses reporting significant associations between perioperative allogeneic blood transfusions and poor prognosis in gastric cancer or colorectal cancer had a high risk of confounding bias. This meta-analysis explored this issue using observational studies that applied propensity score analysis. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for manuscripts published between 2013 and 2022. Studies applying propensity score analysis were included to investigate the association between perioperative allogeneic blood transfusions and prognosis in gastric cancer or colorectal cancer after radical surgery. Pooled HRs for overall survival and disease-free survival were calculated using a fixed-effect model or random-effect model according to heterogeneity. RESULTS: Twelve retrospective cohort studies with 17 607 patients reported were included. Ten studies applied propensity score matching and two applied inverse probability of treatment weighting using propensity score. A total of 5962 patients were analysed after propensity score adjustment. After propensity score adjustment, perioperative allogeneic blood transfusions did not correlate with disease-free survival in gastric cancer (HR 1.16; 95 per cent c.i. 0.96-1.39; heterogeneity was assessed by the chi-squared test and inconsistency index (I2) = 57 per cent) or colorectal cancer (HR 1.12; 95 per cent c.i. 0.84-1.49; I2 = 54 per cent). However, after propensity score adjustment, perioperative allogeneic blood transfusions were significantly associated with worse overall survival in gastric cancer (HR 1.20; 95 per cent c.i. 1.08-1.32; I2 = 25 per cent) and colorectal cancer (HR 1.40; 95 per cent c.i. 1.06-1.85; I2 = 52 per cent). Subgroup analyses showed that perioperative allogeneic blood transfusions did not correlate with overall survival in colorectal cancer when major postoperative complications were balanced after propensity score. CONCLUSION: Perioperative allogeneic blood transfusion is not correlated with recurrence of gastric cancer and colorectal cancer. Perioperative allogeneic blood transfusions are significantly associated with worse overall survival in gastric cancer and colorectal cancer, which may be attributable to unbalanced major postoperative complications after propensity score adjustment.

Evaluation of the prognostic value of negative to positive lymph node ratio in gastric cancer: results from multi-institutional cohorts from western and eastern datasets - Cohort study.

Lymph node (LN) stage is important for prognosis evaluation of gastric cancer (GC) patients. This study aimed to evaluate the prognostic value of the ratio of negative to positive LNs (Rnp) in GC. Methods: The authors evaluated the clinical significance of the Rnp stage in 7660 GC patients from three high-volume institutions in China. Meanwhile, the authors verified the value of the Rnp stage in 11 234 GC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Results: The patients were stratified into different subgroups based on the N stage of the eighth edition of the TNM staging system, the ratio of positive to detected LNs (Rpd) and Rnp. The survival analysis showed clear differences between the three LN stages in both the China and Surveillance, Epidemiology, and End Results cohorts. In univariate and multivariate analyses, the Rnp stage provided smaller Akaike information criterion or Bayesian information criterion values and a larger likelihood ratio χ2 than the N or Rpd stages in both two cohorts. For patients with inadequate examined LNs (<16), the Rnp stage showed better prognostic evaluation performance than the other two stages. In addition, the 5-year disease-specific survival of GC patients showed a slight variation with increasing LNs in the same subgroup classified by the Rnp or Rpd stages compared to the N stage. Conclusions: Along with the higher prognostic value, the Rnp stage has excellent universality with GC patients compared to the N or Rpd stages. Studies with larger sample sizes are needed to predict the prognosis and provide more precise treatment for GC patients.

Efficacy of neoadjuvant immunotherapy in advanced colorectal cancer: a meta-analysis of cross-sectional studies.

BACKGROUND: Although neoadjuvant immunotherapy is being widely studied, there is no consensus on its efficacy in microsatellite-stable (MSS) or mismatch repair proficient (pMMR) colorectal cancer (CRC). This meta-analysis aimed to evaluate studies on neoadjuvant immunotherapy for advanced CRC to assess its efficacy and provide new clinical guidelines. METHODS: We searched literature databases to identify studies that assessed the efficacy of neoadjuvant immunotherapy in advanced CRC. The outcomes evaluated were pathological complete response (pCR), major pathological response (MPR), R0 resection, and anal preservation rates. Heterogeneity among the included studies was assessed by sensitivity analysis, and publication bias was evaluated using Begg and Egger tests. RESULTS: Eleven articles were included in the analysis. The pCR, MPR, R0 resection, and anal preservation rates reported in these studies were 39 and 49, 97, and 76%, respectively. The MSI-H and MSS groups had pooled pCR rates of 70 and 24%, respectively. The pCR rates for the induction, consolidation, and concurrent immuno-chemoradiotherapy (CRT) subgroups were 43, 33, and 27%, respectively, and those for the single and double immunotherapy subgroups were 34 and 40%, respectively. CONCLUSION: Neoadjuvant immunotherapy combined with CRT is effective in treating MSI-H/dMMR advanced CRC. It could also be a new first-line therapeutic option for MSS/pMMR advanced CRC.

