IDO1/COX2 Expression Is Associated with Poor Prognosis in Colorectal Cancer Liver Oligometastases.

BACKGROUND: IDO1 and COX2 have emerged as promising immunotherapy targets. It is unclear whether IDO1 and COX2 expression levels in colorectal cancer (CRC) patients with liver oligometastases could be independent predictors of overall survival (OS) and progression-free survival (PFS). The purpose of this study was to investigate the correlation of IDO1 and COX2 expression levels with OS and PFS in CRC patients with liver oligometastases. METHODS: The expression levels of IDO1 and COX2 were assessed by immunohistochemistry in 107 specimens from patients with liver oligometastases. The correlation between the expression of IDO1 and COX2 and the clinicopathological parameters and OS/PFS in patients was examined. RESULTS: The expression level of IDO1/COX2 was significantly correlated with age and was not associated with gender, BMI, T stage, N stage, primary tumor size, liver metastasis size, CEA, CA19-9, CD3 TILs or CD8 TILs. In univariate analysis, we found that IDO1/COX2 expression, CEA and N stage all yielded significantly poor OS and PFS outcomes. In our multivariate Cox model, IDO1/COX2 coexpression, CEA and N stage were found to be significantly correlated with OS; IDO1/COX2 coexpression and CEA were significantly correlated with PFS. CONCLUSIONS: IDO1/COX2 coexpression plays a pivotal role and may act as a potential prognostic biomarker for survival in CRC patients with liver oligometastases.

Prognostic and predictive value of Immunoscore and its correlation with ctDNA in stage II colorectal cancer.

This study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low (P < .001). In the multivariate Cox analysis, IS was the only significant parameter associated with DFS. IS-Int and IS-Low patients with adjuvant chemotherapy had improved DFS compared to those who did not receive adjuvant chemotherapy (HR = 0.3; 95% CI 0.1-0.92; P = .026). Among the 49 patients with postoperative ctDNA data, IS-High patients had the lowest ctDNA positivity rate, suggesting that they were most eligible for chemotherapy-free treatment. IS had a strong prognostic value in Chinese patients with stage II CRC and demonstrates its clinical utility. IS and ctDNA will jointly optimize the adjuvant treatment strategies for early-stage CRC.

Case report: Reproductive organ preservation and subsequent pregnancy for an infertility patient with lynch syndrome-associated synchronous endometrial cancer and colon cancer after treatment with a PD-1 checkpoint inhibitor.

Currently, immune checkpoint inhibitors (ICIs) are the mainstay of treatment for Lynch syndrome patients. However, the tumor regression features in radiology and pathology are inconsistent for patients who are treated with ICIs, which sometimes confuses surgical decision-making. Here, we report a case in which a 36-year-old patient suffering from infertility was diagnosed with Lynch syndrome-associated synchronous endometrial cancer and colon cancer, and persistently enlarged left iliac paravascular lymph nodes were detected after receiving sintilimab treatment, a programmed cell death 1 (PD-1) receptor inhibitor. Fortunately, when she was about to undergo hysterectomy and bilateral salpingo-oophorectomy, intraoperative pathology examination did not reveal any cancer cells in these lymph nodes, and therefore, her reproductive organs were preserved. Later, the patient successfully conceived and gave birth to a healthy male neonate with no immune-related adverse events (irAEs) during an 11-month follow-up. This case indicates that surgeons should carefully inspect the imaging characteristics after immunotherapy and that organ preservation is possible even for patients who fail to achieve complete clinical regression, which is especially important for female patients of childbearing age.

Identification of Tumor Microenvironment-Related Alternative Splicing Events to Predict the Prognosis of Endometrial Cancer.

BACKGROUND: Endometrial cancer (EC) is one of the most common female malignant tumors. The immunity is believed to be associated with EC patients' survival, and growing studies have shown that aberrant alternative splicing (AS) might contribute to the progression of cancers. METHODS: We downloaded the clinical information and mRNA expression profiles of 542 tumor tissues and 23 normal tissues from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was carried out on each EC sample, and the OS-related different expressed AS (DEAS) events were identified by comparing the high and low stromal/immune scores groups. Next, we constructed a risk score model to predict the prognosis of EC patients. Finally, we used unsupervised cluster analysis to compare the relationship between prognosis and tumor immune microenvironment. RESULTS: The prognostic risk score model was constructed based on 16 OS-related DEAS events finally identified, and then we found that compared with high-risk group the OS in the low-risk group was notably better. Furthermore, according to the results of unsupervised cluster analysis, we found that the better the prognosis, the higher the patient's ESTIMATE score and the higher the infiltration of immune cells. CONCLUSIONS: We used bioinformatics to construct a gene signature to predict the prognosis of patients with EC. The gene signature was combined with tumor microenvironment (TME) and AS events, which allowed a deeper understanding of the immune status of EC patients, and also provided new insights for clinical patients with EC.

Correlation of gestational hypertension with abnormal lipid metabolism, insulin resistance and D-dimer and their clinical significance.

Correlation of gestational hypertension with abnormal lipid metabolism, insulin resistance and D-dimer were investigated. Seventy-three patients with gestational hypertension in Jinhua People's Hospital were selected as the observation group and 70 healthy gestational subjects were selected as the control group. The indexes of lipid metabolism, insulin resistance index [homeostasis model assessment (HOMA)] and the level of D-dimer in the two groups were compared and the correlation of gestational hypertension with the changes in lipid metabolism, insulin resistance and D-dimer was analyzed. The level of HDL-C (high-density lipoprotein cholesterol) in the observation group was significantly lower than that in the control group (P<0.05), while the levels of other indexes were all significantly higher than those in the control group (P<0.05). HOMA index and D-dimer in the observation group were both significantly higher than those in the control group (P<0.05). TG was positively correlated with gestational hypertension (r=0.8767, P<0.01). The correlation analysis of HOMA and gestational hypertension showed positive correlation (r=0.8819, P<0.01). In addition, D-dimer was positively correlated with gestational hypertension (r=0.8933, P<0.01). Lipid metabolism indexes are abnormal in patients with gestational hypertension as well as for insulin resistance index and D-dimer. Besides, the above-mentioned indexes are all correlated with the patients with gestational hypertension. Therefore, more observations should be made on lipid metabolism indexes, insulin resistance and D-dimer in the future treatment of gestational hypertension.