Association of LAMA3 expression with perineural invasion and chemoresistance in pancreatic ductal adenocarcinoma.

[BACKGROUND] Pancreatic ductal adenocarcinoma (PDAC) is a common type of malignant tumor of the pancreas with high aggressiveness and low prognosis. Due to the insidious early symptoms of pancreatic adenocarcinoma, patients are mostly diagnosed at advanced stages with a high incidence of nerve invasion. With the rapid development of precision medicine, studying the molecular mechanisms behind PDAC can help its diagnosis and treatment, which is conducive to improving the prognosis of PDAC patients.

[OBJECTIVE] To explore the correlation between LAMA3 expression and nerve invasion in pancreatic ductal adenocarcinoma tissues.

[METHODS] Ninety-four patients with pathologically confirmed diagnosis of PDAC in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Anhui Medical University were retrospectively collected from January 2023 to December 2023, and the patients' clinicopathological data were collected and followed up for 5 months. Immunohistochemical staining was applied to detect the expression level of LAMA3 in cancer tissues, and paraneoplastic tissues were used as controls to compare the differences in the expression level of LAMA3. The Kaplan-Meier method was used to draw the survival curves, and the Cox proportional risk regression model was set up to analyze the correlation between the expression of LAMA3 and the nerve invasion.

[RESULTS] Immunohistochemical staining results showed that LAMA3 was mainly expressed in the cytoplasm and appeared as yellow to brown granules.The positive expression rate of LAMA3 in PDAC cancer tissues was 63.83% (60/94), which was significantly higher than that in paracancerous tissues (12.77%, 12/84), and the difference between the two groups was statistically significant (x = 51.862, P < 0.001). Patients were categorized into nerve invasion negative (n = 30) and nerve invasion positive (n = 64) according to the presence or absence of nerve invasion.Cox proportional analysis regression results showed that the LAMA3 expression level was an independent risk factor affecting the occurrence of nerve invasion in PDAC patients. Survival analysis showed that median OS was significantly lower in patients with high LAMA3 expression and development of vascular invasion than in patients with low LAMA3 expression and no vascular invasion (P < 0.001); in TNM staging, median OS was significantly lower in patients with stage II than in patients with stage I (P < 0.001).

[CONCLUSION] LAMA3 expression level is an independent risk factor for the occurrence of neuroinvasion in PDAC patients; LAMA3 expression level, TNM staging and prognosis of PDAC patients are correlated; LAMA3 expression level may serve as a valuable biomarker for the occurrence, development, and prediction of prognosis of patients with PDAC, and also as a potential therapeutic target for PDAC patients.