Limited studies have assessed the associations of pretreatment serum glutamine level with clinicopathological characteristics and prognosis of colorectal cancer (CRC) patients. This study focuses on clarifying the clinical significance of baseline serum glutamine level in CRC patients. We retrospectively examine 123 patients with newly diagnosed CRC between 2009 and 2011. The associations of pretreatment serum glutamine level with clinicopathological characteristics, proinflammatory cytokines, overall survival (OS), and progression-free survival (PFS) were analyzed. We executed univariate and multivariate analyses to assess the associations between serum glutamine level and clinicopathological variables able to predict survival. Low glutamine levels were associated with older age, advanced stage, decreased albumin levels, elevated carcinoembryonic antigen levels, higher C-reactive protein levels, higher modified Glasgow prognostic scores, and higher proinflammatory cytokine levels. Furthermore, patients with low glutamine levels had poorer OS and PFS than those with high glutamine levels (p < 0.001 for both). In multivariate analysis, pretreatment glutamine level independently predicted OS (p = 0.016) and PFS (p = 0.037) in CRC patients. Pretreatment serum glutamine level constitutes an independent prognostic marker to predict survival and progression in CRC patients.

Study on the impact of pretreatment malnutrition on treatment outcomes in locally advanced head and neck cancer (LAHNC) patients is still lacking. We prospectively collected various malnutrition assessment methods including nutrition indexes, inflammatory biomarkers, and lean body mass index (LBMI) data before treatments. The one year mortality rate was assessed, and the factors associated with this outcome were investigated. Furthermore, the association between malnutrition assessment methods was examined. A total of 113 patients were enrolled. By prognostic stratification based on the prognostic nutritional index (PNI) and platelet-to-lymphocyte ratio (PLR) combination, the low PNI/high PLR group had highest and the high PNI/low PLR group had the lowest mortality rate. Furthermore, the PNI was positively correlated with the LBMI, and the PLR was inversely correlated with the LBMI. PNI and PLR were found to be independent prognostic factors of one year mortality and also associated with the loss of muscle.

Background: This study investigates whether the appendicular skeletal muscle index (ASMI) was an independent prognostic predictor for patients with locally advanced head and neck cancer (LAHNC) receiving concurrent chemoradiotherapy (CCRT) and whether there were any differences in lean mass loss in different body regions during CCRT. Methods: In this prospective study, we analyzed the clinicopathological variables and the total body composition data before and after treatment. The factors associated with the 2-year recurrence-free survival rate (RFSR) were analyzed via logistic regression analysis. Results: A total of 98 patients were eligible for analysis. The body weight, body mass index, and all parameters of body composition significantly decreased after CCRT. The pretreatment ASMI was the only independent prognostic factor for predicting the 2-year RFSR (hazard ratio, 0.235; 95% confidence interval, 0.062–0.885; p = 0.030). There was at least 5% reduction in total lean and fat mass (p < 0.001); however, the highest lean mass loss was observed in the arms (9.5%), followed by the legs (7.2%), hips (7.1%), waist (4.7%), and trunk (3.6%). Conclusions: The pretreatment ASMI was the only independent prognostic predictor for the 2-year RFSR of LAHNC patients undergoing CCRT. Asynchronous loss of lean mass may be observed in different body parts after CCRT.

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC (n = 69) and NOCC (n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

Although treatments for HNSCC have improved, the cancer is still challenging because many patients tend to develop the disease again nearby and often have poor recovery. Since drug-tolerant persister (DTP) cells display a wide range of types and unique genetic characteristics, nonhormonal endocrine therapies, including chemotherapy, targeted therapy and immunotherapy, are ineffective in eliminating these cells. DTP cells evade elimination by entering a reversible dormant state characterized by altered metabolism, enhanced DNA repair capacity, and modified immune escape mechanisms, all of which promote the cells' survival and treatment failure. Platinum-based chemotherapy, widely prescribed for HNSCC, reduces tumor size but fails to confer long-term benefits because of the strong treatment resistance of DTP cells. These cells also exhibit resistance to tyrosine kinase inhibitors by activating alternative signaling pathways. Alternative survival pathways are also activated in DTP cells when targeted therapies such as those using epidermal growth factor receptor inhibitors are used. Although programmed death 1/programmed death ligand 1 inhibitors are exciting new treatments, their effect is hampered by DTP cells that affect the immune system. This review examines the ways DTP cells make HNSCC tumor cells resistant to treatment by looking at metabolic reprogramming, DNA methylation alterations and the microenvironment of the tumor. This review further explores strategies for targeting metabolic dependencies, inhibiting DNA repair, and combining therapeutic approaches, all of which can mitigate DTP cell-mediated recurrence. Advancing strategies that specifically target DTP cells could enhance HNSCC management by reducing recurrence and improving overall prognosis.

Building on our previous identification of TXNRD1 and RHOJ as mediators of immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC), this study investigates the role of RHOJ in regulating endothelial markers and signaling pathways in drug-tolerant persister (DTP) cells, as well as its contribution to immune suppression within the resistant tumor microenvironment. We examined the role of RHOJ in regulating tumor-associated macrophage polarization and enhancing M1 antitumor activity and evaluated the therapeutic potential of targeting the RHOJ/Rho kinase axis in an HNSCC DTP mouse model. RHOJ expression was significantly upregulated in HNSCC DTP cells. RHOJ contributes to chemoresistance by increasing oxidative stress and initiating the DNA damage response. RNA sequencing revealed that the IPO9/EpCAM signaling pathway positively regulates RHOJ expression. Knockdown of RHOJ with shRNA suppressed HNSCC DTP cell migration and downregulated IPO9/EpCAM signaling. Gene enrichment analysis revealed high RHOJ expression in tumor-associated endothelial cells. Treatment with the RHOJ-dependent F-actin inhibitor Latrunculin B (HY-101,848) impaired actin polymerization and increased the chemosensitivity of HNSCC DTP cells. Silencing RHOJ inhibited M2 tumor-associated macrophage activation. RHOJ overexpression promoted M2 macrophage proliferation. RHOJ plays a critical role in modulating immunosuppressive signaling in both tumor and endothelial cells. RHOJ promotes the function of tumor-associated endothelial cells and drives EMT through its interaction with the IPO9/EpCAM signaling pathway, thereby increasing cell survival and drug resistance. Additionally, RHOJ may limit immune cell infiltration into the tumor core and promote immune evasion by contributing to vascular abnormalities and impaired barrier function.