Unraveling breast cancer prognosis: a novel model based on coagulation-related genes.

Objective: Breast cancer is highly heterogeneous, presenting challenges in prognostic assessment. Developing a universally applicable prognostic model could simplify clinical decision-making. This study aims to develop and validate a novel breast cancer prognosis model using coagulation-related genes with broad clinical applicability. Methods: A total of 203 genes related to coagulation were obtained from the KEGG database, and the mRNA data of 1,099 tumor tissue samples and 572 samples of normal tissue were retrieved from the TCGA-BRCA cohort and GTEx databases. The R package "limma" was utilized to detect variations in gene expression related to coagulation between the malignancies and normal tissue. A model was constructed in the TCGA cohort through a multivariable Cox regression analysis, followed by validation using the GSE42568 dataset as the testing set. Constructing a nomogram incorporating clinical factors to enhance the predictive capacity of the model. Utilizing the ESTIMATE algorithm to investigate the immune infiltration levels in groups with deferent risk. Performing drug sensitivity analysis using the "oncoPredict" package. Results: A risk model consisting of six coagulation-associated genes (SERPINA1, SERPINF2, C1S, CFB, RASGRP1, and TLN2) was created and successfully tested for validation. Identified were 6 genes that serve as protective factors in the model's development. Kaplan-Meier curves revealed a worse prognosis in the high-risk group compared to the low-risk group. The ROC analysis showed that the model accurately forecasted the overall survival (OS) of breast cancer patients at 1, 3, and 5 years. Nomogram accompanied by calibration curves can also provide better guidance for clinical decision-making. The low-risk group is more likely to respond well to immunotherapy, whereas the high-risk group may show improved responses to Gemcitabine treatment. Furthermore, individuals in distinct risk categories displayed different responses to various medications within the identical therapeutic category. Conclusion: We established a breast cancer prognostic model incorporating six coagulation-associated genes and explored its clinical utility. This model offers valuable insights for clinical decision-making and drug selection in breast cancer patients, contributing to personalized and precise treatment advancements.

AGR2: a secreted protein worthy of attention in diagnosis and treatment of breast cancer.

AGR2 is a secreted protein widely existing in breast. In precancerous lesions, primary tumors and metastatic tumors, the expression of AGR2 is increased, which has aroused our interest. This review introduces the gene and protein structure of AGR2. Its endoplasmic reticulum retention sequence, protein disulfide isomerase active site and multiple protein binding sequences endow AGR2 with diverse functions inside and outside breast cancer cells. This review also enumerates the role of AGR2 in the progress and prognosis of breast cancer, and emphasizes that AGR2 can be a promising biomarker and a target for immunotherapy of breast cancer, providing new ideas for early diagnosis and treatment of breast cancer.

Research Progresses in Immunological Checkpoint Inhibitors for Breast Cancer Immunotherapy.

Tumor immune escape refers to the phenomenon in which tumor cells escape the recognition and attack of the body's immune system through various mechanisms so that they can survive and proliferate in vivo. The imbalance of immune checkpoint protein expression is the primary mechanism for breast cancer to achieve immune escape. Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) are critical immune checkpoints for breast cancer. Immune checkpoint inhibitors block the checkpoint and relieve its inhibition effect on immune cells, reactivate T-cells and destroy cancer cells and restore the body's ability to resist tumors. At present, immunological checkpoint inhibitors have made significant progress in breast cancer immunotherapy, and it is expected to become a new treatment for breast cancer.

Open vs. laparoscopic surgery for locally advanced gastric cancer after neoadjuvant therapy: Short-term and long-term survival outcomes.

The aim of the present study was to compare the short-term and long-term survival outcomes of laparoscopic gastrectomy vs. open gastrectomy in treating locally advanced gastric cancer (LAGC) after neoadjuvant therapy. This study retrospectively reviewed the medical records of 270 patients with LAGC, who underwent laparoscopic (n=49) or conventional open (n=221) surgery following neoadjuvant therapy between January 2007 and December 2016 in China National Cancer Center. Postoperative parameters and survival outcomes including overall survival and disease-free survival were analyzed. Patients who underwent laparoscopic gastrectomy (LP) had significantly shorter postoperative stay and a decreased number of metastatic lymph nodes harvested compared to those who underwent open surgery. The 75% disease-free survival (DFS) time in the laparoscopic surgery group (25.7 months) was higher compared with the open surgery group (15.6 months). However, no significant difference was observed in 5-year overall survival and DFS between the two groups. In conclusion, LG provides non-inferior short- and long-term survival outcomes compared with open surgery, suggesting a laparoscopic approach may be justified for patients with LAGC receiving neoadjuvant therapy. More randomized controlled trials are required to investigate the positive effects of LG for LAGC following neoadjuvant therapy.

