Introduction: Therapists must select the best treatment appropriate for the patient. We conducted clinical trials to identify potential human leukocyte antigens (HLAs) in response to cancer treatment.

Patients and Methods: We recruited participants (n = 2,035) who had undergone resection surgery (RS) and HLA testing, had a confirmed family history (FH) of cancer, and received polysaccharide-K (PSK), fluoropyrimidine antimetabolites (FA), mitomycin C (MMC), and their combination therapies as a postoperative adjuvant therapy (PAT). We classified good or poor survival peptide groups matching the human endogenous retrovirus genes (HERVs) according to therapies and FH groups. Subsequently, we assessed the HLA incidence of peptide groups between patients with good and poor survival. We investigated the overall survival of these HLA antigens. Similarly, FH groups and sex differences FH evaluated the relation to HLA-A-locus-based HLAs.

Results: We predicted how the HLAs of an individual patient responded to treatments such as RS only, FA, PSK, MMC, and their combination (MFPSK). In addition, we investigated how the HLA antigens of an individual patient did not respond to RS only. In particular, positive for the HLA-A2 related to good response to FA, PSK, MMC, and MFPSK, while poor response to RS only.

Conclusion: We confirmed the clinical significance of HLA testing; however, this depended on the association with peptides, sex, and their FH. These associations enabled the prediction of treatment response, in particular, the response or non-response to RS only, which was never achieved even by other genomic sciences.

Introduction: The albumin-to-globulin ratio (AGR) has been extensively studied as a predictor of the clinical outcomes of various tumors including gastric cancer (GC). Meanwhile, the predictive performance of the albumin-lymphocyte-globulin-C-reactive protein (ALGC) index has not yet been examined for GC. We investigated the clinical relevance of the preoperative ALGC index in patients undergoing curative surgery for GC, alongside the AGR and five other well-established inflammatory/nutritional parameters.

Methods: We included 157 consecutive patients undergoing R0/R1 gastrectomy for GC. We retrospectively assessed the associations of these preoperative laboratory data indices with clinicopathological characteristics, postoperative complications and survival outcomes, employing receiver operating characteristic (ROC) curves, logistic regression and the Cox proportional hazards model.

Results: With ROC curves, the preoperative ALGC index had the largest area under the curve among seven examined indices. The preoperative ALGC index was significantly related to postoperative complications and the association remained independent even in a multivariate model (odds ratio 0.847 per 1-unit increase, 95% confidence interval 0.694-0.979, P = 0.021), while the other six indices did not. In univariate survival analyses, the preoperative ALGC index showed significant correlations with both overall and relapse-free survivals. There were, however, no independent relationships of the ALGC index with survival outcomes on multivariate analysis.

Conclusions: A lower preoperative ALGC index independently predicted adverse short-term outcomes following gastrectomy for GC, demonstrating superior predictive accuracy compared to other established parameters. Risk stratification using the ALGC index may help identify patients at increased risk of postoperative morbidity and thereby support individualized treatment strategies.

Introduction: We previously reported that the certain peptides decrease after age ≥65 years. To evaluate their clinical significance, we assessed the association between natural aging and peptides matching human endogenous retrovirus genes.

Patients and Methods: We recruited participants (n = 2,035) from an earlier report who were classified into the following peptide groups (PGs) according to age: Age80PG, Age49PG, Age65PG, Age65-79PG, and Age65-79_AP_VpuPG. Next, we examined the frequency of human leucocyte antigens (HLAs) in PGs of HLA groups (HGs) and evaluated the survival outcomes in both PGs and HGs. We assessed whether HLAs could predict the treatment response. Some patients were examined for peripheral T-cell subpopulations at baseline and one year after surgery.

Results: Most patients belonged to PGs which increased frequency among patients age ≥80 years. The Age80PGlowHGs with a high frequency of PGs, low frequency of HLAs, and age ≥80 years showed no significant increase of CD8+ cells at one year after surgery, which resulted in detrimental survival outcomes, while the Age65PGhighHG cohort, with a low frequency of PGs, high frequency of HLAs, and age ≥65 years, presented significantly increased CD8+ cells at one year after surgery, which resulted beneficial survival outcomes. We predicted that although the overall Age80PGlowHG cohort harboring HLA-A33, or -B44, or -B56, or -DR13, would show detrimental survival outcomes, family history (+) females would respond positively to fluoropyrimidine antimetabolites therapy.

Conclusion: Our findings offer new insights into the balance between beneficial and detrimental effects of natural aging on cancer therapy.