Characterization of RNA modifications in gastric cancer to identify prognosis-relevant gene signatures.

BACKGROUND: Most human genes have diverse transcript isoforms, which mainly arise from alternative cleavage and polyadenylation (APA) at 3' ends. N7-methylguanosine (m7 G) is also an essential epigenetic modification at the 5' end. However, the contribution of these two RNA modifications to the development, prognosis, regulation mechanisms, and drug sensitivity of gastric cancer (GC) is unclear. METHODS: The expression data of 2412 patients were extracted from 12 cohorts and the RNA modification patterns of 20 marker genes were systematically identified into phenotypic clusters using the unsupervised clustering approach. Following that, we developed an RNA modification model (RMscore) to quantify each GC patient's RNA modification index. Finally, we examined the correlation between RMscore and clinical features such as survival outcomes, molecular subtypes identified by the Asian Cancer Research Group (ACRG), posttranscriptional regulation, and chemotherapeutic sensitivity in GC. RESULTS: The samples were categorized into two groups on the basis of their RMscore: high and low. The group with a low RMscore had a bad prognosis. Moreover, the low RMscore was associated with KRAS, Hedgehog, EMT, and TGF-ß signaling, whereas a high RMscore was related to abnormal cell cycle signaling pathway activation. The findings also revealed that the RMscore contributes to the regulation of the miRNA-mRNA network. Drug sensitivity analysis revealed that RMscore is associated with the response to some anticancer drugs. CONCLUSIONS: The RMscore model has the potential to be a useful tool for prognosis prediction in patients with GC. A comprehensive investigation of APA-RNA and m7 G-RNA modifications may reveal novel insights into the epigenetics of GC and aid in the development of more effective treatment strategies.

Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal cancer: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors have shown promise in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced colorectal cancer (CRC) immunotherapy, and many clinical trials have been conducted. OBJECTIVE: To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in advanced CRC. METHOD: PubMed, Web of Science, Embase, and The Cochrane Library were searched for relevant studies up to September 2021. A retrospective cross-sectional data analysis was performed and Stata 16 software was used for analyses. RESULTS: Sixteen studies including 1503 patients were analyzed. The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, 0.73). The ORR of MSI-H/dMMR advanced CRC was 37% (95% CI 0.25, 0.48) and that of microsatellite stable/mismatch repair proficient (MSS/pMMR) disease was 11% (95% CI 0.06, 0.16). The ORR was 42% in the BRAF mutant subgroup and 19% in the RAS mutant group. The ORR was 14% in the PD-L1 ( +) subgroup and 32% in the PD-L1(-) subgroup. The rate of adverse effects was 85% (95% CI 0.80, 0.91). CONCLUSION: Anti-PD-1/PD-L1 therapy in MSI-H/dMMR advanced CRC was associated with improved survival. Anti PD-1/PD-L1 combined with antiangiogenic drugs, targeted agents, or chemotherapy might be effective in MSS mCRC. Immunotherapy was effective for the BRAF mutant and KRAS/NRAS(RAS) mutant CRC. Low expression of PD-L1 was a potential predictive marker for positive response and outcome. The high incidence of adverse events at 85% was worthy of further investigation. Further analysis with a higher number of high-quality studies is needed to verify the conclusions.

A retrospective analysis of transanal surgical management of 291 cases with rectal foreign bodies.