Long-term survival results of patients with locally advanced gastric cancer and pathological complete response after neoadjuvant chemotherapy and resection.

BACKGROUND: To date, the long-term outcomes of patients with locally advanced gastric cancer (LAGC) who achieved a pathological complete response (pCR) after neoadjuvant therapy are elusive. To evaluate the impact of pCR on the long-term survival of LAGC patients who underwent neoadjuvant therapy and evaluate the necessity of postoperative adjuvant chemotherapy. METHODS: We conducted a retrospective study of clinicopathological and survival data of patients who achieved a pCR after neoadjuvant therapy and resection at the China National Cancer Center between January 2007 and December 2018. RESULTS: Ultimately, 39 patients enrolled in the current study, with a median follow-up time was 30.4 (range 2.5-101.6) months. The 3- and 5-year overall survival (OS) rates were 88.9% and 88.9%, respectively. And the 3- and 5-year disease-free survival (DFS) rates were 88.9% and 88.9%, respectively. During the follow-up, recurrence was observed in 3 patients. Of all 39 patients, 51.3% (n=20) received postoperative adjuvant chemotherapy and 48.7% (n=19) did not. There was no significant difference in OS (P=0.48) and DFS (P=0.47) between patients who underwent postoperative adjuvant chemotherapy and patients who did not. CONCLUSIONS: Patients with LAGC who achieved a pCR after neoadjuvant therapy and resection might have a favorable OS and DFS. Our study failed to demonstrate the benefit of adjuvant chemotherapy for those patients.

Effects of Neoadjuvant Chemotherapy Toxicity and Postoperative Complications on Short-term and Long-term Outcomes After Curative Resection of Gastric Cancer.

BACKGROUND: Whether neoadjuvant chemotherapy (NAC) increased the risk of postoperative morbidities for patients with locally advanced gastric cancer (GC) is unknown. Whether neoadjuvant chemotherapy toxicity (NCT) and postoperative complications (POCs) correlate with short-term and long-term outcomes also remains unclear. We aimed to evaluate the role of NAC on the development of POCs, as well as the impact of NCT and POCs on postoperative and oncologic outcomes in curatively resected GC treated with NAC. METHODS: This study retrospectively reviewed 230 patients who underwent curative gastrectomy for locally advanced GC (clinically T3/4 or N+) after NAC between 2006 and 2016. Five hundred patients undergoing upfront and curative surgery were selected as a control group. After matching, the incidence of POCs was compared between two groups. In the NAC group, clinicopathological characteristics of patients who experienced POCs were compared to those who did not. Logistic and Cox multivariate regression analyses were used to examine factors associated with POCs, disease-free survival (DFS), and overall survival (OS). RESULTS: Following matching, 230 and 230 patients treated with surgery plus NAC and upfront surgery remained, respectively. The incidence of POCs was 28.7% and 24.3%, respectively (p = 0.290). In the NAC group, NCT (OR [odds ratio] 22.968, 95% CI [confidence interval] 2.948-> 99, p = 0.003) and operation time (OR 1.006, 95% CI 1.001-1.011, p = 0.021) were independent predictive factors of POCs. NCT did not affect oncologic outcomes. The Cox regression model demonstrated that POCs were independently associated with worse DFS (HR [hazard ratio] 2.128, 95% CI 1.240-3.653, p = 0.006) but not OS for patients treated with NAC. CONCLUSIONS: The administration of NAC is not associated with an elevated risk of POCs. For patients treated with NAC, NCT is an independent predictor of POCs, but does not affect oncologic outcomes. POCs is independently associated with worse DFS but not OS. NAC should be considered a safe approach in patients who have locally advanced GC. Strategies to minimize chemotherapy toxicity and postoperative morbidities associated with NAC are warranted.

Long-term Results of Conversion Therapy for Initially Unresectable Gastric Cancer: Analysis of 122 Patients at the National Cancer Center in China.

