KLF12 as a potential biomarker for lateral pelvic lymph node metastases in advanced rectal cancer.

Rectal cancer accounts for approximately 40% of colorectal cancer cases, and lateral pelvic lymph node (LPLN) metastasis in rectal cancer significantly increases the local recurrence rate. Despite its clinical significance, studies on the molecular biology of LPLN metastasis are relatively scarce. In this study, we aimed to elucidate the underlying mechanisms by identifying hub regulatory genes in LPLN tissues and analyzing differentially expressed genes shared between tumor and pericarcinomatous tissues within our clinical cohort. To investigate the biological functions of these hub regulatory genes, we performed GSEA, GO, and KEGG pathway analyses on mRNA-Seq data. Among the identified hub genes, KLF12 emerged as a pivotal regulatory gene in rectal cancer. We further explored its clinical relevance and biological function. Our findings, validated using public databases, clinical cohort data, and immunohistochemistry (IHC), identified KLF12 as a specific marker for LPLN. Additionally, KLF12 expression exhibited a strong correlation with disease-free survival (DFS). According to clinical data, significant differences in KLF12 expression exist between groups based on factors such as age, gender, tumor location, pathological N stage, and postoperative tumor residue. Both treatment outcomes (DFS) and receiver operating characteristic curves (AUCs) were significantly associated with KLF12 expression. Furthermore, KLF12 demonstrated a strong association with immune cell infiltration, immune checkpoint expression, and immunophenoscore (IPS), indicating its potential regulatory role in immunotherapy. Functional molecular experiments revealed that KLF12 overexpression inhibited the proliferation, migration, and invasion of SW620 cells. In conclusion, leveraging mRNA-Seq data, TCGA database analysis, immune infiltration data, and biological function assessments, we confirmed that KLF12 could serve as an effective predictive marker and potential therapeutic target for LPLN metastasis. These findings suggest that KLF12 may be instrumental in assessing predictive risk and identifying novel therapeutic targets for patients with rectal cancer.