BACKGROUND: Rectal foreign bodies (RFB) are quite uncommon except in very busy hospitals. Because of their rarity, it is seldom that the treating physicians have a standard approach to the diagnosis, technique of extraction, and post-extraction evaluation. This can be further complicated by the rather extreme variability of size, shape, and texture of the foreign bodies, as well as the potential extent of trauma to the rectum or distal colon. AIM: The objectives of this study were to delineate the demographics, classification of cause, and injury patterns of RFB and to present the results of the transanal surgical management of a large series of RFB. METHODS: We retrospectively collected extensive data from the hospital medical records of the 291 patients who presented with RFB to the emergency department of Shenyang Proctological Hospital (Shenyang, China) from 2012 July to 2020 December. Specifically, demographics, origins and circumstance of the RFB, complications, injuries, anesthesia method, and the results of the transanal surgical management were recorded and analyzed. RESULTS: Of the 291 RFB cases, 225 (77.3%) were male and 66 (22.7%) were female, with a mean age of 53.8 ± 15.5 years (range, 1 ~ 88 years). The circumstances of the RFB were categorized as swallowed, 199 cases (68.4%); self-inserted, 87 (29.9%); and iatrogenic, 5 (1.7%). The proportion of males in the self-inserted RFB group was significantly greater than the swallowed RFB group (t = 31.114, p = 0.000). In the swallowed RFB group, the most common anorectal injuries and pathological changes were the following: penetration into the mucosa (75 cases, 37.7%), perianal or submucosal abscess (27 cases, 13.6%), and penetration into the anal canal (18 cases, 9.0%). In the self-inserted RFB group, 64 (73.6%) of the 87 cases had an intact rectum, whereas 8 (9.2%) had rectal mucosal ulcers and bleeding, and 7 (8%) had rectal lacerations. In the iatrogenic RFB group, 3 cases (60%) had rectal mucosal ulcers and bleeding, and 2 cases (40%) had inflammation of the rectal mucosa. Regarding extraction procedures, in the swallowed group, 187(187/199; 94%) patients underwent a transanal surgical procedure, and all were successful. In the self-inserted group, 82 patients underwent the transanal surgical procedure, and 74 (74/82; 90.2%) were successful whereas it was unsuccessful in the remaining 8 patients (8/82, 9.8%). Three (3/4, 75%) patients with iatrogenic RFB were resolved by the transanal surgical procedure. CONCLUSION: Men were markedly more likely than women to have swallowed RFBs and self-inserted RFBs. No serious damage to the rectum and anus was found in cases of swallowed RFB. Moreover, most surgical operations to remove foreign bodies via the anus were successful in this category of RFB. In contrast, rectal injury was more severe in patients with self-inserted RFB, such as rectal laceration, rectal mucosal ulcer, and bleeding. Moreover, the transanal removal operation in patients with self-inserted RFB had a failure rate of nearly 10%. Thick, long, hard foreign bodies did present a great challenge to the operator. Therefore, if necessary, patients with foreign bodies may need to be promptly referred for transabdominal removal.

Effect of Chemoradiotherapy on the Survival of Resectable Gastric Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) after surgery are necessary to reduce the risk of metastasis and recurrence for resectable gastric cancer (GC) patients. Adjuvant CT and CRT have been proven to significantly improve the prognosis for GC patients, when compared with surgery only. However, it is still unclear whether radiotherapy offers additional survival benefits to advanced gastric cancer (AGC) patients. METHODS: PubMed, Cochrane Library, and Embase databases were systematically searched for eligible studies that compared survival benefits between CRT and CT. The endpoints of this meta-analysis were measured as HR for OS or DFS and 95% CI using fixed- or random-effect models. Additionally, side effects, completed rate, and metastatic risk, were calculated as OR. Subgroup analyses according to clinicopathological factors were presented. RESULTS: A total of 28 eligible studies involving 20,220 patients were included in our study. Of these, 17 studies evaluated the survival benefits of additional radiotherapy on overall survival (OS) of gastric cancer patients, ten reported the impact of CRT on disease-free survival (DFS), and 26 studies showed long-term survival rate. The pooled results were significant (HR for OS 0.84, 95% CI 0.71-0.99; HR for DFS 0.76, 95% CI 0.66-0.89). The subgroup analysis showed that adjuvant CRT increased OS for patients without preoperative treatment; showed similar nausea/vomiting, but an increased risk of neutropenia; reduced the risk of locoregional recurrence; failed to improve OS for lymph node (LN)-positive GC patients; and significantly improved prognosis for R1-treated patients. Of note, DFS was improved in all the subgroups via decreasing the locoregional recurrence. CONCLUSION: Compared with CT, adjuvant CRT can improve survival for advanced gastric cancer patients, with similar nausea/vomiting, but increased risk of neutropenia. Patients without preoperative treatment or with positive surgical margins should be strongly recommended to undergo CRT. Treatment regimens should be carefully decided by doctors based on patients' tolerance, physical status, and reaction to treatment. Moreover, CRT improves the DFS for patients regardless of subgroups, because it significantly reduced the risk of locoregional recurrence.