Purpose: To assess the long-term survival and prognostic factors of conversion therapy in patients with initially unresectable gastric cancer. Patients and methods: We conducted a retrospective study of clinicopathological and survival data of 122 consecutive patients who were diagnosed with initially unresectable gastric cancer and underwent the conversion surgery after systemic chemotherapy at the China National Cancer Center between May 2006 and May 2017. Results: For all the 122 patients, the 3- and 5-year overall survival (OS) rates from the date of chemotherapy initiation were 61.0% and 52.0%, respectively, with a median OS of 63.6 months. During follow-up, the recurrence was observed in 49 (40.1%) patients who underwent conversion surgery. According to the multivariate COX regression analysis, receipt of postoperative adjuvant chemotherapy (POAC) was the only significant independent predictor of a favorable OS (HR 0.40; 95% CI 0.18-0.85, P=0.017). Log-rank analysis showed that POAC group experienced a survival advantage in terms of PFS when compared with observation group (HR 0.53, 95%CI 0.31-0.92, P=0.009). Conclusions: Conversion therapy may provide long-term survival for patients with initially unresectable gastric cancer. Postoperative adjuvant chemotherapy might be recommended for patients who underwent conversion therapy.

Clinicopathological Characteristics and Prognosis of Proximal and Distal Gastric Cancer during 1997-2017 in China National Cancer Center.

BACKGROUND: The prognostic relevance of gastric tumor location has been reported and debated. Our study was conducted to examine the differences in clinicopathological features, prognostic factors, and overall survival (OS) between patients with proximal gastric cancer (PGC) and distal gastric cancer (DGC). PATIENTS AND METHODS: Patients with PGC or DGC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1997-2017. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: We reviewed 16,119 cases of gastric cancer patients, including 6,479 of PGC and 9,640 of DGC. PGC patients presented as older patients (61.5 versus 56.4 years, P<0.001) and more males (82.9% versus 68.2%, P<0.001). Compared with DGC, PGC was more likely to be in later pT stage (pT3 and pT4, 65.0% versus 52.8%, P<0.001) and lymph node metastasis (54.8% versus 50.9%, P<0.001). In univariate analysis, PGC patients had a worse survival outcome in stage I (Hazard ratio [HR] = 2.04, 95% CI: 1.42-2.94) but a better prognosis in stage IV (HR = 0.85, 95% CI: 0.73-0.98) when compared to DGC patients. However, multivariate analysis demonstrated that PGC was not an independent predictor for poor survival (HR = 1.07, 95% CI: 1.00-1.14). Results from multivariate analysis also revealed that pT4, lymph node metastasis, distant metastasis, no gastrectomy, and Borrmann IV were independent predictors associated with poor survival for both PGC and DGC patients. Additional prognostic factors for PGC patients included underweight (BMI < 18.5) (HR = 1.29, 95% CI: 1.06-1.58), linitis plastica (HR = 2.13, 95% CI: 1.25-3.65), and overweight (23 ≤ BMI <27.5) (HR = 0.80, 95% CI: 0.71-0.90). During the 20-year study period, the 5-year OS increased significantly for both PGC and DGC, with the increase rate of 91.7% and 67.7%, respectively. CONCLUSION: In China, PGC significantly differed from DGC in clinicopathological characteristics and prognostic factors. However, there was no significant relationship between survival outcome and gastric tumor location.

Long non­coding RNA FER1L4 inhibits cell proliferation and metastasis through regulation of the PI3K/AKT signaling pathway in lung cancer cells.

Lung cancer is among the most common malignancies worldwide; however, the current understanding of its detailed mechanism remains limited. Long non­coding RNAs (lncRNAs) were previously identified to serve significant roles in tumorigenesis. The present study aimed to investigate the role of a novel lncRNA, Fer­1­like family member 4 (FER1L4), in lung tumorigenesis. In the present study, it was demonstrated that the expression level of FER1L4 was significantly decreased in clinical lung cancer tissues and in cultured lung cancer cells, as evidenced by reverse transcription­quantitative polymerase chain reaction analysis. Overexpression of FER1L4 in lung cancer cell lines A549 and 95D inhibited colony formation, cell proliferation and cell migration capacity, measured by colony formation assays, cell proliferation assays and Transwell assays, respectively. Overexpression of FER1L4 led to a reduction in the expression levels of phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt) in A549 and 95D cells, whereas, activation of PI3K/Akt signaling using a small molecular inhibitor of phosphatase and tensin homolog, reversed the inhibitory effects of FER1L4 on cell proliferation and metastasis. All of these results suggested that the lncRNA FER1L4 suppressed cell proliferation and metastasis by inhibiting the PI3K/Akt signaling pathway in lung cancer.

The Significant Influence of the Neuroendocrine Component on the Survival of Patients with Gastric Carcinoma Characterized by Coexisting Exocrine and Neuroendocrine Components.

