HIF-1α and PD-L1 as Predictive Efficacy Marker for Neoadjuvant Chemoradiotherapy in Rectal Cancer.

[BACKGROUND] NCRT is a standard preoperative treatment for locally advanced RC with variable efficacy. This prospective cohort study explored HIF-1α and PD-L1 expression in RC and their impact on NCRT efficacy to provide a theoretical basis for effective predictive indicators.

[METHODS] Patients with locally advanced rectal cancer (n = 128) (cT3/T4-N0 or cTany-N1/N2) were prospectively enrolled. General clinical data were collected. Preoperative tumor and adjacent non-tumor tissues were obtained via pre-treatment biopsy, and HIF-1α/PD-L1 expression was detected by qRT-PCR. All patients underwent radical surgery after NCRT, with efficacy evaluated by pTRG. ROC analysis assessed the predictive value of HIF-1α/PD-L1 for NCRT response. Logistic regression analyzed HIF-1α/PD-L1 independent association with NCRT efficacy. The 5-year follow-up recorded survival/recurrence; Kaplan-Meier analyzed DFS/OS, and COX regression explored the independent correlation between HIF-1α/PD-L1 mRNA levels and post-NCRT DFS/OS.

[RESULTS] HIF-1α and PD-L1 were highly expressed in tumor tissues, with higher levels in NCRT-insensitive patients. Combined HIF-1α and PD-L1 showed better AUC for predicting NCRT insensitivity than either alone (AUC = 0.706, sensitivity = 63.24%, specificity = 73.33%). For each 1-unit increase in HIF-1α and PD-L1, the risk of recurrence in patients increased by 1.567-fold (p = 0.001, HR = 1.567, 95% CI = 1.216-2.018), and the risk of death increased by 1.725-fold (p = 0.000, HR = 1.725, 95% CI = 1.354-2.200).

[CONCLUSION] HIF-1α and PD-L1 expression can serve as reliable indicators for predicting NCRT efficacy and poor prognosis in RC patients.