Pyroptosis is related to immune infiltration and predictive for survival of colon adenocarcinoma patients.

Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients' prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183-3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061-1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.

Correction: Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance.

[This corrects the article DOI: 10.18632/oncotarget.14871.].

LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway.

BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.

Standardizing the classification of gastric cancer patients with limited and adequate number of retrieved lymph nodes: an externally validated approach using real-world data.

BACKGROUND: Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. METHODS: All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N') resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. RESULTS: Significant difference in OS between the Limited and Adequate set (corresponding N0-N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N' classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N'0 = N0adequate + pT1N0M0limited, N'1 = N1adequate + N0limited (excluding pT1N0M0limited), N'2 = N2adequate + N1limited, N'3a = N3aadequate + N2limited, and N'3b = N3badequate + N3alimited). This N' classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN'M system over the 8th AJCC edition and was successfully validated using the SEER dataset. CONCLUSION: The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs.

The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway.

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo. Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.

[Corrigendum] Altered expression of miR­152 and miR­148a in ovarian cancer is related to cell proliferation.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 5D, the data panels selected to represent the 'SKOV3 with miR­148a mimics' and 'SKOV3 with Negative Control' experiments appeared to contain overlapping data, such that they may have been derived from the same original source. The authors have re­examined their original data, and realized how the errors in the compilation of Fig. 5 arose. The corrected version of Fig. 5, showing the correct data for the 'SKOV3 with miR­148a mimics' panel in Fig. 5D and the 'SKOV3 with Negative Control' panel in Fig. 5C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 27: 447-454, 2012; DOI: 10.3892/or.2011.1482].

Tumor budding as a predictor for prognosis and therapeutic response in gastric cancer: A mini review.

In recent years, the role of tumor budding in gastric cancer has received increased attention across a number of disciplines. Several studies have found associations between tumor budding and the prediction of lymph node metastasis in early gastric cancer, prognosis of advanced gastric cancer, predictors of therapeutic response to immune checkpoint inhibitors, such as microsatellite instability (MSI), and therapeutic targets of molecular targeted therapy, such as human epidermal growth factor receptor 2 (HER-2). Therefore, tumor budding is a major element in the formulation of risk stratification and precision medicine strategies for patients with gastric cancer.

Integrative analysis-based identification and validation of a prognostic immune cell infiltration-based model for patients with advanced gastric cancer.

BACKGROUNDS: Advanced gastric cancer (GC) remains difficult to conduct individualized prognostic evaluations owing to the highly heterogeneous nature and the low level of immune cell infiltration (ICI) within GC tumors. This study thus sought to develop a model capable of classifying GC patients according to the degree of tumor ICI and gauging prognosis. METHODS: The degree of ICI in GC patients from the GSE15459, GSE57303, and GSE62254 datasets were estimated, and these values were used to group patients via an unsupervised clustering approach, after which ICI cluster-related genes were identified the association with prognosis through Cox and LASSO regression analyses. The primary risk genes were then verified by immunohistochemical staining of GC tumor tissue samples. RESULTS: 570 patients were clustered into three clusters and 289 ICI cluster-related genes were identified. A prognostic model based on the expression of six crucial ICI risk genes (CXCL11, RBPMS2, LOC400043, JCHAIN, CT83, and ORM1) wa constructed. Patients identified as being high risk based upon the model have poorer clinical features and survival outcomes compared to the other patients. Adjuvant intervention was found to be more beneficial for patients expressing high levels of RBPMS2, JCHAIN, or ORM1. Furthermore, patients expressing low levels of JCHAIN or CT83 in GC tumor tissues were verified to exhibit a significantly better prognosis in a CMU cohort. CONCLUSION: Advanced GC patients were successfully grouped into clusters based on the degree of intratumoral ICI, and a prognostic evaluation model based on 6 ICI risk genes was developed and validated.