BACKGROUND: Gastric adenocarcinoma patients with a neuroendocrine (NE) component are frequently observed in routine practice. Several previous studies have investigated the influence of a NE component on the survival of these patients; however, the results were inconsistent. METHODS: We retrospectively investigated a consecutive series of 95 gastric adenocarcinoma patients with a NE component and 190 gastric adenocarcinoma patients without a NE component. We adopted 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% as the cut-off proportions of the NE component, respectively, and analyzed the patients' overall survival according to the proportion of the NE component. RESULTS: The 1-, 3-, and 5-year actual survival rates of the patients with a NE component were 90.1%, 72.3%, and 67.2%, respectively, and for those without a NE component 94.2%, 79.3%, and 75.7%, respectively. The multivariate analysis showed that the patients with NE components >70% (HR: 2.156; 95% CI: 1.011, 4.597; p=0.047) and >90% (HR: 2.476; 95% CI: 1.088, 5.634; p=0.031) had significantly worse survival than those without a NE component. Only the diameter of tumors (>4.64 cm) (HR: 2.585; 95% CI: 1.112, 6.006; p=0.027) and pN3 (HR: 2.953; 95% CI: 1.051, 8.293; p=0.040) were independently associated with worse overall survival for gastric adenocarcinoma patients with a NE component (all p<0.05). CONCLUSION: Gastric adenocarcinoma patients with a NE component >70% and >90% have significantly worse survival than those without a NE component. Only the diameter of tumors and the number of metastatic lymph nodes are independent prognostic factors for gastric adenocarcinoma patients with a NE component.

Development and validation of a nomogram to individually predict survival of young patients with nonmetastatic gastric cancer: A retrospective cohort study.

BACKGROUND/AIMS: Evidence regarding gastric cancer (GC) patients <40 years old is limited. The aim of the study was to identify risk factors affecting overall survival (OS) of young patients with nonmetastatic GC and to establish a nomogram for prognostic prediction using data from the Surveillance, Epidemiology and End Results (SEER) database. Furthermore, this study sought to externally validate this nomogram in an independent patient cohort. PATIENTS AND METHODS: In this retrospective cohort study, the records of patients aged <40 years with nonmetastatic GC (n = 559), from the SEER database, between 2006 and 2015, were examined. The nomogram was established based on the Cox proportional hazards regression model using the SEER dataset. Patients with nonmetastatic GC (n = 201) in our department between 2009 and 2015 were selected as an external validation set. Discrimination and calibration were performed in both cohorts. RESULTS: The multivariate Cox model identified race, tumor subsites, tumor size, depth of invasion, lymph node metastasis, number of examined lymph nodes, and surgery as independent covariates associated with OS. The nomogram exhibited superior discriminative power than the eighth tumor, node, metastasis (TNM) staging system in both the training set [Harrell's concordance index (C index): 0.762 vs. 0.635,P < 0.001] and validation set (C index: 0.805 vs. 0.712,P= 0.176). Calibration of the nomogram was good in both cohorts. CONCLUSIONS: We developed a nomogram predicting 3- and 5-year OS rates in young patients with nonmetastatic GC. Both the training set and validation set showed good discrimination and calibration, suggesting good clinical applicability.

Clinicopathologic features, surgical treatments, and outcomes of small bowel tumors: A retrospective study in China.

BACKGROUND: Small bowel tumors are relatively rare. Accumulation of data regarding their clinical presentation, pathologic features, prognostic factors, treatment modalities, and outcome has been an issue. We summarize the clinicopathologic features and evaluate the long-term outcome of patients with small bowel tumors who underwent surgery. METHODS: This is a retrospective study of medical records of 456 patients with small bowel tumors treated surgically at a Cancer Hospital between 1999 and 2016. RESULTS: The study included 275 males (60.3%) and 181 females (39.7%). Small bowel tumors were difficult to diagnose because of non-specific symptoms. The most common symptoms were alimentary symptoms (56.8%) and abdominal pain (37.3%). Final histopathology revealed 241 adenocarcinomas (52.9%), 153 gastrointestinal stromal tumors (GISTs; 33.6%), 16 neuroendocrine tumors (NETs; 3.5%), and 46 other types of tumors (10.1%). The 456 surgeries performed included 153 pancreaticoduodenectomies, 241 limited duodenum resections, 60 palliative bypass surgeries, and 2 abdominal explorations. The 5-year overall survival and progression-free survival rates for patients with small bowel tumor were 57.2% and 44.6%, respectively. Adenocarcinomas resulted in the worst overall survival compared to GISTs or NETs, and tumors with duodenal location resulted in a worse survival compared to those with non-duodenal location. CONCLUSION: Surgery is the mainstay of treatment for small bowel tumors. Adenocarcinomas and duodenal involvement seem to contribute to poor outcomes.