BackgroundThe prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) are indicators of nutritional immune status. They have been reported associated with clinical outcomes of various solid tumors. However, it is unclear whether they can serve as predictors for patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) receiving immunotherapy. Our objective was to study the prognostic value of PNI and SII in these patients.MethodsSeventy-five MSI-H mCRC patients were enrolled in our study. Logistic regression analysis was used to identify features that influenced immunotherapy response. Survival differences between groups of mCRC patients were compared using the Kaplan–Meier method and log-rank test. The independent risk parameters for progression-free survival (PFS) and overall survival (OS) of patients with MSI-H mCRC were established by Cox proportional risk regression analysis.ResultsThe optimal SII and PNI cutoff values were 409.6 and 51.35. Higher PNI (p = 0.012) and lower high-density lipoprotein cholesterol (HDLC, p = 0.012) were associated with a better immunotherapy response. SII (p = 0.031), cholesterol (CHO) (p = 0.007) and aspartate aminotransferase (AST) (p = 0.031) were independent prognostic factors correlated with OS. Higher PNI (p = 0.012) and lower AST (p = 0.049) were negative predictors of PFS. In addition, patients suffered from immune-related adverse events (irAEs) had a lower SII level (p = 0.04).ConclusionHigher AST and SII, and lower PNI predict worse outcomes in MSI-H mCRC patients undergoing immunotherapy. Moreover, patients with lower SII before immunotherapy suffered from irAEs more often.

AimsAs sex hormone-dependent tumors, it remains to be clarified whether there is a common genetic signature and its value between breast and endometrial cancers. The aim of this study was to establish the shared sex hormone metabolism-related gene prognostic index (SHMRGPI) between breast and endometrial cancers and to analyze its potential role in the therapeutic and prognostic assessment of endometrial cancers.MethodsUsing transcriptome data from TCGA, tumor-associated gene modules were identified by weighted gene co-expression network analysis, and the intersection of module genes with female sex hormone synthesis and metabolism genes was defined as sex hormone metabolism-related gene. SHMRGPI was established by the least absolute shrinkage and selection operator and Cox regression. Its prognostic value of patients with endometrial cancer was validated, and a nomogram was constructed. We further investigated the relationship between SHMRGPI groups and clinicopathological features, immune infiltration, tumor mutation burden, and drug sensitivity.ResultsA total of 8 sex hormone metabolism-related gene were identified as key genes for the construction of prognostic models. Based on SHMRGPI, endometrial cancer patients were divided into high and low SHMRGPI groups. Patients in the low SHMRGPI group had longer overall survival (OS) compared with the high group (P< 0.05). Furthermore, we revealed significant differences between SHMRGPI groups as regards tumor immune cell infiltration, somatic mutation, microsatellite instability and drug sensitivity. Patients with low SHMRGPI may be the beneficiaries of immunotherapy and targeted therapy.ConclusionsThe SHMRGPI established in this study has prognostic power and may be used to screen patients with endometrial cancer who may benefit from immunotherapy or targeted therapy.

AimsThe findings in epidemiological studies suggest that endometrioid endometrial cancer (EEC) is associated with obesity. However, evidence from gene expression data for the relationship between the two is still lacking. The purpose of this study was to explore the merits of establishing an obesity-related genes (ORGs) signature in the treatment and the prognostic assessment of EEC.MethodsMicroarray data from GSE112307 were utilized to identify ORGs by using weighted gene co-expression network analysis. Based on the sequencing data from TCGA, we established the prognostic ORGs signature, confirmed its value as an independent risk factor, and constructed a nomogram. We further investigated the association between grouping based on ORGs signature and clinicopathological characteristics, immune infiltration, tumor mutation burden and drug sensitivity.ResultsA total of 10 ORGs were identified as key genes for the construction of the signature. According to the ORGs score computed from the signature, EEC patients were divided into high and low-scoring groups. Overall survival (OS) was shorter in EEC patients in the high-scoring group compared with the low-scoring group (P < 0.001). The results of the Cox regression analysis showed that ORGs score was an independent risk factor for OS in EEC patients (HR = 1.017, 95% confidence interval = 1.011–1.023; P < 0.001). We further revealed significant disparities between scoring groups in terms of clinical characteristics, tumor immune cell infiltration, and tumor mutation burden. Patients in the low-scoring group may be potential beneficiaries of immunotherapy and targeted therapies.ConclusionsThe ORGs signature established in this study has promising prognostic predictive power and may be a useful tool for the selection of EEC patients who benefit from immunotherapy and targeted therapies.

Although the use of regorafenib plus nivolumab demonstrates promising outcomes in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC), other studies failed to observe such an effect. In addition, a comparison between regorafenib combined with programmed cell death protein 1 (PD-1) antibodies and regorafenib monotherapy has rarely been reported. The aim of this study was to assess whether regorafenib combined with a PD-1 antibody is superior to regorafenib monotherapy as third-line treatment for MSS mCRC. MethodsPatients with MSS mCRC who received regorafenib combined with a PD-1 antibody or regorafenib monotherapy as third-line treatment were eligible for inclusion. ResultsIn total, 179 patients were enrolled, of which 95 administered regorafenib combined with a PD-1 antibody and 84 administered regorafenib monotherapy. Overall, patients who administered regorafenib combined with a PD-1 antibody had similar progression-free survival (PFS) outcomes as those on regorafenib monotherapy (median PFS was 2.4 months and 1.9 months, respectively, P = 0.086). The administration of regorafenib combined with a PD-1 antibody showed signi cantly longer PFS than regorafenib monotherapy in both male (5.2 months vs. 2.4 months, P = 0.001) and female (3.9 months vs. 1.8 months, P = 0.037) patients without liver metastasis. Unexpectedly, female patients with liver metastasis who administered regorafenib combined with a PD-1 antibody showed inferior PFS outcomes than those who administered regorafenib monotherapy (1.8 months vs. 2.0 months, P = 0.030). ConclusionLiver metastasis and gender were predictors of survival bene t following the addition of a PD-1 antibody to regorafenib in patients with MSS mCRC.