The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2′-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01–1.98, p = 0.04) and 1.60 (95% CI: 1.12–2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage Ⅲ/Ⅳ) were 1.51 (95% CI: 1.02–2.22, p = 0.04) and 1.64 (95% CI: 1.09–2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.

The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification for precise prediction. HSP60 expression increased with differentiation and p53 mutations in patients. However, compared to patients with high HSP60 expression, patients with low HSP60 expression had event-free survival and disease-specific survival hazard ratios (HRs) of 1.42 and 1.69, respectively. Moreover, when the survival rate was analyzed by combining TNM classification and HSP60 expression, the prognosis was poor, particularly when HSP60 expression was low in the late/advanced stage. This pattern was also observed with HSP family D member 1, HSPD1, the gene that encodes HSP60. Low HSPD1 expression was linked to lower overall survival and relapse-free survival rates, with HRs of 1.80 and 1.87, respectively. When TNM classification and HSPD1 expression were considered, CRC patients with low HSPD1 expression and advanced malignancy had a poorer prognosis than those with high HSPD1 expression. Thus, HSPD1/HSP60 can be a useful biomarker for a sophisticated survival prediction in late- and advanced-stage CRC, allowing the design of individualized treatment strategies.

“Biomarker-driven targeted therapy,” the practice of tailoring patients’ treatment to the expression/activity levels of disease-specific genes/proteins, remains challenging. For example, while the anti-ERBB2 monoclonal antibody, trastuzumab, was first developed using well-characterized, diverse in vitro breast cancer models (and is now a standard adjuvant therapy for ERBB2-positive breast cancer patients), trastuzumab approval for ERBB2-positive gastric cancer was largely based on preclinical studies of a single cell line, NCI-N87. Ensuing clinical trials revealed only modest patient efficacy, and many ERBB2-positive gastric cancer (GC) patients failed to respond at all (i.e., were inherently recalcitrant), or succumbed to acquired resistance. To assess mechanisms underlying GC insensitivity to ERBB2 therapies, we established a diverse panel of GC cells, differing in ERBB2 expression levels, for comprehensive in vitro and in vivo characterization. For higher throughput assays of ERBB2 DNA and protein levels, we compared the concordance of various laboratory quantification methods, including those of in vitro and in vivo genetic anomalies (FISH and SISH) and xenograft protein expression (Western blot vs. IHC), of both cell and xenograft (tissue-sectioned) microarrays. The biomarker assessment methods strongly agreed, as did correlation between RNA and protein expression. However, although ERBB2 genomic anomalies showed good in vitro vs. in vivo correlation, we observed striking differences in protein expression between cultured cells and mouse xenografts (even within the same GC cell type). Via our unique pathway analysis, we delineated a signaling network, in addition to specific pathways/biological processes, emanating from the ERBB2 signaling cascade, as a potential useful target of clinical treatment. Integrated analysis of public data from gastric tumors revealed frequent (10 – 20 %) amplification of the genes NFKBIE, PTK2, and PIK3CA, each of which resides in an ERBB2-derived subpathway network. Our comprehensive bioinformatics analyses of highly heterogeneous cancer cells, combined with tumor “omics” profiles, can optimally characterize the expression patterns and activity of specific tumor biomarkers. Subsequent in vitro and in vivo validation, of specific disease biomarkers (using multiple methodologies), can improve prediction of patient stratification according to drug response or nonresponse.

Tamoxifen is widely used in breast cancer treatment, but its effects on vaginal microbiome remain poorly understood. This prospective longitudinal pilot study explored vaginal microbiota profiles and quality-of-life parameters in women receiving tamoxifen for breast cancer in Seoul, South Korea (2023–2024). Eleven women initiating tamoxifen therapy were enrolled. Vaginal swabs were collected at baseline (V0) and 6 months (V6). Microbiota was profiled using 16 S rRNA gene sequencing. Quality of life was assessed using the 11-item Menopause Rating Scale. Participants were stratified by baseline colonization patterns. Overall community composition did not show a significant shift between baseline and 6 months. In the full-cohort taxa-level paired analysis, Gardnerella vaginalis ( G. vaginalis ) showed a nominal, non-FDR-significant increase from baseline to 6 months, and no taxon remained significant after multiple-comparison correction. A negative correlation was observed between G. vaginalis and Lactobacillus iners ( L. iners ) (ρ = −0.6, raw P < 0.01, FDR q < 0.05). Among participants with baseline G. vaginalis detection, 4 of 5 showed increased relative abundance at 6 months, although the confidence interval was wide. G. vaginalis abundance was associated with worse sexual-function-related quality-of-life scores in exploratory analyses, but item-level MRS comparisons did not remain significant after correction for multiple testing. In this small hypothesis-generating pilot cohort, women receiving tamoxifen showed largely stable overall vaginal community composition over 6 months, with an exploratory signal of G. vaginalis expansion among participants colonized at baseline. These findings should be interpreted cautiously given the small sample size, absence of a control group, treatment heterogeneity, and post hoc subgroup analysis, and require validation in larger controlled cohorts.